[Senate Hearing 112-934]
[From the U.S. Government Publishing Office]
S. Hrg. 112-934
PHARMACY COMPOUNDING: IMPLICATIONS OF THE 2012 MENINGITIS OUTBREAK
=======================================================================
HEARING
OF THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
UNITED STATES SENATE
ONE HUNDRED TWELFTH CONGRESS
SECOND SESSION
ON
EXAMINING PHARMACY COMPOUNDING, FOCUSING ON IMPLICATIONS OF THE 2012
MENINGITIS OUTBREAK
__________
NOVEMBER 15, 2012
__________
Printed for the use of the Committee on Health, Education, Labor, and
Pensions
Available via the World Wide Web: http://www.gpo.gov/fdsys/
______
U.S. GOVERNMENT PUBLISHING OFFICE
94-198 PDF WASHINGTON : 2015
-----------------------------------------------------------------------
For sale by the Superintendent of Documents, U.S. Government Publishing
Office Internet: bookstore.gpo.gov Phone: toll free (866) 512-1800;
DC area (202) 512-1800 Fax: (202) 512-2104 Mail: Stop IDCC,
Washington, DC 20402-0001
COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
TOM HARKIN, Iowa, Chairman
BARBARA A. MIKULSKI, Maryland
JEFF BINGAMAN, New Mexico
PATTY MURRAY, Washington
BERNARD SANDERS (I), Vermont
ROBERT P. CASEY, JR., Pennsylvania
KAY R. HAGAN, North Carolina
JEFF MERKLEY, Oregon
AL FRANKEN, Minnesota
MICHAEL F. BENNET, Colorado
SHELDON WHITEHOUSE, Rhode Island
RICHARD BLUMENTHAL, Connecticut
MICHAEL B. ENZI, Wyoming
LAMAR ALEXANDER, Tennessee
RICHARD BURR, North Carolina
JOHNNY ISAKSON, Georgia
RAND PAUL, Kentucky
ORRIN G. HATCH, Utah
JOHN McCAIN, Arizona
PAT ROBERTS, Kansas
LISA MURKOWSKI, Alaska
MARK KIRK, Illinois
Pamela J. Smith, Staff Director, Chief Counsel
Lauren McFerran, Deputy Staff Director
Frank Macchiarola, Republican Staff Director
(ii)
C O N T E N T S
__________
STATEMENTS
THURSDAY, NOVEMBER 15, 2012
Page
Committee Members
Harkin, Hon. Tom, Chairman, Committee on Health, Education,
Labor, and Pensions, opening statement......................... 1
Prepared statement........................................... 2
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming,
opening statement.............................................. 4
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas....... 6
Mikulski, Hon. Barbara A., a U.S. Senator from the State of
Maryland....................................................... 34
Alexander, Hon. Lamar, a U.S. Senator from the State of Tennessee 36
Hagan, Hon. Kay R., a U.S. Senator from the State of North
Carolina....................................................... 39
Blumenthal, Hon. Richard, a U.S. Senator from the State of
Connecticut.................................................... 41
Bennet, Hon. Michael F., a U.S. Senator from the State of
Colorado....................................................... 43
Witnesses--Panel I
Bell, Beth, M.D., MPH, Director, National Center for Emerging and
Zoonotic Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA........................................ 8
Prepared statement........................................... 10
Hamburg, Margaret A., M.D., Commissioner, Food and Drug
Administration, Washington, DC................................. 16
Prepared statement........................................... 18
Smith, Lauren, M.D., MPH, Interim Commissioner, Department of
Public Health, Boston, MA...................................... 23
Prepared statement........................................... 25
Witness--Panel II
Cadden, Barry, Owner and Director of Pharmacy, New England
Compunding Center, Framingham, MA--(Mr. Cadden declined to
appear)
Witnesses--Panel III
Kainer, Marion, M.D., MPH, FRACP, Director, Healthcare Associated
Infections & Antimicrobial Resistance Program, Tennessee
Department of Health, Nashville, TN............................ 55
Prepared statement........................................... 57
Miller, David G., R.Ph., Executive Vice President and CEO,
International Academy of Compounding Pharmacists, Missouri
City, TX....................................................... 65
Prepared statement........................................... 66
Thompson, Kasey K., Pharm.D., M.S., B.S., Vice President, Office
of Policy, Planning and Communications, American Society of
Health-System Pharmacists, Bethesda, MD........................ 74
Prepared statement........................................... 76
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
Senator Casey................................................ 87
(iii)
John J. Dreyzehner, M.D., MPH, FACOEM, Commissioner,
Tennessee Department of Health, Nashville, TN.............. 88
Andrew C. Holt, Pharm.D. Executive Director, Tennessee Board
of Pharmacy, Nashville, TN................................. 90
Craig Becker, President, Tennessee Hospital Association,
Nashville, TN.............................................. 92
Baeteena M. Black, D.Ph., Executive Director, Tennessee
Pharmacists Association (TPA), Nashville, TN............... 94
Wiley Robinson, M.D., FHM, President, Tennessee Medical
Association (TMA), Nashville, TN........................... 97
Response by Lauren A. Smith, M.D., MPH, to questions of the
HELP Committee............................................. 98
Response by Marion Kainer to question of Senator Whitehouse.. 109
Response by David G. Miller, R.Ph., to questions of:
Senator Enzi............................................. 110
Senator Casey............................................ 110
Senator Franken.......................................... 112
Response by Kasey K. Thompson to questions of:
Senator Enzi............................................. 117
Senator Casey............................................ 119
Senator Franken.......................................... 120
PHARMACY COMPOUNDING: IMPLICATIONS OF THE 2012 MENINGITIS OUTBREAK
----------
THURSDAY, NOVEMBER 15, 2012
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Washington, DC.
The committee met, pursuant to notice, at 9:53 a.m., in
room SD-106, Dirksen Senate Office Building, Hon. Tom Harkin,
chairman of the committee, presiding.
Present: Senators Harkin, Enzi, Mikulski, Casey, Hagan,
Merkley, Franken, Bennet, Blumenthal, Alexander, and Roberts.
Opening Statement of Senator Harkin
The Chairman. The Senate Committee on Health, Education,
Labor, and Pensions will please come to order.
We're meeting here today to better understand what caused
one of the worst public health crises this country has
experienced in recent years, the meningitis outbreak that has
claimed the lives of 32 Americans and sickened at least 461
people. While those affected grapple with side effects and
complications related to treatment, thousands more are waiting
to see if they become ill. This outbreak has been traced back
to pharmaceuticals produced at the New England Compounding
Center in Framingham, MA, where it is now clear the owners and
managers demonstrated a complete disregard for basic procedures
to ensure that the products they were manufacturing were
sterile.
The real question we will seek to answer today is: How
could this have happened? How could 17,000 doses of a product
so contaminated that, upon recall, black particles were visible
to the naked eye in some of the samples, have been shipped to
23 States? How could a pharmacy that the FDA had described in
2003 as posing, and I quote,
`` . . . the potential for serious public health
consequences if the compounding practices, in
particular, those relating to specific sterile
products, are not improved . . . ''
How could they have been then licensed to ship drugs to 45
different States?
As we have learned over the course of our committee
inquiry, NECC's shortcomings were well-documented. The FDA and
the Massachusetts Board of Pharmacy repeatedly found
significant deficiencies in their operations, including the
suspected destruction of documents and contaminated lots;
findings of bacterial contamination in compounded medications;
findings of sterile injectable products that were both too weak
or too strong in potency; and repeated complaints about the
sale of compounded drugs without a patient-specific
prescription in direct violation of State and Federal law.
Yet, despite the abundance of documentation, neither the
Massachusetts Board nor the FDA appears to have taken the
necessary steps to protect the public from these products.
I will dispense with the rest of my statement, and I will
submit it in its entirety for the record.
[The prepared statement of Senator Harkin follows:]
Prepared Statement of Senator Harkin
The committee will come to order. We are meeting here today
to better understand what caused one of the worst public health
crises this country has experienced in recent years: the
meningitis outbreak that has claimed the lives of 32 Americans
and sickened at least 461 people.
While those affected grapple with side effects and
complications related to treatment, thousands more are waiting
to see if they become ill. This outbreak has been traced back
to pharmaceuticals produced at the New England Compounding
Company in Framingham, Massachusetts, where owners and managers
demonstrated a complete disregard for basic procedures to
ensure that the products they were manufacturing were sterile.
The question we will seek to answer today is: how could
this have happened? How could 17,000 doses of a product so
contaminated that upon recall, black particles were visible to
the naked eye, have been shipped to 23 States? How could a
pharmacy that the FDA had described in 2003 as posing,
`` . . . the potential for serious public health
consequences if [the] compounding practices, in
particular those relating to specific sterile products
are not improved, . . . ''
have been licensed to ship drugs to 45 different States?
As we have learned over the course of our committee
inquiry, NECC's shortcomings were well-documented. The FDA and
the Massachusetts Board of Pharmacy repeatedly found
significant deficiencies in NECC's operations, including the
suspected destruction of documents and contaminated lots;
findings of bacterial contamination in compounded medications;
findings of sterile injectable products that were both too weak
or too strong in potency; and repeated complaints about the
sale of compounded drugs without a patient-specific
prescription, in direct violation of State and Federal law. And
yet, despite the abundance of documentation, neither the
Massachusetts Board nor the FDA appears to have taken the
necessary steps to protect the public from these products.
Equally troubling is that fact that, when the owners and
managers of NECC sought a license for a separate company,
Ameridose, to compound drugs on scale perhaps 10 times the size
of NECC, these same State and Federal regulators granted that
license. They did so without referencing the checkered history
of NECC, even though Ameridose would supply hospitals across
the country under contract with the largest group purchasing
organization in the United States. How could that history not
been deemed relevant? How could NECC's owners have been allowed
to expand their operations, in light of their history? These
are questions I am hoping to answer today.
In the face of such a tragedy it is natural to want to take
action. And we will. This committee has a demonstrated ability
to work to find bipartisan solutions that will take into
consideration the needs of all stakeholders. The hearing today
will explore not just what happened, but it will begin to help
us determine how to prevent similar outbreaks in the future.
What is important to remember, however, is that drug
compounding is essential and that most pharmacies that compound
do so on a vastly smaller scale than NECC. We need to ensure
that these pharmacists can continue to compound without a
drastic increase in overhead.
We also know that to address drug shortages, compounding is
occurring both in hospitals and in pharmacies to replenish
supply of previously available drugs. Indeed, in the case of
methylprednisolone acetate, the drug at issue in the outbreak,
two manufacturers had ceased producing the drug in the last 2
years.
We know compounding is critical, and that the need for
large scale compounding is increasing. But we do not know where
or how much large-scale drug compounding is being conducted, or
if these companies are compounding drugs in accordance with
best practice standards. More importantly, we have no way of
knowing which facilities are not in compliance. This is a
problem and indicates to me the need for better Federal
regulation in this area.
As a committee, we will work together to identify and plug
any gaps in our regulators' authority. We want to ensure that
any pharmacy that takes the kinds of risks with patient lives
that NECC did will be shut down long before more patients get
hurt. The only good that can come from a tragic situation like
this outbreak is the momentum to make changes to prevent it
from ever happening again. I look forward to hearing the
thoughts of the panel on this topic and I promise the other
members of this committee who I know have a history on this
issue to working together with you to ensure that a problem
like this cannot occur again.
In our first panel, we'll hear from Dr. Beth Bell of the
Centers for Disease Control and Prevention about the public
health impact of the meningitis outbreak and CDC's role in
responding to it. Dr. Peggy Hamburg of FDA and Dr. Lauren Smith
of the Massachusetts Department of Public Health will talk to
us about the role of their agencies in regulating compounding
pharmacies in general and in investigating NECC specifically.
And we'll ask them about their views on what we can do to
prevent future crises.
We invited the manager and co-owner of the New England
Compounding Center, Mr. Barry Cadden, to appear on our second
panel. We were informed by Mr. Cadden's attorney that he would
decline to voluntarily appear, and if compelled to appear,
would invoke his Fifth Amendment right against self-
incrimination and refuse to answer our questions. I am
disappointed by his failure to appear, but frankly, I believe
this committee has amply demonstrated the extensive failures of
Mr. Cadden and NECC, as the record of this hearing will make
clear.
On our third panel, we will talk to the physician whose
critical work led to the initial identification of the outbreak
and who ably worked with CDC to isolate NECC products as the
source of the meningitis infections, Dr. Marion Kainer of the
Tennessee Department of Health. We'll also talk with David
Miller from the International Academy of Compounding
Pharmacists and Dr. Kasey Thompson of the American Society of
Health-System Pharmacists about the use of compounding in
medical care, and the measures needed to ensure that compounded
drugs are safe.
Before we begin, I'd like to submit to the record the
documents that we have received from NECC, FDA, and
Massachusetts in response to our investigatory letters.
The Chairman. But before we begin, I'd like to submit for
the record the documents that we have received from NECC, the
FDA, and Massachusetts in response to our investigatory
letters. Without objection, they'll be submitted for the
record.
[Editor's Note: Due to the large volume of documents and
the high cost of printing, the information referred to is
maintained in the committee file.]
And with that, I'll yield to Senator Enzi.
Opening Statement of Senator Enzi
Senator Enzi. Thank you, Mr. Chairman.
Thirty-two Americans have died, out of 461 total, sickened
after receiving contaminated steroid injections produced by the
New England Compounding Center, or NECC. Additionally,
approximately 14,000 patients in 23 States have been exposed to
potentially contaminated injections produced by the same
pharmacy.
This case represents a catastrophic failure by the
regulatory agencies that are charged with protecting patients
from unsafe drugs. Such a failure is unacceptable, and we're
going to examine what happened in order to determine what needs
to be done to prevent it from reoccurring.
The compounding pharmacy that caused these patients' deaths
and illnesses has a long history of problems with product
safety and compliance with State regulations. These problems
began almost as soon as NECC first received its pharmacy
license in the late 1990's, when complaints began to be made
about the sterility of the products and its practices around
the requirement for individual patient prescriptions.
Both the FDA and Massachusetts Board of Pharmacy became
aware of the problems with NECC over a decade ago. They jointly
inspected NECC's facility and held multiple meetings about the
problems they discovered. The Massachusetts Board entered into
a consent decree with NECC in 2006. Later that year, FDA also
issued a warning letter to NECC.
Despite the multiple warnings, State and Federal regulators
failed to continue to monitor NECC and take the steps that
could have prevented the current situation. In particular, the
Massachusetts Board should have known from its numerous
inspections of NECC's facility that it was operating a large-
scale drug manufacturing operation. That information, coupled
with repeated complaints highlighting NECC's pattern of failing
to require valid prescriptions for specific patients, clearly
contravened Massachusetts regulatory requirements for
compounding pharmacies.
Even after receiving multiple complaints about the
sterility and safety of drugs compounded by NECC, there is no
evidence that the Board made any effort to even followup and
inspect NECC's facility from 2006 until 2011. State boards of
pharmacy have explicit authority over the practice of pharmacy,
including compounding products for individual patients. States
like Massachusetts also have clear and unequivocal authority to
inspect, suspend, and revoke pharmacy licenses.
While there have been litigation and conflicting court
decisions around Federal legislation enacted in 1997 to
differentiate between compounded and manufactured products,
this ambiguity alone cannot be blamed for this tragedy. FDA can
inspect any facility that manufactures, processes, packs, or
holds products for interstate commerce and has authority over
unapproved new drugs in interstate commerce. FDA also has the
ability to take action against misbranded or adulterated
products.
NECC was clearly operating outside its pharmacy license in
violating State laws requiring individual prescriptions. NECC
also looked like it was operating as a large-scale drug
manufacturer, pretending to be a pharmacy in order to avoid FDA
regulation. In every warning letter and legal brief the Food
and Drug Administration has ever issued concerning this very
type of conduct, including a 2006 warning letter to NECC, the
agency said it had clear authority to regulate this very type
of conduct.
I hope today we can find out why these State and Federal
authorities were not used to prevent this tragedy. The
committee is and will continue to investigate NECC's conduct
and the oversight of both FDA and the Massachusetts Board of
Pharmacy. We've sent letters to FDA, the Massachusetts Board,
and NECC. We've received over 10,000 pages of documents, which
show NECC has a history of not complying with State and Federal
law. We expect to receive more documents in the coming weeks
and will leave no stone unturned.
I want to take a moment to recognize the longstanding
interest of my colleagues, Senators Roberts and Burr, regarding
pharmacy compounding. They've been leaders in this area since
the late 1990s and released a draft of pharmacy compounding
legislation with former HELP Committee Chairman Kennedy in
2007.
Many other members of the HELP Committee also have a strong
interest in this matter. Senator Alexander's home State of
Tennessee has been hit particularly hard by the current
outbreak. I know that Senators Franken and Blumenthal have
strong views. Numerous members of the HELP Committee signed
oversight letters requesting the information from the Food and
Drug Administration, the Massachusetts Board of Pharmacy, and
the New England Compounding Center.
The HELP Committee worked very effectively and in a
bipartisan manner to reauthorize the FDA user fee legislation
earlier this year. I am confident we can all work together to
arrive at a common understanding of this problem and its
solution.
I'm also interested in hearing from Dr. Kasey Thompson of
the American Society of Health-System Pharmacists on our third
panel. Many patient populations and specialties require
compounded products, including pediatrics and hospice. Some
State pharmacy boards, like Wyoming's, also do their jobs
effectively. I hope he can comment on the benefits of
traditional pharmacy compounding and the strengths and
weaknesses of pharmacy regulation by the States.
Last, I want to thank Dr. Bell from the CDC and Dr. Kainer
for attending today. Without your hard work, I understand this
could have been much worse. Patients all over the country owe
you thanks for immediately acting upon hearing about only one
case.
Thank you, Chairman Harkin, for holding this important
hearing, and I look forward to learning more about how this
tragedy occurred in order to see that it's not repeated in the
future.
The Chairman. Thank you very much, Senator Enzi.
It has been a longstanding procedure of this committee that
only the chair and the ranking member give opening statements.
The chair, with the concurrence of the ranking member, would
diverge from that for this hearing because of the long-time
interest in and leadership by Senator Roberts on this issue and
because he had been a leader on a bill that came up about 5 or
6 years ago. I would yield for no more than 5 minutes for an
opening statement by Senator Roberts.
Statement of Senator Roberts
Senator Roberts. Thank you, Mr. Chairman, and Ranking
Member Enzi. The reason I'm making this statement is very
simple. I've been involved in this for 12 years. This is not a
new story. I just appreciate you allowing me to make a short
statement. I believe it's important to outline some of the
previous actions that members of this committee and the Senate
have taken in the past to review and take action on issues
relating to compounding pharmacy.
I want to begin by thanking the Chairman and the Ranking
Member for holding this hearing on a crisis that has gained
significance and deserves attention over the past few weeks but
is also an issue that many of us on the committee have worked
on for many years and for some over a decade.
First and foremost, I want to start out by reiterating my
support for pharmacy compounding. I know that compounding
serves a very important role for patients, such as patients who
are allergic to certain ingredients found in approved drugs or
for children who need a pediatric dosage of a drug.
Legitimate pharmacy compounding occurs when a patient has a
special medical need that cannot be met by an FDA-approved
drug. Their physician writes a specific prescription for the
patient, and then the individual pharmacist makes the
medication for the individual patient. This type of compounding
should continue. I want to work to ensure that we don't do
anything to alter that practice.
However, and unfortunately, the more traditional pharmacy
compounding is not why we are here today. We are here today
because there have been bad actors who are using the good name
of pharmacy compounding to mass produce products not approved
by the FDA and provide them to patients. Compounding products
are made for the individual patient and are, therefore, not
FDA-approved.
However, under the guise of traditional compounding, some
manufacturers have been mass producing and providing products
without the knowledge of the patient or their doctor.
Regrettably, this is not a new issue. There have been many
examples of injuries and deaths from unsafe compounded drugs
that stretch across the country. In fact, it goes back over a
decade or more. Throughout that time, I've had the privilege of
working with many members on this committee, more especially
Senator Burr, on issues relating to pharmacy compounding.
This is an issue that hit far too close to home in Kansas.
Several years ago, a pharmacist in Kansas City was found to be
diluting cancer drugs for his patients. Unfortunately, over
4,000 patients were affected before authorities could stop him.
Senator Kit Bond and I worked together at that time to hold the
first HELP Committee hearing on pharmacy compounding. We
requested a GAO report on the status of pharmacy compounding to
try to get some answers.
We sponsored what I always thought was a very simple
amendment to the Medicare Modernization Act to have the FDA
establish a committee to look into pharmacy compounding and
make any recommendations to improve and protect patient safety.
This committee was to terminate after 1 year. It was an
amendment supported in the Senate. Unfortunately, it was
stripped during the conference because some folks incorrectly
thought that the States were adequately regulating such
pharmacies and that additional Federal regulation would be an
undue burden.
I must say I think every member here on this committee time
and again has fought against additional Federal regulation and
placing undue burdens on any constituent, including my local
community pharmacists. I was amazed. Fast forward a few years
later. With Chairman Kennedy and Senator Burr, we once again
tried to take a closer look at the regulation and enforcement
of pharmacy compounding. In an effort to be open and
transparent, we produced a discussion draft along with Ranking
Member Enzi and Senator Reed and requested comments and
feedback.
While I don't think that discussion draft is anything that
I would recommend signing into law today, the intent was to
garner stakeholder feedback and apply it to our policymaking.
Instead, rather than working with us, we were faced with a full
grassroots effort to stop the discussion draft from moving
forward. I said then, and I would repeat now, that my intent,
and I believe the intent of others, was never to do away with
pharmacy compounding. What we needed were answers. What we got
was pushback.
Now, while it was ultimately Chairman Kennedy's decision
not to move forward with the discussion draft, I had hoped then
and continue to believe it is important today to revisit the
regulation, oversight, and enforcement of pharmacy compounding
at the Federal and State levels. There are obviously very
serious patient safety concerns. I have my own opinions on
where the cracks may be and ways to address these safety
concerns. To that end, I am working with my colleagues on the
HELP Committee to discover the appropriate measures we need to
put in place to protect patient safety.
Let me be clear. I have not and will not introduce any sort
of legislation to ban pharmacy compounding. However, the recent
and repeated loss of life has reiterated the need for
appropriate measures to be put in place to ensure that bad
actors can no longer take advantage of patients. Patients have
a right to know when they are receiving a product that is not
FDA-approved and the risk that may come with using it. As I
said during the last hearing we had on this subject, I fully
recognize the benefits of compounding pharmacy and that they
fill an important niche in the healthcare delivery system.
However, many questions need to be answered. How do we
define manufacturing versus compounding? What are we doing at
the State level to enforce regulations currently on the books?
How can we get States that do not have adequate regulations on
the books to improve? Are those who are inspecting properly
trained? Should we have a means to test products once they have
been compounded to ensure they are safe and accurate doses? Are
schools of pharmacy properly training individuals to compound
and what steps they should take to make sure they do so safely?
Why is there not a system of adverse event reporting?
These questions were important a decade ago and,
unfortunately, they continue to remain relevant today. My
expectation from today's hearing is to answer some of these
questions, learn more about the current state of regulation of
pharmacy compounding, and I anticipate that all of our
witnesses will commit to working fully with this committee to
address any potential gaps in the regulatory structure that
would potentially affect patient safety.
I thank the chair and my colleagues for their indulgence.
The Chairman. Thank you very much, Senator Roberts.
Now we'll turn to our first panel. We'll hear from Dr. Beth
Bell of the Centers for Disease Control and Prevention about
the public health impact of this outbreak and the CDC's role in
responding to it. Second, we'll turn to Dr. Peggy Hamburg,
Commissioner of the FDA, and then Dr. Lauren Smith of the
Massachusetts Department of Public Health to tell us about the
role of their agencies in regulating compounding pharmacies in
general and in investigating NECC, specifically. We'll ask them
about their views on what we can do to prevent future crises.
With that, all your statements will be made a part of the
record in their entirety. I'd ask that you limit your opening
statements to 5 to 7 minutes, and then we'll open it for
questions. Welcome, all of you. Thank you for being here.
Dr. Bell, we'll start with you. Please proceed.
STATEMENT OF BETH BELL, M.D., MPH, DIRECTOR, NATIONAL CENTER
FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES, CENTERS FOR
DISEASE CONTROL AND PREVENTION, ATLANTA, GA
Dr. Bell. Chairman Harkin, Ranking Member Enzi, members of
the committee, thank you for the opportunity to speak to you
today about CDC's response and ongoing activities in the
multistate outbreak of fungal meningitis and other infections.
CDC disease detectives work 24/7 to save lives and protect
Americans from harm. The fungal meningitis outbreak is a
reminder of the importance of CDC's ability to rapidly respond
to, to characterize, and to stop outbreaks of unexplained
illness and death.
My remarks today will focus specifically on the public
health response to the outbreak associated with injections of
contaminated preservative-free methylprednisolone acetate
produced by the New England Compounding Center, NECC. To begin,
I want to give particular credit to Dr. April Pettit, an
infectious disease doctor at Vanderbilt University, who
identified the first meningitis case and notified the State
health department. If Dr. Pettit had not acted, it is likely
that many more patients would have been exposed.
We are also fortunate that Dr. Pettit reached out to Dr.
Marion Kainer of the Tennessee Department of Health, who
quickly identified similar cases, reached out to CDC for
support, and identified the common exposures: three lots of
methylprednisolone acetate produced by NECC. Dr. Kainer's quick
response resulted in a voluntary national recall of the
suspected NECC lots within days of the first case being
reported. CDC then reached out to other State health
departments to marshal an enormous nationwide effort, including
rapidly contacting approximately 14,000 patients at risk.
The efforts of Dr. Kainer and the hundreds of other State
public health officials who responded to this outbreak did not
happen by chance. Despite trying economic times, we have worked
hard to build and sustain a network of trained public health
professionals that can rapidly detect and respond to outbreaks.
As State budget cuts have forced public health personnel
losses, we are fortunate to have been able to make a real
difference with CDC's direct financial and in-kind support.
Many of the outbreak responders are directly supported
through CDC's Epidemiology and Laboratory Capacity Cooperative
Agreement. Dr. Kainer is a graduate of CDC's Epidemic
Intelligence Service Training Program, and Tennessee is one of
CDC's 10 emerging infections program sites that receive
additional resources which supported their response in this
outbreak. The resources available through the Prevention and
Public Health Fund authored by this committee also made a
tangible difference in detecting and responding to the
outbreak.
I would also like to share information about some of the
patients affected by the outbreak and what CDC has done to try
to help them. As of November 14, a total of 461 cases,
including 32 deaths, have been reported in 19 States. The
approximately 14,000 people across the country who received the
contaminated medication include people like Diana Reed and
George and Lillian Cary.
Diana Reed of Brentwood, TN, was the primary caretaker of
her wheelchair-bound husband, Wayne, who suffers from Lou
Gehrig's Disease. Diana was healthy and physically active, but
after a neck injury, she turned to steroid injections to help
with her pain. Tragically, Diana received a contaminated
injection and became the third Tennessean to die of fungal
meningitis.
George Cary of Howell, MI, is husband of Lillian. Both
received contaminated steroid injections in September. Lillian
was the first to show symptoms and, tragically, lost her battle
to fungal meningitis. While grieving the loss of his wife,
George was also diagnosed with fungal meningitis himself and is
in the process of undergoing the long and difficult treatment.
These are just a few of the personal stories associated with
this tragic event.
Because this infection is so rare and few doctors have ever
treated it, CDC stepped in to ensure that patients were getting
the best possible care. We convened a panel of the Nation's
leading clinical fungal disease experts to work with CDC
scientists to help develop diagnostic and treatment guidance.
Even with treatment, we are seeing many patients return with
new symptoms and new conditions. We also fear that more exposed
patients will become ill before the outbreak is over.
Our focus going forward should be on preventing these
outbreaks in the future and ensuring that all products,
materials, and procedures used in healthcare are safe. We are
fortunate in this case for the clinical and public health
heroes like Drs. Pettit and Kainer in Tennessee.
I will end by again noting the thousands of patients and
families who have been directly affected by this event. Diana,
George, Lillian, and countless others put their faith in our
healthcare system. Patients deserve to be safe whenever they
receive their medical care.
Thank you.
[The prepared statement of Dr. Bell follows:]
Prepared Statement of Beth Bell, M.D., MPH
Chairman Harkin, Ranking Member Enzi, members of the committee,
thank you for the opportunity to speak to you today about CDC's
response and ongoing activities related to the multistate outbreak of
fungal meningitis and other infections. CDC works 24-7 to save lives
and protect people from harm and this outbreak illustrates the power of
public health in action both to identify serious health problems and to
coordinate a targeted response that protects our Nation and its
citizens from infectious disease threats.
I want to extend my sympathies to the patients affected by this
outbreak. Our hearts go out to the patients and families impacted by
the debilitation and death from these infections.
My remarks today will focus specifically on the identification of,
and subsequent public health response to the outbreak associated with
injections of contaminated preservative-free methylprednisolone acetate
(MPA), an injectable steroid produced by the New England Compounding
Center (NECC). Specifically, I will cover three critical areas related
to the outbreak:
a summary of the response by CDC and our partners in State
public health agencies;
a description of the fungal infections involved in this
outbreak and how these infections are affecting patients; and
a discussion of several early lessons learned.
As of November 14 at noon (EST), a total of 461 cases, including 32
deaths, have been reported in 19 States. The cases include fungal
meningitis, stroke, or other central nervous system-related infections
plus 10 peripheral joint infections (i.e., knee, hip, shoulder, elbow).
CDC and our partners at State and local health departments marshaled an
enormous effort nationwide to determine the source and scope of the
outbreak, rapidly contact patients at risk, and enlist the individual
input of leading experts to help us develop novel diagnostic and
treatment guidance to achieve the best possible patient outcomes. In
this outbreak, local infectious disease officials, including State
epidemiologists, healthcare associated infection (HAI) prevention
coordinators, and others whose positions are directly supported through
CDC's Epidemiology and Laboratory Capacity (ELC) cooperative agreement
and CDC's Emerging Infections Program (EIP) were pivotal in the
original identification of the outbreak and the substantial patient
notification that followed. Their efforts at the State and local level
have been extraordinary and in many cases undoubtedly contributed
directly to saving the lives of exposed patients.
I would like to highlight some specific efforts by CDC and State
health agencies:
The Tennessee Department of Health (TN DOH) identified and
sounded the alarm on the initial cluster of cases. The TN DOH official
who alerted others about these cases serves as the State's HAI Program
Director and is a graduate of CDC's Epidemic Intelligence Service (EIS)
program. Tennessee also is one of CDC's 10 Emerging Infections Program
(EIP) sites and as such receives additional resources that helped
support their response in this outbreak.
The Virginia Department of Health laboratory, whose staff
had been trained by CDC in identifying fungi, was the first to identify
the very rare fungal pathogen, Exserohilum. This discovery saved
valuable time and provided the Nation with a critical piece of
information to guide diagnostic and treatment recommendations.
The Michigan Department of Community Health identified the
first case of a joint infection associated with these products.
Over 250 Federal disease control specialists have been
working out of CDC's Emergency Operations Center to coordinate the
multistate fungal outbreak response efforts with Federal, State, local,
tribal, and territorial public health partners. CDC coordination was
helpful to ensure patient notification, development and dissemination
of treatment guidance, and rapid communication to the public and the
health professions community.
State and local public health departments, health
care facilities, and CDC tracked down and contacted over 14,000
exposed patients in 23 States with facilities which received
the implicated medication.
CDC engaged the Nation's leading clinical fungal
disease experts to receive their individual input on the
development of diagnostic and treatment guidance appropriate
for identifying and treating patients that develop infections.
This panel has met repeatedly as the outbreak has evolved to
adjust clinical advice to very complex and rare infections. CDC
has educated over 4,200 clinicians through our clinician
conference calls (COCA calls) on the interim diagnostic and
treatment guidance.
CDC has prioritized transparent and rapid
communication with the public in this outbreak. To date, CDC's
meningitis outbreak and fungal diseases web pages have been
accessed over 1 million times and have sourced media outlets
with direct links and resources to ensure accurate reporting
and broad dissemination of health messages. CDC has used the
Health Alert Network (HAN) to release multiple health
advisories as the outbreak has unfolded. HANs are directly
distributed to health care providers nationwide. CDC has also
responded to over 4,500 calls to our public inquiry line (CDC-
INFO).
CDC's mutually reinforcing laboratory and surveillance
systems have been critical in confirming the cause of the outbreak:
CDC's fungus laboratory is the national reference
laboratory and in this outbreak has served as an indispensable
resource to public health and FDA laboratories to identify and
confirm the variety of fungal species recovered from patient,
product, and environmental samples. Because there were no
available rapid diagnostic tests to identify the fungal
organism(s) associated with this outbreak, CDC scientists
developed and refined a real-time polymerase chain reaction
(PCR) to detect fungal ribosomal DNA, and then performed DNA
sequencing to identify the specific fungus by its DNA barcode.
CDC's HAI laboratory is working with FDA to identify
other microorganisms from sealed medication vials. Few
laboratories nationwide have the technical expertise and
capacity to perform such complicated and exact testing to
assess the presence of any bacterial contamination.
CDC's Infectious Diseases Pathology laboratory has
been testing biopsy and autopsy samples from the outbreak.
Information from these analyses provides vital clinical
information on how this rare disease is affecting patients, and
such information is used to inform development of CDC's interim
clinical guidance.
evolution of the outbreak
On September 18, an astute clinician alerts the Tennessee
Department of Health (TN DOH) of a patient with culture-confirmed
Aspergillus fumigatus meningitis after epidural steroid injection at an
ambulatory surgical center (ASC).\1\ The patient received an epidural
steroid injection on July 30 and was admitted to the hospital in late
August.
---------------------------------------------------------------------------
\1\ www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm?s_cid=mm61e1012a1_w.
---------------------------------------------------------------------------
This type of infection is exceedingly rare, and we are extremely
fortunate that the clinician chose to test the patient's cerebrospinal
fluid (CSF) for a possible fungal infection (which is not a routine
test ordered by clinicians) and then notify the State health department
when those results came back positive. After further consultation with
the clinician in Tennessee, the TN DOH contacts CDC on September 20 to
ask if CDC has received similar reports of unexplained fungal
meningitis infections. CDC relays that it had not received reports of
unexplained fungal meningitis infections and recommends that the TN DOH
conduct a site visit to the ambulatory surgical center where the
epidural injection was administered.
On Friday, September 21, the TN DOH follows up with CDC about the
results of the site visit. TN DOH relays that multiple products and
exposures could be the source of the infection, including epidural
injection tray kits, preservative-free contrast media, povidone-iodine,
lidocaine, and preservative-free MPA from NECC.\2\ External
contamination of supplies in a common storage area at the ASC was also
considered as a possible source of infection. CDC recommends that TN
DOH continue to gather detailed information, including lot numbers on
all of the products and sources of exposure, to facilitate further
investigation. Over the weekend, the TN DOH works with the ASC and area
hospitals to gather additional information and checks if there are any
other Aspergillus or unexplained meningitis cases.
---------------------------------------------------------------------------
\2\ Kainer, M., et al. Outbreak of Neuroinvasive Fungal Infections
Associated with Epidural Steroid Injections, Tennessee, 2012.
---------------------------------------------------------------------------
On Monday, September 24, CDC and TN DOH discuss the investigation.
The discussion focuses on additional patients with meningitis from the
same ASC with similar procedures and product exposures uncovered by the
TN DOH over the weekend. CSF cultures from the additional patients with
meningitis were negative, but all presented with a clinical picture
similar to the index patient. CDC and TN DOH coordinate on next steps
of the investigation. The TN DOH contacts the Massachusetts Department
of Public Health (MA DPH) in an effort to obtain more information about
NECC and its products. TN DOH notifies MA DPH about its cluster of
meningitis cases following epidural steroid injections \3\ and that use
of MPA distributed by NECC is one of the common exposures under
investigation.
---------------------------------------------------------------------------
\3\ Kainer, M., et al. Outbreak of Neuroinvasive Fungal Infections
Associated with Epidural Steroid Injections, Tennessee, 2012.
---------------------------------------------------------------------------
On Tuesday, September 25, CDC notifies FDA that CDC and the TN DOH
are investigating a cluster of meningitis cases in a single ASC in
Tennessee that may be related to product contamination. CDC notes that
they are investigating several product exposures as possible sources of
infection. Also on Tuesday, the MA DPH and the MA Board of Pharmacy
organize a call with NECC, the TN DOH, and CDC to inform NECC of the
ongoing investigation and inquire about product information and adverse
event reporting. Public health authorities learn about how the MPA
steroid is prepared, request distribution lists for the three lots \4\
identified by the TN DOH and inquire about any reports of illnesses
related to MPA.\5\ NECC states that it has not received reports of
illnesses and that sterility testing, as well as environmental
monitoring, has not demonstrated any concerning results. The MA Board
of Pharmacy asks if NECC has a voluntary recall process in place if the
investigation confirms contamination. NECC affirms that it does have a
voluntary recall process in place.
---------------------------------------------------------------------------
\4\ Lot #05212012@68, BUD 11/17/2012; Lot #06292012@26, BUD 12/26/
2012; Lot #08102012
@51, BUD 2/6/2013.
\5\ www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm's_cid=mm61e1012a1_w.
---------------------------------------------------------------------------
The following day (September 26), the MA Board of Pharmacy
initiates an inspection of NECC \6\ and NECC issues a voluntary recall
of the three lots of MPA identified by the TN DOH. Approximately 3,000
doses of MPA are quarantined or returned.\7\ CDC is provided an invoice
list of all facilities that received possibly contaminated lots and
begins work with TN DOH and other State health departments to contact
other clinics from the NECC distribution list to see if they are aware
of any meningitis cases of unknown etiology. CDC also provides an
update to FDA about the NECC call and informs FDA that NECC initiated a
voluntary recall of the three lots of MPA though there was no specific
evidence of product contamination. CDC asks FDA to query MedWatch
reports for any related cases; the MedWatch query ultimately identifies
the previously known cases from the Tennessee ASC. During this time,
CDC continues to pursue other possible sources of the outbreak and
contacts the New York Department of Health for assistance in contacting
the company that produced the epidural injection trays used at the
Tennessee ASC.
---------------------------------------------------------------------------
\6\ MA DPH NECC Preliminary Investigation Findings: ``. . .
investigators found NECC employees cleaning sterile compounding areas
and conducting environmental testing. MA DPH investigators also
detected signs of bleach decontamination in the compounding areas.''
\7\ MA DPH NECC Preliminary Investigation Findings.
---------------------------------------------------------------------------
On September 27, FDA and MA DPH begin coordination for a
collaborative investigation of NECC.\8\ A case is identified in another
State \9\ as North Carolina reports its first patient with meningitis
of unknown etiology following epidural spinal injection to CDC late
that evening. This is significant because it is the first evidence that
the exposure may not be isolated to the TN ASC. CDC begins working with
the TN DOH and NC DOH to identify common exposures in new cases from
both States which include MPA from NECC as well as the same brands of
povidone iodine and lidocaine. Of the patients identified thus far,
only one has a culture-confirmed Aspergillus fungal meningitis
infection. The additional patients have a similar clinical presentation
of meningitis as the index case with Aspergillus, but no
microbiological data yet link them together. The microbiological key
comes later in the outbreak when the Virginia Department of Health (VA
DOH) in consultation with CDC's infectious disease pathology laboratory
links an unexplained death to the outbreak and identifies Exserohilium
as the fungal pathogen related to that case.
---------------------------------------------------------------------------
\8\ MA DPH NECC Preliminary Investigation Findings.
\9\ http://www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm?s_cid=mm61e1012a1
_w.
---------------------------------------------------------------------------
On Friday, September 28, CDC requests all 23 States with clinics
that received the three MPA lots from NECC begin contacting patients
who received epidural injections to see if there are any other
meningitis cases of unknown etiology. Through the weekend of September
29-September 30, CDC posts outbreak information to ClinMicroNet (a
network of clinical labs) and the Emerging Infections Network (EIN, a
network of infectious disease physicians) to help identify any
additional Aspergillus meningitis cases or meningitis cases of unknown
etiology.
On Monday, October 1, FDA and MA Board of Pharmacy initiate a joint
inspection of NECC.\10\ Investigators find violations of MA pharmacy
regulations \11\ and the MA DPH issues a formal quarantine notice.\12\
---------------------------------------------------------------------------
\10\ http://www.cdc.gov/media/releases/2012/
t1004_meningitis_outbreak.html.
\11\ MA DPH NECC Preliminary Investigation Findings--Investigators
found that methyl-
prednisolone products labeled as patient specific were not individual
prescriptions but lists of patients generated by a clinic and provided
to NECC to obtain the product which is a violation of MA pharmacy
regulations.
\12\ MA DPH NECC Preliminary Investigation Findings--``The Notice
directed that all methylprednisolone acetate raw materials (chemicals),
all non-sterile products located at NECC used in the compounding of
methylprednisolone acetate, and all inventory on the premises prepared
for dispensing and stored at the pharmacy, or received by recall should
be quarantined and not disposed of without the express approval of the
DPH.''
---------------------------------------------------------------------------
The following day, CDC initiates a call with the 23 States that
received the three NECC lots of MPA to provide updates on the
investigation and share information on meningitis cases of unknown
etiology as well as common exposures. While NECC products are
considered the likely source of the outbreak, the investigation does
not find conclusive evidence of NECC product contamination until
October 4 when FDA announces it has identified by microscopy visible
fungal contamination of previously sealed vials of MPA from NECC from
one of the three lots identified by TN DOH.
With conclusive identification of fungal contamination, CDC
activates its Emergency Operations Center on October 4 and intensifies
outreach to patients and clinicians to ensure appropriate patient
diagnosis and treatment. CDC also launches a fungal meningitis outbreak
Web site to provide continual updates to patients, clinicians, and the
public, and by October 5, CDC posts the lists of the clinics that had
received the three implicated lots of MPA to facilitate patient
followup. Additionally, CDC and FDA laboratories work on pathogen
identification in patient, product, and environmental samples. This
combined laboratory effort ultimately recovers multiple bacterial and
fungal contaminants from sealed NECC products labeled as sterile.
the patient experience with fungal meningitis and related infections
We do not yet have a full picture of the extent of the impact of
this tragic outbreak, which clearly has devastating impacts on patients
and their families. Contaminated medication was administered by
injection to thousands of people, resulting in an outbreak of fungal
meningitis and other infections. Exserohilum rostratum, the predominant
fungal species in this outbreak, is a common brown-black mold found in
soil and on plants, especially grasses, that thrives in warm and humid
climates. Fungal infection caused by Exserohilum rostratum is rare and
when it does occur it has generally been documented as a cause of sinus
and skin infections. Diagnosis of fungal meningitis, particularly with
molds, is extremely difficult because traditional diagnostic methods
such as culture have limited yield.
The clinical syndromes of these infections are rare and thus lack
clinical trials or other experience that provide evidence for optimal
treatment. Available treatments are not straight-forward because of
potential adverse events and variability among patients. With little
literature describing these types of infections and limited clinical
experience available, CDC solicited the individual input of outside
mycology experts to help develop novel diagnostic and treatment
guidance for patients at risk for these fungal infections. CDC has
worked with these experts throughout the outbreak to update our interim
guidance as more information has become available about the clinical
experience of patients. Adequate duration of antifungal treatment is
unknown although we expect a minimum of 3 months' treatment be
considered. CDC has sent staff to States and worked with State and
local health departments to abstract medical charts and gather
information on patients' ongoing clinical experiences. CDC has
disseminated our treatment guidance through web postings, blast e-mails
to professional societies, and multiple clinician-specific conference
calls.
As of November 13, the median age of the patients is 65 years
(range: 16-92 years) and over 60 percent are female. While most of the
cases have presented with meningitis, we have also seen cases of
stroke, epidural abscess (infection between the outer covering of the
brain and spinal cord and the bones of the skull or spine),
osteomyelitis (bone infection), and septic arthritis (joint infection).
Many patients with meningitis had only a few mild symptoms, such as
headache and/or nausea or vomiting.
The incubation period has ranged from 0 to 120 days with a median
of 20 days. Based on current data, the highest risk is likely to be in
the first 42 days (6 weeks) after last injection. Maximum incubation
period for infection is not known, and the incubation period could be
longer for some patients. Thus, asymptomatic but exposed patients
should remain vigilant for symptoms and seek medical attention should
symptoms develop. The clinical situation is still evolving. Even with
treatment, we are seeing many patients return after being discharged
from the hospital with new symptoms and other conditions such as
arachnoiditis (inflammation of the membranes that surround nerves) and
abscesses at the original injection sites. This suggests that there may
be long-term complications for patients that have not yet become
apparent.
To support ongoing clinical efforts, CDC has developed a Clinicians
Consultation group consisting of a network of leading clinical
infectious disease and fungal disease experts nationwide who have
volunteered to provide consultation with clinicians providing direct
patient care. CDC is also planning to continue to follow cases to help
track the course of treatment and provide ongoing information on
patient outcomes.
early lessons learned
Outbreak responses require skilled, trained public health personnel
in State and local agencies. In this outbreak, we were fortunate that
trained individuals were already ``on the ground'' in key positions,
reinforced by already-established surveillance and laboratory capacity.
Personnel cuts at the State and local levels have made CDC support to
State infectious disease programs key to these efforts. CDC's
Epidemiology and Laboratory Capacity (ELC) cooperative agreement and
the Emerging Infections Program (EIP) support this critical infectious
disease capacity and networking.
This outbreak is also a reminder of the importance of CDC's
infectious disease epidemiologists and laboratories to rapidly respond
to and characterize outbreaks of unexplained death and illness. This
outbreak exemplifies the work of CDC's disease detectives to track down
and solve public health problems. CDC's laboratory capacity for
infectious diseases has been a critical element in the response,
identifying rare or obscure pathogens and providing added capacity as a
backstop to States. With declining local resources, many States have
cut back on maintaining fungal testing and instead rely upon CDC's
fungus laboratory. During the peak of laboratory testing, CDC's fungus
laboratory was operating 7 days a week to test the hundreds of
outbreak-related samples. This outbreak has also underscored the
importance of bioinformatics and genomics technologies that can help
CDC and States more rapidly and decisively detect, respond to, and
control large outbreaks like this one.
CDC plays a vital role not only in responding to these outbreaks
but in preventing them as well. For years, CDC and its State public
health partners have been the first-responders to multiple outbreaks
stemming from suboptimal practices in handling sterile medications in
clinics and in pharmacies. We are learning that many of these outbreaks
are the result of a widespread lack of knowledge of or adherence to
well-recognized regulatory and professional standards for properly
handling sterile medications.
concluding remarks
This outbreak demonstrates the essential role that public health
plays in identifying and responding to infectious disease outbreaks
large or small. Our national public health capacity is disseminated to
State and local responders who work on a daily basis to keep our
country safe from infectious diseases--whether they are from naturally
emerging threats such as a new influenza pandemic or from human-made
problems such as contaminated medicines. CDC will continue to work with
State partners, national experts, front-line clinicians and others to
respond to the critical public health needs related to this outbreak.
The Chairman. Thank you very much, Dr. Bell.
Now we'll turn to Dr. Peggy Hamburg, the Commissioner of
the Food and Drug Administration. Dr. Hamburg and Dr. Smith, I
know you were both at the House hearing yesterday. I hate to
have you do double duty, but that's the way this system works.
We wanted you over here also to be able to speak with us, so we
could also engage you in questions about the role of both the
FDA and the Massachusetts inspections.
Dr. Hamburg, please proceed.
STATEMENT OF MARGARET A. HAMBURG, M.D., COMMISSIONER, FOOD AND
DRUG ADMINISTRATION, WASHINGTON, DC
Dr. Hamburg. Thank you very much, Mr. Chairman and members
of the committee. I appreciate the opportunity to testify about
this tragic fungal meningitis outbreak associated with an
injectable steroid product distributed by NECC as well as to
focus on the safety concerns related to compounding and
legislation that is needed to prevent such incidents from
happening again.
I want to, of course, begin by offering my sympathies to
the patients affected by this outbreak and their families. This
event has had devastating effects on patients across the
country, many of whom were likely unaware that they were
receiving a drug that was compounded, not reviewed or approved
by the FDA.
Our foremost goal is the protection of the public health.
Since the onset of this outbreak, we've targeted FDA resources,
from experts in our headquarters to inspectors and scientists
in district offices and labs across the country, to do
everything we can to stem the toll of this terrible event.
Together, with CDC and the States, we've sought to identify
potentially contaminated products and ensure that they are
removed from market and don't reach patients. We've collected
and analyzed hundreds of samples from the relevant firms, as
well as from medical facilities and State and local agencies,
to isolate the cause and determine the extent of the
contamination. We're working daily to ensure that timely,
clear, and accurate information is disseminated about the
findings of our investigation, what products are affected, and
what providers should do with any product still on their
shelves. We're working to alleviate existing drug shortages
that could be exacerbated by product recalls.
We've also been reviewing actions taken in the past with
regard to NECC. In a tragedy of this magnitude, you always look
back to see what more could have been done. Certainly, we
should have sent the warning letter more swiftly and done the
inspection originally planned. From our review thus far, we
have no reason to believe that any of those specific actions in
question, more timely issuance of the 2006 warning letter or
inspectional follow-up, would have prevented this recent
tragedy.
What we do know is that stronger, clearer authority would
enable more effective regulation of the drug compounding
industry, especially when it's been evolving so significantly.
As it is, our authority over compounding is limited, unclear,
and contested. In the face of differing views in Congress and
the courts about FDA's authority and continuing challenges by
industry, the agency has struggled with how to chart an
effective course to protect the public health.
Like Senator Roberts, we recognize that traditional
compounding provides an important service for patients who, for
example, can't swallow a pill or are allergic to an ingredient
in a drug product. The industry has evolved well beyond a
neighborhood pharmacist. In particular, the movement by many
hospitals to outsource pharmacy compounding has created a
market for compounding operations that produce drugs that reach
far larger numbers of patients.
When these facilities operate well, they may serve an
important function in terms of safety and efficiency. However,
when they fail to follow safety and quality standards, many
patients may be harmed. Our best information is that there are
thousands of other compounders out there producing what should
be sterile products made to exacting standards, and thus many
other firms with the potential to generate a tragedy like this.
The current oversight framework, in attempting to draw a
bright line between compounders and manufacturers, fails to
address the complex issues raised by the changing nature of the
industry. Additionally, gaps and ambiguities in the law have
hampered our ability to act to protect patients and to prevent
rather than to react to safety problems.
I am committed to working with Congress and other
stakeholders to design a system of rational, risk-based
regulation that takes into account both the Federal and State
rules. As I outlined in my testimony, we have developed a
proposed framework that would tier the degree of oversight to
the risk posed by the type of product and practices.
Traditional compounding would remain the purview of the States.
The higher risk posed by nontraditional compounding would
be addressed by Federal standards, including standards for
quality control. Under this framework, certain products
carrying the highest risk could not be compounded. They could
only be produced by entities willing to meet the standards
currently required of drug manufacturers.
We would also like to explore with you authorities that
would be important to support this new regulatory paradigm,
including clear authority to access records, mandatory
reporting of adverse events, additional registration
requirements to facilitate appropriate oversight and
coordination with State regulators, clear label statements to
allow prescribers and consumers the opportunity to make
informed judgments, and adequate funding to support the
inspections and oversight activities outlined in the framework.
Because a key piece of any plan involving oversight of
pharmacy compounders will continue to be performed at the State
level, we must work closely with our State partners as we
develop the framework for new authorities. FDA will be inviting
representatives from all 50 States to participate in a full-day
meeting on December 19 to facilitate these important
discussions and to strengthen our working relationship with the
States.
We have a collective opportunity and responsibility to help
prevent future tragedies. If we fail to act, this type of
incident will happen again. It is a matter of when, not if, I'm
afraid. If we fail to act now, it will only be a matter of time
until we're all back in this room asking why more people have
died and what could have been done to prevent it.
I am happy to answer any questions you have and look
forward to working with you on this very important public
health issue.
[The prepared statement of Dr. Hamburg follows:]
Prepared Statement of Margaret A. Hamburg, M.D.
introduction
Mr. Chairman and members of the committee, I am Dr. Margaret
Hamburg, Commissioner of Food and Drugs at the Food and Drug
Administration (FDA or the Agency), which is part of the Department of
Health and Human Services (HHS). Thank you for the opportunity to be
here today to discuss important issues related to the tragic fungal
meningitis outbreak associated with compounded methyl-
prednisolone acetate (MPA), a steroid injectable product distributed by
the New England Compounding Center (NECC), and to discuss more broadly
safety issues related to pharmacy compounding.
I want to begin by offering my deepest sympathies to the patients
affected by this outbreak and their families. This outbreak has had
devastating effects on individuals and families across the country. The
Centers for Disease Control and Prevention (CDC) has reported 32 deaths
among 438 individual cases (428 cases of fungal meningitis and 10 cases
of peripheral joint infections) \1\ across 19 States. Approximately
14,000 patients may have received injections with MPA from three
implicated lots. In addition, two other NECC products have been found
to be contaminated with different bacteria. We have found no adverse
health effects to date from these additional products, but continue to
investigate the public health implications of this contamination.
---------------------------------------------------------------------------
\1\ Four-hundred and twenty-eight cases of fungal meningitis,
stroke due to presumed fungal meningitis, or other central nervous
system-related infection meeting the outbreak case definition, plus 10
peripheral joint infections (e.g., knee, hip, shoulder, elbow).
---------------------------------------------------------------------------
Although the investigation is ongoing, we want to provide you with
an update on the actions that FDA has taken, and is continuing to
respond to this outbreak. We also want to suggest steps that Congress
can take to strengthen FDA's authority to help prevent tragedies like
this from happening in the future.
fda's response to the current outbreak
FDA's primary goal since the onset of this outbreak has been to
protect the public health. With the State and Federal partners, we are
conducting thorough investigations of the relevant facilities,
monitoring the voluntary recalls associated with these products to
ensure that contaminated and potentially contaminated product is off of
the shelves, and ensuring that information is communicated promptly and
clearly to health care professionals and patients.
Let me briefly summarize the sequence of key events regarding the
outbreak. On September 25, 2012, CDC notified FDA that it was working
with the Tennessee Department of Health to investigate a cluster of
meningitis cases at a single clinic, which might be associated with
product contamination. When we learned of the potential contamination,
we joined CDC in investigating. On September 26, NECC began a voluntary
recall of three implicated lots of MPA and voluntarily ceased
manufacturing of MPA. The Massachusetts Board of Registration in
Pharmacy, which has primary oversight responsibility for pharmacies in
its State, oversaw the recall, and initiated a 1-day inspection of
NECC's Framingham, MA, facility. FDA also began to coordinate with the
Massachusetts Board of Registration in Pharmacy to plan for inspection
of NECC. We coordinated closely with the State on this adverse event
inspection, because the State has authority to compel certain actions
where our authority is more limited.
FDA and the Massachusetts Board of Registration in Pharmacy
initiated a joint inspection of NECC on October 1, 2012. On October 4,
FDA and CDC held a joint press conference announcing the investigation
of the meningitis outbreak.\2\ On October 5, after FDA had observed
fungal contamination by direct microscopic examination of foreign
matter taken from a sealed vial of MPA collected from NECC, FDA issued
a MedWatch Safety Alert to 220,000 health professionals to notify them
of the fungal contamination. Out of an abundance of caution, the Safety
Alert took the additional step of recommending that health care
professionals and consumers not use any product produced by NECC. FDA
also requested that health care professionals retain and secure all
remaining products purchased from NECC until FDA provided further
instructions about how to dispose of these products. In addition, the
Safety Alert encouraged health care professionals and patients to
report to the Agency's MedWatch Safety Information and Adverse Event
Reporting Program any adverse events or side effects related to the use
of these products. On October 6, at FDA's recommendation, NECC agreed
to recall all products.
---------------------------------------------------------------------------
\2\ ``CDC and FDA Joint Telebriefing on Investigation of Meningitis
Outbreak'' (October 4, 2012); transcript available at http://
www.cdc.gov/media/releases/2012/t1004_meningitis_
outbreak.html.
---------------------------------------------------------------------------
As our investigation continued, on October 11, we announced our
findings showing the presence of a fungal contaminant in multiple
sealed vials of MPA injection, made at the NECC's Framingham, MA site.
CDC confirmed the specific type of fungus related to the patient
disease--Exserohilum--in this briefing as well.\3\ On October 15, based
on FDA's ongoing investigation and out of an abundance of caution, we
further advised health care professionals to followup with patients who
were administered any NECC injectable product on or after May 21, 2012,
including an ophthalmic drug that is injectable or used in conjunction
with eye surgery or a cardioplegic solution. After working closely with
the State on October 22, the Agency made available two lists of
customers (consignees) who received products that were shipped on or
after May 21, 2012, from NECC's Framingham, MA facility, advising those
customers to check their stocks to identify whether they had any
products from NECC, and if so, to immediately isolate any identified
product from their drug supplies and contact NECC to obtain
instructions on how to return products.
---------------------------------------------------------------------------
\3\ ``CDC, FDA, Massachusetts Department of Public Health: Joint
Telebriefing Updating Investigation of Meningitis Outbreak'' (Oct. 11,
2012); transcript available at http://www.cdc.gov/media/releases/2012/
t1011_meningitis_outbreak.html.
---------------------------------------------------------------------------
On October 26, FDA released a copy of the FDA Form 483 (list of
observations made during the on-site inspection) issued to NECC. FDA
observed, and has since confirmed, that contaminated products were made
at NECC's Framingham, MA facility, and listed a number of observations
made during the course of the inspection regarding conditions in the
clean room at this facility.
Most recently, on November 1, FDA and CDC laboratories announced
that bacteria had been identified as present in three separate lots
(batches) of NECC-supplied, preservative-free injectable betamethasone,
with each lot producing different culture results (identifying
different contaminants), and in a single lot of NECC cardioplegia
solution. FDA stated that although final laboratory results on
additional samples were still pending, the previous finding of fungal
contamination of MPA and recent finding of bacterial contamination of
injectable betamethasone and cardioplegia solution reinforced the
Agency's concern about the lack of sterility in products produced at
NECC's compounding facility and served to underscore that hospitals,
clinics, and health care professionals should not use any NECC-supplied
products.
The Agency has been working closely with CDC, numerous State health
departments, and the Massachusetts Board of Registration in Pharmacy to
investigate the outbreak of fungal meningitis. This is a far-ranging
investigation across the United States. FDA, in conjunction with our
State partners, is in the process of inspecting several facilities
associated with this outbreak. This includes compounders, wholesale
distributors, active pharmaceutical ingredient (API) suppliers,
contract laboratories, and others. The Agency's first priority has been
to detect any contaminated or potentially contaminated products, to
prevent them from reaching U.S. consumers by ensuring they are
effectively recalled and removed from the market, and, as discussed
more fully below, to communicate key information about these products
to the providers and patients who need it. In connection with this
investigation, FDA has collected and analyzed hundreds of samples from
firms associated with this outbreak, as well as from medical facilities
and State and local agencies. In addition to staff at FDA headquarters,
staff in FDA district offices in New England, New York, Dallas,
Seattle, Chicago, Los Angeles, Detroit, Cincinnati, Kansas City, and
Florida, and laboratory personnel in Denver, San Francisco, Atlanta,
New York, and Boston, are assisting in this investigation.
FDA also inspected Ameridose LLC's facility in Westborough, MA as
part of the Agency's ongoing fungal meningitis outbreak investigation.
Ameridose and NECC share some of the same management. Ameridose entered
into a voluntary agreement with the Massachusetts Board of Registration
in Pharmacy to temporarily cease all pharmacy and manufacturing
operations starting on October 10, 2012. After FDA's preliminary
inspectional findings raised concerns about a lack of sterility
assurance for products produced at and distributed by Ameridose's
Westborough facility, the company voluntarily recalled all of its
unexpired products in circulation. FDA completed its inspection on
November 9, 2012.
FDA is currently conducting recall audit checks of NECC's
customers. In an audit check, FDA contacts a subset of the firm's
customers, which in this case were health care facilities, to confirm
that they received notice of the recall and took the action requested
in the recall notice.
In this case, the facilities were instructed to immediately
segregate and quarantine the material and to work with NECC to
coordinate return of the products. As of November 5, 2012, FDA had
completed 587 audit checks of NECC's health care facility customers.
FDA found no product remaining for use at any of the NECC customers
that it audited, and all customers had knowledge of the recall.
Ameridose commenced its product recall on October 31, 2012; FDA
initiated its audit check process for the Ameridose recall on November
5, 2012.
FDA has identified six Ameridose products that were on the FDA drug
shortage list prior to the recall (sodium bicarbonate injection;
succinylcholine injection; atropine sulfate injection; bupivacaine
hydrochloride injection; lidocaine hydrochloride injection and
furosemide injection).
These six drugs were in shortage before the Ameridose shutdown due
to manufacturing problems, delays, and discontinuations by commercial
manufacturers. FDA's Drug Shortage Program is using every tool
available to work with manufacturers to address these shortages. For
five of the drugs, we expect the shortages to decrease based on all of
the ongoing efforts of FDA and the manufacturers to address these
shortages and do not anticipate the Ameridose shutdown to create
additional issues. For sodium bicarbonate injection, we are continuing
all efforts to address the shortage, including exploring temporary
importation to assist with supplies until demand is being met by the
U.S. manufacturers.
FDA has communicated throughout this investigation with the media,
Congress, State health officials, health care professionals, and the
public to keep them apprised of important findings and developments as
we move forward in our investigation. FDA's Web site is updated on a
frequent basis to provide broad access to any new public information.
This information is being further disseminated through the Agency's
electronic listserves and through Twitter and Facebook. Along with CDC,
FDA is providing health care professionals with information they need
on an ongoing basis, and as new information comes to light, to advise
and treat patients affected by this situation.
Targeted alerts have been sent to 150 health care professional
organizations, including the national specialty-specific societies that
work with spinal injections, such as the American Society of
Anesthesiologists, the American Academy of Physical Medicine and
Rehabilitation, and the North American Spine Society, and also to all
State medical, pharmacist, nursing, and physicians' assistant
societies, as well as all State boards of pharmacy. Regular phone
updates are provided to State health departments, in collaboration with
CDC, and written updates are also distributed to national pharmacy and
ophthalmology professional organizations. FDA also contacted patient
and health care professional groups and consumer groups and worked with
the American Hospital Association as part of our response.
FDA pharmacists are fielding calls from the public and we have
extended their hours of availability for the last several weeks to help
respond to the public's concerns. We also continue to respond to calls
and e-mails from health care professionals, hospitals and clinics, and
others with questions about the NECC and Ameridose recalls.
The far-ranging investigation is ongoing and FDA will continue to
update stakeholders as quickly as possible as information becomes
publicly available.
FDA's past activities with respect to NECC include: a 2002
inspection in response to adverse event reports (followed by a State
inspection and action under Massachusetts' authority) and a 2006
Warning Letter focused on lower risk issues associated with copying
approved drugs, marketing and packaging. Throughout this time, NECC has
repeatedly disputed FDA's jurisdiction over its facility.\4\ The
Massachusetts Board of Pharmacy re-inspected NECC in 2011 in response
to a letter from the firm indicating that NECC was ``updating its
facility and moving into adjacent space''; that inspection included a
tour of the facility, security review, licensing review, and inspection
of NECC's sterile and non-sterile processing areas.\5\ The
Massachusetts Board of Pharmacy inspection found the facility to be
``Satisfactory.'' \6\
---------------------------------------------------------------------------
\4\ Inspection Report for April 2002 inspection, at PP. 2, 3, 5;
Establishment Inspection Report for 2002/2003 inspection, at p. 11;
Inspection Memorandum for 2004 inspection, at p. 3; Warning Letter
Response, at PP. 3-4.
\5\ A copy of MABRP's May 24, 2011, Inspection Report for NECC is
available on MABRP's Web site at http://www.mass.gov/eohhs/docs/dph/
quality/boards/necc/03-new-england-compound
ing-pharmacy-incnew-england-compounding-center-inspection-report.pdf.
\6\ See MABRP's May 24, 2011 Inspection Report for NECC, id., at p.
10.
---------------------------------------------------------------------------
fda's legal authority over compounded drugs
FDA regards traditional pharmacy compounding as the combining or
altering of ingredients by a licensed pharmacist, in response to a
licensed practitioner's prescription for an individual patient, which
produces a medication tailored to that patient's special medical needs.
In its simplest form, traditional compounding may involve reformulating
a drug, for example, by removing a dye or preservative in response to a
patient allergy. Or it may involve making a suspension or suppository
dosage form for a child or elderly patient who has difficulty
swallowing a tablet. FDA believes that pharmacists engaging in
traditional compounding provide a valuable medical service that is an
important component of our health care system. However, by the early
1990s, some pharmacies had begun producing drugs beyond what had
historically been done within traditional compounding.
After receiving reports of adverse events associated with
compounded medications, FDA became concerned about the lack of a policy
statement on what constituted appropriate pharmacy compounding. In
March 1992, the Agency issued a Compliance Policy Guide (CPG), section
7132.16 (later renumbered as 460.200) to delineate FDA's enforcement
policy on pharmacy compounding. It described certain factors that the
Agency would consider in its regulatory approach to pharmacies that
were producing drugs.
The compounding industry objected to this approach and several
bills were introduced, some with significant support, to limit the
Agency's oversight of compounding.\7\ In May 1996, in a House Commerce
Committee hearing on FDA reform legislation, FDA Commissioner David
Kessler testified that the compounding provision being considered by
the committee was likely to encourage large-scale manufacturing under
the guise of pharmacy compounding, and could allow for potentially
dangerous compounding of sterile products, leading to serious safety
problems or death.\8\
---------------------------------------------------------------------------
\7\ H.R. 5256, Pharmacy Compounding Preservation Act of 1994,
introduced Oct. 7, 1994, 1 co-sponsor; H.R. 598, Pharmacy Compounding
Preservation Act of 1994, introduced Jan. 20, 1995, 141 co-sponsors;
H.R. 3199, Drug and Biological Products Reform Act of 1996, introduced
March 29, 1996, 205 co-sponsors; H.R. 1060, Pharmacy Compounding Act,
introduced March 13, 1997, 152 co-sponsors; H.R. 1411, Drug and
Biological Products Modernization Act of 1997, introduced April 23,
1997, 16 co-sponsors.
\8\ Statement by David A. Kessler, M.D., Commissioner of Food and
Drugs, Dept. of Health and Human Services, before the Subcommittee on
Health and Environment, Committee on Commerce, House of Representatives
(May 1, 1996).
---------------------------------------------------------------------------
In November 1997, S. 830, the Food and Drug Administration
Modernization Act of 1997 (FDAMA) was signed into law as Public Law
105-115.\9\ FDAMA added to the FD&C Act's Section 503A, which addresses
FDA's authority over compounded drugs.\10\ Section 503A exempts
compounded drugs from three critical provisions of the FDCA: the
premarket approval requirement for ``new drugs''; the requirement that
a drug be made in compliance with current good manufacturing practice
(cGMP); and the requirement that the drug bear adequate directions for
use, providing certain conditions are met. These conditions include,
among other things, that the compounding be performed by a licensed
pharmacist or physician, that there be a prescription for the
compounded product for an individual patient, and that the compounded
product be necessary for an identified patient. It allows FDA to
restrict the compounding of certain categories of drugs (after notice-
and-comment rulemaking), and limits the quantity of compounded drugs
that a pharmacy could ship out of State to 5 percent of the total
prescription orders, unless the State enters into a Memorandum of
Understanding with FDA that addresses the distribution of ``inordinate
amounts'' of compounded drugs out of the State, and the handling of
complaints about compounded products shipped out of the State. Section
503A also contains restrictions on the advertising or promotion of the
compounding of any particular drug, class of drug, or type of drug, and
on the solicitation of prescriptions for compounded drugs from
prescribers. These provisions were the subject of subsequent court
challenges, which have produced conflicting case law and amplified the
perceived gaps and ambiguity associated with FDA's authority over
compounding pharmacies. We look forward to working with Congress to
address these issues.
---------------------------------------------------------------------------
\9\ Public Law 105-115, FDAMA, 111 Stat. 2296 (Nov. 21, 1997),
available at http://www.gpo
.gov/fdsys/pkg/PLAW-105publ115/pdf/PLAW-105publ115.pdf.
\10\ Id.
---------------------------------------------------------------------------
Looking Ahead
FDA believes that there is a legitimate role for traditional
compounding to provide needed drugs to patients that, for example, need
a drug that is allergen free or have a medical need that cannot be met
with an approved FDA product. However, we have grown increasingly
concerned about certain compounding practices, and we have seen an
increasing number of incidents related to compounded drugs. The NECC/
meningitis situation is the latest, and most serious, incident. As
described above, FDA's ability to take action against compounding, that
exceeds the bounds of traditional pharmacy compounding and poses risks
to patients, has been hampered by gaps and ambiguities in the law,
which have led to legal challenges to FDA's authority to inspect
pharmacies and take appropriate enforcement actions.
The Administration is committed to working with Congress to address
the threat to public health from gaps in authorities for effective
oversight of certain compounding practices. To that end, FDA has
developed a framework that could serve as the basis for the development
of a risk-based program to protect the public health.
Risk-based Framework
Recognizing the history of compounding practice, FDA supports the
long-standing policy that all compounding should be performed in a
licensed pharmacy by a licensed pharmacist (or a licensed physician),
and that there must be a prescription or order for an individual
patient who has a documented medical need for the compounded drug.
Further, we recommend that the statute recognize two categories of
compounding: traditional and non-traditional. ``Traditional
compounding'' would include the combining, mixing, or altering of
ingredients to create a customized medication for an individual patient
with an individualized medical need for the compounded product, in
response to a valid patient-specific prescription or order from a
licensed practitioner documenting such medical need. Traditional
compounding plays an important role in the health system and should
remain the subject of State regulation of the practice of pharmacy.
``Non-traditional compounding'' would include certain types of
compounding for which there is a medical need, but that pose higher
risks based on one or more of the factors identified below. Non-
traditional compounding would be subject to Federal standards adequate
to ensure that the compounding could be performed without putting
patients at undue risk. For example, enforcement could be by the FDA or
by a State willing to effectively oversee the compounding activities,
as determined by FDA.
Factors that could place a product into the ``non-traditional
compounding'' category might include some statutorily specified
combination of: the type of product/activity (e.g., sterile
compounding); the amount of product being made; whether the production
is being done before the receipt of a prescription or order for a
particular patient (so-called ``anticipatory compounding''); whether
the compounded drug is being shipped interstate; or whether the drug is
being dispensed to someone other than the ultimate user when it leaves
the facility where it was produced.
Non-traditional compounding should, because of the higher risk
presented, be subject to a greater degree of oversight, with the
riskiest products subject to the highest level of controls, such as
appropriate current good manufacturing practice (``cGMP'') standards
established by FDA. In addition, FDA believes that with noted
exceptions, certain products are not appropriate for compounding under
any circumstances. These products would include: (1) what are
essentially copies of FDA-approved drugs, absent a shortage
justification based on the drug appearing on FDA's shortage list; and
(2) complex dosage forms such as extended release products; transdermal
patches; liposomal products; most biologics; and other products as
designated by FDA. Producing complex dosage forms would require an
approved application and compliance with cGMPs, along with other
requirements applicable to manufactured drug products. We would seek to
permit the Secretary to have sufficient flexibility in this area to
make these exceptions necessary to address issues of public health.
FDA would like to explore with Congress other authorities that
would be important to support this new regulatory paradigm. For
example, FDA should be given clear, full authority to collect and test
samples of compounded drugs and to examine and collect records in a
compounding pharmacy, just as the agency does when inspecting other
manufacturers. FDA should have clear statutory authority to examine
records such as records of prescriptions received, products shipped,
volume of operations, and operational records such as batch records,
product quality test results, and stability testing results. Such
inspections are necessary to determine when a pharmacy exceeds the
bounds of traditional compounding, to respond to public health threats,
and to enforce Federal standards.
FDA also believes that pharmacies engaged in non-traditional
compounding should register with FDA so that FDA can maintain an
accurate inventory of such pharmacies to facilitate appropriate
oversight and coordination with State regulators. In addition, FDA
would like to explore with Congress several other ideas such as clear
label statements identifying the nature and source of the non-
traditionally compounded product, and requiring non-traditional
compounders to report adverse events. The labeling statements would
provide prescribers and consumers with valuable information about the
products they are using or taking so that they can make informed
judgments about their use. Requiring non-traditional compounders to
report adverse events, as drug manufacturers are required to do, would
allow FDA and the States to identify trends and to proactively take
steps to curtail dangerous compounding practices. Other appropriate
regulatory and enforcement tools might also be useful. Funding will be
necessary to support the inspections and other oversight activities
outlined in this framework. We look forward to working with Congress to
explore the appropriate funding mechanisms to support this work, which
could include registration or other fees, as Congress has authorized
and FDA has implemented in other settings.
In light of growing evidence of threats to the public health, the
Administration urges Congress to strengthen Federal standards for non-
traditional compounding. Such legislation should appropriately balance
legitimate compounding that meets a genuine medical need with the
reality that compounded drugs pose greater risks than those that are
evaluated by FDA for safety and efficacy and subject to manufacturing
controls to ensure consistently high product quality. We recommend that
it recognize the appropriate State role in regulation of traditional
compounding, while authorizing Federal standards and oversight for non-
traditional compounders that produce riskier products. We look forward
to working with Congress in striking the right balance.
conclusion
Protecting Americans from unsafe and contaminated drugs is not just
an important responsibility of FDA--it is part of our core mission. To
fulfill our mission, we must be able to proactively identify dangerous
practices before they result in actual harm, and when necessary,
intervene to minimize the damage and to prevent future similar events.
Tragically, there have been 32 deaths to date associated with this
outbreak. However, we are hopeful that our actions thus far and the
ongoing investigation are preventing unknown numbers of further deaths,
which might have occurred had we and our partners not acted
aggressively after we became aware of the outbreak.
We look forward to working with Congress on legislation that will
balance the need to allow legitimate forms of traditional pharmacy
compounding with the need for adequate Federal oversight of higher risk
pharmacy compounding practices.
I am happy to answer any questions you may have.
The Chairman. Thank you, Dr. Hamburg.
Dr. Smith, welcome. Again, as I said, your statements will
be made a part of the record in their entirety. If you could
sum it up, I'd appreciate it.
STATEMENT OF LAUREN SMITH, M.D., MPH, INTERIM COMMISSIONER,
DEPARTMENT OF PUBLIC HEALTH, BOSTON, MA
Dr. Smith. Good morning, Senator Harkin and Ranking Member
Enzi and members of the committee. Thank you for having me here
today. My name is Dr. Lauren Smith, and I'm the Interim
Commissioner for the Massachusetts Department of Public Health.
I must begin by saying that my thoughts are with the
victims and their families of this tragic outbreak--some of the
poignant stories described by Dr. Bell. I know that the numbers
that represent those made ill and those who lost their lives
actually represent real people with real stories. That only
strengthens my resolve to ensure that no other families have to
suffer the heartbreak that these have.
As a mother, a pediatrician, and a public health leader, I
have devoted my life and career to protecting the health of
others. These events invoke in me the same outrage that you and
the rest of the public feel. For many of you, I know this hits
very close to home.
For nearly 2 months, our department, along with the FDA,
has conducted a joint investigation of the New England
Compounding Center, the source of the devastating fungal
meningitis outbreak. We have also investigated and shut down
NECC's sister companies. NECC knowingly disregarded sterility
tests, prepared medicine in unsanitary conditions, and violated
their pharmacy license, which endangered thousands of lives as
a result. NECC bears the primary responsibility for the harm
that they have caused with these actions.
I was given the responsibility as interim commissioner less
than 3 weeks ago to lead my department through this crisis. And
like you, I have been trying to put together the pieces of the
puzzle. First licensed by Massachusetts in 1998, NECC and its
owner, Barry Cadden, have been the subject of numerous
complaints resulting in a series of investigations by the State
and the FDA.
These investigations led the Board of Pharmacy to propose
reprimand and probation in 2004. This proposal was inexplicably
weakened in 2006, allowing NECC to continue to operate without
any disciplinary actions pending an independent evaluation of
its progress under a consent agreement. The Board of Pharmacy's
failure to take decisive disciplinary action in 2006 on these
complaints contributed to these tragic events.
In addition, in April 2006, the Board of Pharmacy staff
learned that the principal of PSI, the evaluator for NECC, had
been convicted of Federal crimes that resulted in 18 people
being blinded. However, the staff did not share this
information with the Board members before they accepted the
report from PSI indicating that NECC's compliance with the
consent agreement had been completed. These same staff members
failed to act on a July 2012 report from a Colorado Board of
Pharmacy that NECC had violated both Colorado and Massachusetts
pharmacy regulations. These staff members have been removed
from their jobs.
Poor judgment, missed opportunities, and lack of action
have allowed NECC to continue on this troubling path. We
acknowledge that some of these lapses were preventable, but,
clearly, all are unacceptable.
From the early days of this outbreak, the department has
acted swiftly and decisively. We secured a surrender of NECC's
license, shut down its operations, and secured a total recall
of NECC products. We moved to permanently revoke NECC's
license, as well as the licenses of the three principal
pharmacists who oversaw their operations. We also secured the
suspension of operations of Ameridose and Alaunus, which are
two other drug manufacturers also owned by Barry Cadden, which,
as I'm sure you know, have been found to have substandard
practices.
While taking these strong and necessary actions, we have
reexamined our own State regulations regarding compounding
pharmacies. Although our regulations are comparable to those in
most States, they clearly need to be strengthened to address
the realities of this evolving industry. On November 1,
Massachusetts enacted a series of emergency regulations to
bring greater scrutiny to this industry and require sterile
compounding pharmacies to report both volume and distribution
information to us.
In addition, licensed pharmacies will also have to report
when they are the subject of either a State or a Federal
investigation. We have also begun unannounced inspections of
all sterile compounding pharmacies. Teams are conducting those
inspections even as we speak.
To further strengthen our oversight over sterile
compounding pharmacies, we must also explore changes in State
law. We have created a special commission to review best
practices in other States and to identify stronger mechanisms
of oversight of pharmacies such as these in Massachusetts.
As we work to raise our standards in Massachusetts, we urge
Congress to act to strengthen the Federal oversight.
Congressman Markey's leadership on this issue is laudable, and
we hope this will address the regulatory black hole that exists
currently between State and Federal oversight.
As a pediatrician who has cared for acutely ill children
and their families for close to 20 years, I understand that
patients place a significant amount of trust in our healthcare
system. We must use these terrible events as an impetus to work
together as public health leaders and legislators to institute
reforms to restore this trust and ensure that something like
this never happens again. I know that we will keep the victims
and their families always in our thoughts as we work to
identify responsibility and to implement policies and practices
that will be both effective and lasting.
Thank you. I appreciate this committee's interest in this
matter, and I commend you for moving so swiftly to bring us
together to discuss it.
[The prepared statement of Dr. Smith follows:]
Prepared Statement of Lauren Smith, M.D., MPH
summary
For nearly 2 months, the Massachusetts Department of
Public Health has conducted a joint investigation of New England
Compounding Center (NECC) with our Federal partners at the Food and
Drug Administration (FDA) to determine what caused the devastating
fungal meningitis outbreak that has sickened hundreds and led to dozens
of deaths across the country. DPH has also been jointly investigating
sister companies Ameridose and Alaunus, Westborough, MA-based drug
manufacturers.
NECC knowingly disregarded sterility tests, prepared
medicine in unsanitary conditions and unlawfully engaged in
manufacturing, endangering thousands of lives as a result.
This testimony provides a chronology of events based upon
documents, reports, and e-mails recently reviewed, beginning with
NECC's licensure in July 1998. It is a troubling history.
The Massachusetts Department of Public Health has taken
swift and decisive actions since we became aware of the outbreak.
DPH secured a surrender of NECC's license, shut down
its operations and issued a total recall of NECC products.
Massachusetts sterile compounding pharmacies have
been required to attest under penalty of perjury that they are
meeting all State laws and regulations.
The Massachusetts Board of Pharmacy approved
emergency regulations to enhance oversight of compounding
pharmacies.
We have begun unannounced inspections of the State's
25 sterile compounding pharmacies to review how they function
when they are not aware that an inspection is scheduled.
We have named Christian A. Hartman, an expert in
pharmacy practice and patient safety, to chair a Special
Commission on compounding pharmacies. We will look at best
practices in other States, explore new ideas, and consider the
interplay between State and Federal authority.
We have removed three key employees from their jobs
due to their failures to act at key junctures.
Massachusetts will continue to do whatever we can, make
any changes, and identify any areas of new law to make sure something
like this never happens again.
______
Good morning, Chairman Harkin, Ranking Member Enzi, members of the
committee, thank you for having me here today. My name is Dr. Lauren
Smith, I am the Interim Commissioner of the Massachusetts Department of
Public Health and I welcome the opportunity to have this discussion.
I want to say from the outset that my thoughts are with the victims
and families affected by this tragic outbreak. As a mother, a
pediatrician, and a public health leader, I have devoted my life and
career to protecting the health of others. Have no doubt that these
events invoke in me the same outrage that you and the rest of the
public feel. The natural first question we all ask is ``How could this
possibly have happened?'' The necessary second question is ``What can
we do to ensure that this terrible situation does not happen again?''
For nearly 2 months, our Department has conducted a joint
investigation of New England Compounding Center (NECC), alongside our
Federal partners at the Food and Drug Administration (FDA), to answer
these questions.
NECC is a Framingham, MA-based pharmacy that compounds sterile
medications. It was identified as the source of the devastating fungal
meningitis outbreak that has sickened hundreds and led to dozens of
deaths across the country. For many of you, and for those with cases
among your constituents in particular, I know these losses hit close to
home.
NECC knowingly disregarded sterility tests, prepared medicine in
unsanitary conditions and unlawfully engaged in manufacturing,
endangering thousands of lives as a result. NECC bears the primary
responsibility for the harm they have caused with these actions.
I was given the responsibility as interim commissioner less than 3
weeks ago, to lead my department during this crisis. And like you, I
have spent the last several weeks trying to put together the pieces of
this troubling puzzle.
Although the majority of these events happened in the previous
administration and well before I came to the Department, I offer the
following chronology based on a review of documents and reports from
the time.
Let me begin by noting that by statute, the Massachusetts Board of
Registration in Pharmacy, supported by the Department of Public
Health's Division of Health Professions Licensure, has primary
responsibility for oversight of the practice of pharmacy in the
Commonwealth.
The Board of Pharmacy is an independent body, with 11 members
appointed by the Governor. The Board has the responsibility and legal
authority to license and regulate pharmacies and pharmacists. DPH staff
investigators, lawyers, administrators, and an executive director
support the Board's operations.
The Massachusetts Board of Registration in Pharmacy's interaction
with NECC began on July 16, 1998, when it obtained its initial license.
On February 2, 1999, the Board received the first complaint against
NECC, which alleged that the pharmacy had provided a prescriber with
pre-printed prescriptions that specifically listed NECC medications.
State law prohibits pre-printed prescriptions. Prescriptions are
required to be patient-specific, and based upon the patient's
diagnosis, medical history, allergies, tolerance, and the specific
constellation of symptoms that the patient is presenting. This
complaint was resolved in October 1999 with an informal reprimand
letter, a non-disciplinary action.
In April 2002, working with the FDA, the Board visited NECC and
obtained records related to a recent MedWatch report concerning
betamethasone, a compounded steroid suppository. The FDA investigator
met with Barry Cadden, owner of NECC, and conducted an inspection on
April 9, concerning procedures, sterility and recordkeeping.
In October 2002, the Board initiated a joint investigation with the
FDA at NECC related to the April 2002 betamethasone complaints as well
as MedWatch reports associated with the use of methylprednisolone
acetate, the injectable steroid medication implicated in this current
outbreak. The MedWatch reports pertained to two patients who received
the steroid and experienced pain and headaches and were hospitalized
with meningitis-like symptoms. Laboratory tests from these
investigations identified subpotency of betamethasone and superpotency
of methylpredni-solone acetate. The FDA also noted contamination of one
lot of methylprednisolone acetate with bacteria. These investigations
continued into 2003.
Also in 2002, Board of Pharmacy member Karen Ryle convened a Task
Force to study Board oversight of the compounding pharmacy industry.
Barry Cadden served on this Task Force, which met for nearly 2 years.
The Task Force discussed proposals to change regulations around
compounding, but records do not show whether formal recommendations
were made, and the Board did not adopt new regulations.
In February 2004, the Board conducted a followup inspection of NECC
and noted that all deficiencies surrounding sterility, safety, quality
and procedures from the 2002-3 investigations had been resolved. Just
weeks later, however, the Board received a complaint, from a pharmacist
in Wisconsin, expressing concerns with the safety of a topical
anesthetic product. The complaint alleged that NECC advised the
pharmacy to unlawfully use a staff member's name rather than an
individual patient's name in filling a prescription. The Board then in
place resolved this complaint with a disciplinary warning letter on
September 30, 2004.
Based on this series of investigations, in September 2004, the
Board voted unanimously to sanction NECC with a reprimand, a 3-year
probation, and a requirement that Barry Cadden obtain additional
training in sterile compounding. NECC objected to these sanctions, but
the Board reaffirmed this approach through an additional unanimous vote
on November 23, 2004.
More than a year later, on January 10, 2006, NECC entered into a
non-disciplinary consent agreement with the Board that was
significantly weaker than the earlier version. The signed consent
agreement stipulated a 1-year probation to be stayed with the condition
that NECC hire an independent evaluator. The Board's staff identified
Pharmaceutical Systems, Inc. (PSI) as the evaluator to conduct
inspections of NECC's compounding practices.
Despite interviews with Board and staff members involved with these
decisions and a thorough review of the limited records retained from
this period, troubling questions remain about what influenced the more
lenient consent agreement resolution, given NECC's track record. I will
not be satisfied until we know the full story behind this decision.
What we know now is that from January to April 2006, the
independent evaluator PSI conducted an assessment of NECC's compliance
with United States Pharmacopeia Standards, and oversaw development of
policies and procedures. PSI also issued recommendations for process
improvement and provided training for NECC staff. An April 7, 2006
report from PSI described NECC's compliance with the evaluation.
Our investigation has revealed that in late April 2006, some Board
of Pharmacy and Health Professions Licensure staff, including the
Board's executive director and legal counsel, learned that PSI
executives were convicted of Federal crimes related to defrauding the
FDA and selling unapproved sterilization equipment to hospitals.
However, we have found no evidence to indicate that the executive
director or staff attorney of the Board provided this crucial
information to the Board. Nor did they see fit to send inspectors back
to NECC in 2006 to determine if they were fulfilling the requirements
of the corrective action plan.
In May 2006, the Board voted to affirm that NECC was in compliance
with the terms of the consent agreement, thus accepting PSI's findings
in overseeing NECC's compliance.
Consistent with Board policy at the time, which was to inspect
pharmacies only upon a change in licensure status or upon receipt of a
complaint, the next time a Board investigator returned to the pharmacy
was 5 years later on May 24, 2011 to inspect NECC following its
renovation and expansion. This inspection included a full review of the
facility space, operations, sterility protocols, and compliance with
United States Pharmacopeia among other factors. The inspector found no
evidence to suggest that NECC was violating patient-specific
prescription requirements, and no deficiencies were cited.
In March 2012, the Board received a complaint pertaining to an
insufficiently potent eye anesthetic distributed by NECC. This
complaint focused on the potency of the medication but did not
reference sterility concerns. This investigation continues.
In July 2012, some of the same staff members who failed to inform
the Board of the issues surrounding PSI received a report from the
Colorado Board of Pharmacy documenting violations of Colorado and
Massachusetts pharmacy laws. The information provided to the Board
executive director and legal counsel by Colorado showed that NECC had
distributed bulk shipments of drugs to many hospitals in that State
between 2010 and 2012 without patient/specific prescriptions, in
violation of NECC's Colorado and Massachusetts licenses. The Colorado
Board of Pharmacy issued a cease and desist order to stop NECC from
engaging in the unlawful distribution of prescription drugs in the
State in April 2011. Colorado informed the FDA of the adverse action,
and provided them with the report, supporting evidence, and copy of the
order. However, there is no record of Colorado providing similar notice
to the Board or DPH.
Colorado contacted Board staff in July 2012 because NECC was
violating the April 2011 cease and desist order by continuing to
prepare and dispense bulk shipments without patient-specific
prescriptions. However, after receiving the July report, both the
executive director and legal counsel failed to order an investigation,
inform the Board of the complaint, or take any other action on the
Colorado complaint.
The first two lots of contaminated methylprednisolone acetate
linked to the meningitis outbreak were prepared in May and June 2012.
The Colorado report was received 2 weeks prior to the production and
shipping of the third lot of contaminated vials, which were prepared in
August. Though issues of contamination with NECC products were not
included in the Colorado report, given NECC's history and the evidence
from Colorado that the company was violating Massachusetts pharmacy
regulations, prompt action was warranted.
The individuals responsible for this failure to act have been
removed from their jobs. These steps are consistent with the swift and
decisive actions of DPH since we became aware of the outbreak.
Late in the evening of September 24, the Tennessee Department of
Health notified our Department about a cluster of six exceedingly rare
fungal meningitis cases. All six cases shared common risk factors,
including an epidural injection of a steroid prepared by NECC. The
Massachusetts DPH secured a list of medical facilities in 23 States
that had received shipments of the steroids from three suspect lots
identified by the Centers for Disease Control and Prevention. A day
later, we secured a recall of those three lots, totaling 17,676 vials,
and began our on-site investigation at NECC.
On October 1, we were joined on-site at NECC by the FDA and
commenced our joint investigation. Among a list of troubling findings,
investigators observed visible black particulate matter in sealed vials
that had been returned to NECC through the recall. Several batches of
the drugs had been shipped by NECC prior to the completion of internal
sterilization tests. Investigators also found evidence that NECC had
been dispensing medication in bulk shipments rather than filling a
patient-specific prescription for each dose dispensed.
We secured a surrender of NECC's license, shut down its operations
and issued a total recall of NECC products.
Our aggressive investigation not only focused on NECC, but also
companies with shared ownership. On October 10, we secured the
voluntary suspension of operations of Ameridose, a Westborough, MA drug
manufacturer also owned by Barry Cadden. This closure allowed for a
full investigation by DPH and the FDA, and eventually led to a total
recall of Ameridose products. Ameridose remains closed as the
investigation continues.
The Board of Registration in Pharmacy moved to permanently revoke
NECC's license, as well as the individual licenses of the three
principal pharmacists who ran NECC so they may never practice pharmacy
in Massachusetts again. The Board also issued a cease and desist order
to all pharmacy staff at NECC to bar them from any compounding
activities.
While taking these forceful and necessary actions, we have also
reexamined our own approach to regulating this industry.
It is clear that the compounding pharmacy industry has changed
drastically from the days of neighborhood businesses that served a
local clientele. We recognized that our State regulations needed to be
strengthened to address the realities of this industry, which has
evolved over time, and again we took action.
On November 1, Massachusetts enacted a series of emergency
regulations to bring greater scrutiny to the industry and ensure that
we have the tools to prevent such a tragedy from happening again.
Our new regulations stem from the lessons learned from this tragedy
and require sterile compounding pharmacies in Massachusetts to report
volume and distribution figures to the State, for the first time. This
will alert us to any pharmacy that is acting like a manufacturer by
producing medication on an industrial scale, which requires an FDA
license and the additional scrutiny and adherence to high manufacturing
standards for safety and quality that FDA oversight requires. We are
also requiring all licensed pharmacies to report to the State when they
are the subject of investigations by any other States or the Federal
Government. This will allow us to know when other entities have
identified issues with pharmacies in Massachusetts, including other
States that issue non-resident licenses to pharmacies in Massachusetts.
The Board of Pharmacy's prior approach to inspecting pharmacies
when they first apply for a license, and then again only if they move
or if there is a complaint, though not out of line with the approach
used by most States, is no longer sufficient to keep pace with the
changing nature of the industry. Since the outbreak we have begun
unannounced inspections of the State's 25 sterile compounding
pharmacies to review how they function when they are not aware that an
inspection is scheduled. Teams are in the process of conducting
additional inspections as we speak.
Massachusetts sterile compounding pharmacies have also been
required to attest under penalty of perjury that they are meeting all
State laws and regulations.
To further strengthen our oversight over sterile compounding
pharmacies, we need to explore changes to State law. We created a
Special Commission, and named Christian Hartman, an expert in pharmacy
practice and patient safety, as its chairman. The Commission will
include members of the Massachusetts' Legislature and experts in
pharmacy practice, regulatory affairs, and patient safety. We will look
at best practices in other States, explore new ideas, and consider the
interplay between State and Federal authority. The first meeting of the
Commission is scheduled for this month and this body will report its
findings to the Governor by December 31.
As we work to raise standards in Massachusetts, we urge Congress to
act to strengthen Federal oversight. It is clear that the patchwork of
disparate State regulations is not enough to keep the public safe.
Congressman Markey's leadership in putting forward legislation is
laudable and would help fill what he has aptly called a ``regulatory
black hole'' that exists between State and Federal oversight.
Congressman Markey's report also shows that at least 34 States have had
deaths or illnesses stemming from violations at compounding pharmacies
nationwide before this current meningitis outbreak. We join Congressman
Markey in supporting immediate Federal action.
As a pediatrician who has looked into the faces of children and
families at their most vulnerable moments, I understand the faith and
trust that patients place in our health care system. I would never have
contemplated that a medicine I might prescribe to my patients could
actually be the source of such harm. We must use these terrible events
as an impetus to work together, as public health officials and
legislators, to reaffirm the trust that has been broken by the
circumstances surrounding this outbreak.
I pledge to you that Massachusetts will continue to do whatever we
can, make any changes, and identify any areas of new law to make sure
something like this never happens again. We intend to identify
responsibility but also focus on reforms that will be effective and
lasting.
As the victims and their families remain always in our thoughts, we
accept the challenge of reform that lies ahead.
Thank you. I am happy to take your questions.
The Chairman. Thank you, Dr. Smith, and thank you all.
We'll start a round of 5-minute questions.
I wanted to have Dr. Bell here today. I know you weren't at
the hearing in the House yesterday. I thought it was extremely
important for us and for the public to know just how important
the intervention of CDC was in this. I'm going to read your
concluding remarks which I read last night.
``The outbreak demonstrates the essential role that
public health plays in identifying and responding to
infectious disease outbreaks, large or small. Our
national public health capacity is disseminated to
State and local responders who work on a daily basis to
keep our country safe from infectious diseases, whether
they are from naturally emerging threats such as a new
influenza pandemic or from human made problems such as
contaminated medicines. CDC will continue to work with
State partners, national experts, frontline clinicians
and others to respond to the critical public health
needs related to this outbreak.''
Again, I think the public needs to be aware that we have an
infrastructure in this country with CDC, with our State
departments of public health, with our field epidemiologists
who instantaneously can intervene, track these threats down,
keep our public safe. That's why I thought it was so important
for CDC to be here today, both to outline--and I know we have
another witness from Tennessee who will be here. You mentioned
this person, Dr. Kainer--to let the public know that things
happen, and we're never going to be 100 percent safe, either
from human-made problems or infectious diseases, as you
mentioned, like influenza pandemics.
I think it's also important for us to know that the more we
constrain the budgets of the Center for Disease Control and
Prevention and the budgets of our public health entities around
the United States, the more we put the public at risk. We have
for too long treated public health as sort of a stepchild of
healthcare in America, something that, well, we just don't have
to pay attention to. It's to our detriment, and people die, and
people get sick if we don't continue our support for public
health in the United States.
Senator Mikulski and I worked very closely in the
Affordable Care Act to make sure that we had a strong component
of public health in that bill. I just hope that my colleagues
and others who are watching the proceedings will, again, note
what has happened to public health funding in America. I know
this is not an Appropriations Committee meeting, but I wear two
hats, and I'm sorry, but I'm going to wear that one here right
now.
In fiscal year 2009, CDC funding was $6.239 billion. Got
that? In 2009, $6.239 billion. In fiscal year 2012, it's down
to $5.644 billion, and yet we have more emerging diseases. We
have more people. We have people moving more rapidly around the
country. We have people moving from this country to other
countries, back and forth, through commerce, through travel.
Yet we continue to turn a blind eye to the need for public
health infrastructure in this country.
Dr. Bell, thank you, and I look forward to our witness from
the State of Tennessee also and what they did to intercede in
this.
Dr. Hamburg, when I see the history of this and I read the
history of this and I see the two court cases, Fifth Circuit
and Ninth Circuit--I'm not going to go into all that. You
understand it. I have some sympathy for the FDA not knowing
exactly what its role is going to be. But that's OK. That's the
past. We have to do something now. And, of course, I'm going to
look to Senator Roberts and others who have been more involved
in this in the past for some guidance and direction.
Why don't we just have a demarcation line? If a compounding
pharmacy makes anything that goes outside the State boundaries,
that's FDA jurisdiction--anything. If it stays within a State,
it can be State or it can be dual, depending. But anything that
goes beyond State borders, that must be under FDA purview.
Dr. Hamburg. That isn't the way the law is currently
written. You're asking a larger question of why don't we do
that. The problem is----
The Chairman. I know that's not the way the law is, but I'm
saying why don't we do that?
Dr. Hamburg. The problem is that there is not a clear
distinction between what is a compounder and what is a
manufacturer, either in law or in practice. The industry is
evolving in ways that can be very, very important to the
healthcare system and the needs of patients.
For example, it used to be in a hospital that the hospital
pharmacy in the basement would make up intravenous bags with
potassium chloride or other substances added in to be used on
the floor. Because of volume and because of concerns about
making sure that this is actually done under the best and most
safe and most efficient circumstances, hospitals have started
outsourcing some of those kinds of activities where they're
repackaging a drug or a medical product, and that can have real
benefits.
If we treat all of those individuals as manufacturers,
we'll have to have them submit drug applications for every one
of those products. They'll be subject to user fees. We could
hold them to stronger standards of compliance to good
manufacturing practice, et cetera, and that would really have
benefits. I think the challenge is we have to think about how
to address this.
The Chairman. Dr. Hamburg, I understand. I get all that.
But, really, the essential thing is what is in the best
interest of protecting the public health.
Dr. Hamburg. I think----
The Chairman. That's the essential question.
Dr. Hamburg. Yes.
The Chairman. Now, if some people can't protect the public
health by making things in their basement, maybe they shouldn't
be making things in their basement.
Dr. Hamburg. I guess what I would really propose is that we
have an antiquated system, trying to fit a square peg into a
round hole. What we have proposed in terms of a tiered system,
I think, could get at these issues in a very responsible way.
Traditional compounding on a small scale would remain under the
purview of the States.
Nontraditional compounding that gets us into this area
would be addressed in a different way. For one thing, they'd
have to register with us, so we'd know who they were and what
they were making. We would have Federal standards that they
could be held to, either enforced by the States or by the FDA.
We would have to, in statute, through a combination of factors,
define what puts you into this category; what kinds of products
you're making, like sterile products; what volume of products;
are you shipping interstate; other issues about shipping
directly to the user or through a third party. We can do that
together.
Then there's some products that clearly should only be
under the purview of a full-fledged manufacturer and that
simply should not be compounded because of the nature of those
products, biologics and transdermal patches, extended release,
and other things. Then copying an FDA-approved drug is also
clearly not appropriate.
The Chairman. OK. Thank you. I'm over my time. I will hold
for Senator Enzi when he returns.
Next I would recognize--oh, he's not coming back? Then I
would yield to Senator Roberts or Senator Alexander. This is in
terms of how people appear on the committee. Senator Roberts
appeared----
Senator Roberts. It looks like I have appeared first.
Dr. Hamburg, your past interactions with NECC, the New
England Compounding Center, prior to the current crisis, which
spanned over 6 to 10 years, depending on how you look at it--we
were taking a look at your testimony before the House. Were you
Dingellized over there or, did you get around all that?
Dr. Hamburg. That's a term I'm not familiar with.
Senator Roberts. There are a lot of us that are very much
familiar with it.
[Laughter.]
You said that NECC has repeatedly disputed FDA's
jurisdiction over its facility. You cited a number of times
during your interactions that NECC had done so. Isn't it also
true that each time the NECC disputed the FDA authority, the
FDA responded, reasserting its authority to regulate the NECC?
Now, that culminated in the final communication between the FDA
and the NECC in 2008 prior to the current crisis.
The FDA wrote to the NECC to outline in no less than four
pages--and we don't need to get into reading the four pages, I
hope--the numerous reasons why the FDA did have the authority
to regulate and, furthermore, use its enforcement authorities
with the NECC. I think that's correct.
Now, in fact, that letter went on to tell the NECC not only
to clean up its act or there would be specific consequences,
but also to confirm future inspections would occur to ensure
the firm's compounding practices are consistent with the
policies articulated in the compounding guidelines. If this is
correct, then I think we need a yes or no answer from you. That
didn't come in the House. One more time, did the FDA actually
have the authority to regulate and engage in enforcement
actions against the NECC? Can you give us a yes or no?
Dr. Hamburg. I'll make you mad the same way I made Dingell
mad in terms of it's not a yes or no question, per se. We have
authority, but it's limited and----
Senator Roberts. I think you said it was a gray area. I
don't want a gray area. I want a black or white answer. Do you
have that authority? Did you have that authority?
Dr. Hamburg. We have limited--we have authority, but it is
limited and unclear and contested.
Senator Roberts. That's a hell of an authority. In May
2011, from the Colorado Board of Pharmacy, the FDA was informed
of a cease and desist letter and related report accusing the
NECC of illegal distribution of compounded drugs. FDA
officials, including Bruce Ota, the signatory to the 2008 FDA
letter I was referring to, to the NECC threatening enforcement
for such conduct and asserting jurisdiction over NECC, was
individually notified according to the May 2011 email that was
introduced into the record.
The FDA then waited until July 2012, over a year, to
suggest to Colorado they contact the Massachusetts Board of
Pharmacy. I don't know how you can explain this, with over a
year. The State of Massachusetts fired and suspended the
individuals who ignored the Colorado complaint about the NECC.
By the time the FDA suggested in July 2012 that Colorado
contact the Massachusetts Board for action, the NECC had
already compounded some of the drugs that led to this tragedy.
Indeed, if the FDA had acted in 2011, according to their
letter, either to investigate or to notify Massachusetts of the
NECC's continued violation, 30 lives could have been saved. Did
the FDA take any action against the FDA personnel who ignored
this problem for over a year?
Dr. Hamburg. Obviously, in the context of the situation,
looking at that, questions are raised. When the communication
came from Colorado, it was around an issue of NECC acting out
of compliance with the Colorado Board of Pharmacy Registration
and Licensure and the question of whether they were, in fact,
registered with us as a manufacturer.
I wish, in retrospect, that we had alerted the
Massachusetts Board of Pharmacy at that time. It's also
important to underscore that that communication really was not
about the kinds of sterility concerns and safety quality issues
that underlie this ongoing outbreak.
Senator Roberts. OK. I appreciate that. My time is almost
up. If you had inspected upon receipt of the Colorado complaint
in the summer of 2011 and found the unsanitary conditions and
the scale of production that existed at NECC, is it your
position that you could not have shut the operation down
despite a decade of evidence that NECC was a bad actor? That's
the first part.
Last part: If that is the case, why do you assert the
authority to cease, enjoin, or otherwise prosecute the
recipients of your warning letters? Why in the hell send the
warning letters if you can't act on them? That's just an empty
threat. Why do we even have an FDA and why do you have a job if
the FDA can't stop back-alley, large-scale drug manufacturing
that it knows about and writes letters about?
Dr. Hamburg. If we had gone in in 2011, as you had
suggested, and found unsanitary conditions and contaminated
product, we could have acted with the full force of FDA
authority as we have acted in other cases of compounding
failures that have resulted in contaminated products. However,
in terms of our routine oversight responsibility of NECC, that
does rest with the State board of pharmacy if they are behaving
as a compounder.
Massachusetts was actually in that facility in 2011 and
found that the conditions were satisfactory. It speaks to the
fact that inspections are only one piece of what can make a
difference. What we are really trying to seek is a legislative
framework that would enable us to hold these kinds of large-
scale, nontraditional compounders to a set of standards,
proactively in a preventive way, rather than using authority--
--
Senator Roberts. That's what you want us to provide, a
legislative framework to really define that you do have the
authority to act on your own letters?
Dr. Hamburg. At the present time, our authority, because it
is limited and unclear and contested, really forces us into a
position of being reactive rather than proactive. With drug
manufacturers, we can require and hold them to a different set
of standards in terms of compliance with good manufacturing
practice and the requirement of preapproval review for safety,
quality, and manufacturing controls.
Senator Roberts. Thank you. I'm done.
The Chairman. We've got to go around. Thank you.
Senator Mikulski.
Statement of Senator Mikulski
Senator Mikulski. Mr. Chairman, thank you very much for
holding this hearing. I, too, wish to express my condolences to
the families who have passed away--one in Maryland. Today,
their Sun paper reports a constituent whose name I can use
because it's already in a public domain--Mr. Gerald Cohen, 71,
retiree, filling his free time with gardening, enjoying the
company of his grandchildren, and being active in the
community. Treated with steroids, he now is so sick from
nausea, fever, and he eventually had a stroke. He told his
wife, ``I thought I was dying.''
This is why we are here today, to look for the right
regulation. Also, at the same time, regulation without
resources is a hollow exercise, and then resources without a
workforce--the fact that we have to recruit people in science
and train them to enforce these also needs to be part of this
discussion.
Mr. Chairman and colleagues, I hope this is the first of a
series of hearings on not only regulatory reform but also on
resource need and also on workforce need. I would hope today,
too, we would look at not only what is not working but what did
work. Obviously, Tennessee was really doing their public health
job. Obviously, Colorado was really doing their job, because
they sent an alert. So, we need to do those lessons learned.
In the area of regulation, I'm very interested in the black
hole of when do we go from the traditional role of
compounding--with Senator Roberts we all agree exists--to where
they're now manufacturers. Even when they do do traditional
compounding, when are they just sloppy, dilatory, or dangerous?
How do we get to that? The other is then the resources that
Senator Harkin talked about and referenced.
Dr. Hamburg, I'd like to come back to you. Do you feel that
what you are suggesting with your two-tiered system would get
us to the problem, or would you also think that there needs to
be--that this would be a down payment on getting to this? As
the market is evolving, market forces are evolving on
compounding, and then our tendency in Congress is to be anti-
regulatory, dump everything on the States, until there is a
problem. Then we pound our chests and want the Federal
Government to be involved.
We've got a lot of convergent forces, even within this
institution. Do you think your framework would get us to this,
or do you think also we need additional work, say, through a
commission, as suggested by Senator Roberts, or through the
Institute of Medicine to go for an even more deep dive in this?
Dr. Hamburg. I think that the tiered approach that we are
proposing would make an enormous difference. Right now, really,
what is a compounder versus a manufacturer is very unclear.
503A was Congress' attempt to really clarify it, but it doesn't
define compounding anywhere. It doesn't set an absolute limit
on volume. It doesn't set an absolute prohibition on
compounding in advance of getting a prescription.
Senator Mikulski. That's the methodology. What would be the
outcome achieved?
Dr. Hamburg. What would be the outcome achieved?
Senator Mikulski. In other words, if we go your way, yes.
Dr. Hamburg. Oh, I think there would be many, many
benefits. We would, No. 1, be able to really know what the
landscape looks like, who's out there doing what. We would have
a set of Federal standards that would be strong and really
support quality. We would have authorities for adverse event
reporting and an ability to have labels so people would know
whether the product was compounded or not. We would clarify the
issue around inspections so that when we went in, we'd be able
to get access to the records that we need.
Senator Mikulski. OK. Thank you. I want to go to Dr. Bell
and Dr. Smith for my next set of questions.
Dr. Bell, you referred consistently in your testimony about
something called the Epidemic Intelligence Service, and then
how also those people trained in that service are working in a
variety of States, one of which was Tennessee that, again, did
such a superb job.
Senator Alexander, we'd like to compliment the public
health people in Tennessee.
Could you, then, talk about the role of CDC, not only in
this, but this Epidemic Intelligence Service, and how it would
be of use in terms of ultimately bio surveillance at the local
level which acted so quickly, because we can't be in every
place, everywhere, all the time? And it must go through the
States.
Dr. Bell. Yes. Thank you, Senator. The Epidemic
Intelligence Service is a training program that CDC has had in
place for actually many decades. Many of us--and I hazard to
say maybe most of us, even me with the gray hair--who have been
at CDC for decades started our careers in CDC in the Epidemic
Intelligence Service. There is a very, very large cohort of
epidemiologists in the State and local health departments who
also trained at CDC.
This is an extremely important resource that we have. There
are other aspects----
Senator Mikulski. Just tell me what it does.
Dr. Bell. Basically, it's a training program, so----
Senator Mikulski. What do you train them to do?
Dr. Bell. We train them to do field epidemiology. We train
them to investigate outbreaks. We train them in how to work
with the laboratories. We train them in how public health
works.
Senator Mikulski. Then they don't stay at CDC. Some do.
Dr. Bell. That's correct.
Senator Mikulski. Like the ones who were so pioneering in
the work on early detection of Legionnaire's Disease and
others. But then they go to States.
Dr. Bell. That's right.
Senator Mikulski. Then they work in State health
departments or in a variety of other areas of the public health
human infrastructure.
Dr. Bell. That's right. In fact, we have some Epidemic
Intelligence Service officers that are assigned to State health
departments during their training. For example, this outbreak
is a good example of how this EIS program works.
Senator Mikulski. I have limited time, Dr. Bell.
Dr. Bell. OK. Just to say that we have done what we call
Epi-Aids. These are, in outbreaks, assistants that we provide.
In this situation, we've sent EIS officers out five or six
times to help quickly--including to Tennessee very early on in
the outbreak--to help the State health departments quickly
identify the problem.
Senator Mikulski. Now, tell me how much these people get
paid, and what is their education?
Dr. Bell. I can't tell you how much they get paid. They
generally----
Senator Mikulski. Are they GS-15s? Do they get paid
$180,000 a year? Do they get paid $45,000 a year?
Dr. Bell. I think it depends on their level of training.
They have to have an advanced degree. It could be a Ph.D., an
M.D., or they could be a nurse with a master's degree. They
could be a veterinarian. They could be a pharmacist. They have
many different ways of entering CDC.
Senator Mikulski. Thank you. My time is up.
I would like to say to my colleague, Mr. Chairman, with
your indulgence--to my colleague from Kansas, Senator Roberts--
I would like, really, Mr. Chairman, to work with you to--we
have the FDA recommendations. We have the Roberts Commission. I
remember when you did that during the Affordable Care Act, and
it was an impressive piece of work.
We're possibly going to IOM, the Institute of Medicine,
where we have the appropriate regulation, where we don't over-
regulate so we strangulate. But at the same time, we have to
really move on it. While we're working to pass legislation,
perhaps we need a process to get us to the right legislation
and maybe a down payment on what we need to do, while we also
look at the resources, which you identified, Mr. Chairman, and
then these workforce needs, because if you have the right roles
without the right people, you don't have anything.
Thank you, and I appreciate this hearing.
The Chairman. I want to reassure you, Senator Mikulski, and
others on this committee that I have asked my staff to work
with Senator Enzi's staff and other staff on this committee to
get a good bipartisan process going, to work together to
achieve exactly the end that you say. That is ongoing right
now. I want to reassure you of that.
Senator Alexander.
Statement of Senator Alexander
Senator Alexander. Thanks, Mr. Chairman, for the hearing,
and thanks to Senator Roberts for your leadership in the area.
I certainly intend to work with Senator Harkin and Senator
Roberts, Senator Mikulski and others.
I hope it's our first order of business to answer these
questions, not just whose job was it to prevent this tragedy,
but whose job will it be to make sure it doesn't happen again.
That's our job here today. This has been a nightmare for
Tennesseans, as it has been for any Americans affected. We've
had 32--13 Tennesseans died, 81 Tennesseans are sick, and 1,000
more exposed.
All of us are shaken, because we live in this country where
we have this miracle that we walk into one of our 60,000 drug
stores or pharmacies or go to our doctor or our pain clinic,
and we get medicine, and we don't think about it. We just
assume it's safe. And then to suddenly go home and find that
you've got fungal meningitis and you may die or be permanently
disabled is a nightmare, not just for the families involved,
especially them, but for all of us. I want to do everything I
can to help solve this problem.
Now, my experience as Governor, Mr. Chairman, was that
whenever I gave a job to more than one person, sometimes it
came back not done. When I put somebody on the flagpole, it was
surprising to see how fixing that responsibility got it done.
Let's start on what went right.
Obviously, we had incompetence in the Massachusetts State
Board of Pharmacy. We had confusion at the FDA. We had a
textbook case of A-plus excellence at the CDC, the Centers for
Disease Control, and at the State of Tennessee and at
Vanderbilt University, their partner, where they uncovered this
within literally a matter of a couple of days, and in a few
more days were able to alert everybody about it.
Dr. Bell, whose job is it? Is it your job at CDC, once
something like this is discovered, to let the world know about
it? Is that your job, or is that the job of a lot of different
people?
Dr. Bell. Senator, that's our job.
Senator Alexander. So it's clear. If that hadn't been done,
that would have been your responsibility, really. Right?
Dr. Bell. Yes, sir. It's our responsibility to let the
world know about public health threats.
Senator Alexander. Right. And you did a superb job. Let's
go back. What we're hearing from the FDA is they had some
authority, but it was confusing. We hear from Massachusetts--or
I'll just say it. Massachusetts--well, let me ask Dr. Smith.
Massachusetts clearly had the authority to regulate this
compounding pharmacy. Correct?
Dr. Smith. That's correct.
Senator Alexander. So Massachusetts clearly had the
authority. FDA had some authority, but there was confusion. It
seems to me that one guiding principle in terms of working this
out is let's stop this dual responsibility. Let's put either
the State board of pharmacy on the flagpole or the FDA on the
flagpole and get the other one out of it.
Now, I'll give you an example of that. In surface mining,
we have a procedure in the State where the EPA and the
Department of Interior may delegate to States the whole
responsibility for regulating surface mining, or they may take
it back. If something bad goes wrong, and Tennessee has that
responsibility, it's Tennessee's fault. If Tennessee gave it
back to the Federal Government, it's the Federal Government's
fault. At least everybody knows who's on the flagpole for that.
Dr. Hamburg, would you be in favor of a system that would
say to a State like Massachusetts that for 10 years has been
incompetent in managing a compounding facility like this that
it should take over completely compounding of pharmaceutical
drugs?
Dr. Hamburg. There are many different models that----
Senator Alexander. No. I'm asking you would you be in favor
of that model? Do you think it makes sense to have a model
where you may delegate to Massachusetts or any State, for
example, the responsibilities for even sterile compounding or
advanced com-
pounding, or you may keep it?
Dr. Hamburg. I think first----
Senator Alexander. But if you kept it, it would be your
responsibility, and you couldn't say you were confused about
it.
Dr. Hamburg. Traditional compounding on the local level
should remain the responsibility of States. Nontraditional com-
pounding----
Senator Alexander. How much of that goes on? Traditional
compounding, as I understand it, happens in most pharmacies. Is
that right?
Dr. Hamburg. Most pharmacies. We don't know the numbers
because they don't register with us. There are many, many,
many, many thousands.
Senator Alexander. I've heard an estimate of 60,000
pharmacies or drug stores.
Dr. Hamburg. Yes.
Senator Alexander. That's traditional compounding. Advanced
compounding--how much of that is there?
Dr. Hamburg. We think there are about 7,500 pharmacies
doing so-called advanced compounding, and then about 3,000 that
are doing sterile processing. For those, we should have Federal
standards that could be enforced by the State or by the Federal
Government.
Senator Alexander. Now, that's my problem. Why would you
say ``or by the Federal Government?'' Then we have a hearing 5
years from now, and we have another tragedy, and the State
says, ``Well, we could have done it,'' and you say, ``We could
have done it.'' I'd like to see one of you say, ``It was our
job,'' just like Dr. Bell said.
Dr. Hamburg. I guess I'm saying that's a subject for
discussion. Some States are very strong in terms of their
boards of pharmacy. Others are much weaker.
Senator Alexander. How do we pick and choose? If I'm
sitting down in Gainesboro, TN, I don't care which one it is.
Whether it's the Federal Government or the State government, I
want the one that's going to do the job. How do you decide
that?
Dr. Hamburg. I think it should be made explicit.
Senator Alexander. So you agree that one person should
have----
Dr. Hamburg. I do think we should make it explicit.
Senator Alexander. With advanced compounding, either
Federal or State should be in charge. Is that right?
Dr. Hamburg. For nontraditional compounding, there should
be Federal standards that apply to certain types of practices
that go to issues of quality and safety.
Senator Alexander. Instead of telling somebody else what to
do, why don't you just do it? Is it too big a job to put all
here?
Dr. Hamburg. It would certainly enormously expand what we
do presently. We've got about 5,600 drug manufacturers and
facilities that we routinely are responsible for oversight of
and inspection.
Senator Alexander. Let me answer my own question and say
it's too big a job to put it all here. Would you then certify
State agencies as adequate to do sterile compounding or
inadequate to do it? And what if they fail to do it?
Dr. Hamburg. We need to discuss the range of options. That
would certainly be one model that could work. I would like to
see, though, some consistency of the standards applied, and I
think a Federal standard would enable us to do that.
Senator Alexander. Thank you, Mr. Chairman.
The Chairman. Thank you. I just want to say we will have a
second round here for this panel.
Senator Hagan.
Statement of Senator Hagan
Senator Hagan. Thank you, Mr. Chairman, and thank you and
Senator Enzi for holding this hearing today and the continued
bipartisan leadership of this committee. I also want to thank
our witnesses for coming today, and I certainly have heartfelt
and sympathy condolences to all of the families and individuals
who have gotten sick from this, ultimately have died, and then
all of the other people who are very worried about what might
happen.
Confronting this outbreak is a pressing national concern.
Over 451 people in 19 different States have developed fungal
meningitis, and 32 people have died, one of those individuals
in my State, a woman, Elwina Shaw. I actually had an
opportunity to speak with her son and with her husband. She was
77 years old. She was very active. Her husband said you
couldn't slow her down. She was busy from the morning until she
went to bed--active. She loved to garden. She had back pain
this summer. She went to get treated and had three steroid
injection shots. When she ended up getting a migraine headache,
she just didn't know what to do. She had nausea, and she really
just wanted to stay in bed.
She went to the hospital, and they treated her for
migraines. The headaches returned. Her family took her back,
and that's when they diagnosed the fungal meningitis. She
stayed at the hospital for over a month. She then had two
strokes. She was left without speech and motor functions. Her
son, Scott, said this was a horrible death, that she had black
fungus that had to be swabbed from her mouth and suctioned, and
it was just a horrible situation.
Fifty-two days after the injection to relieve her back
pain, she passed away. What is really ironic about today--today
would have been her 78th birthday. We all know that these are
terrible situations, and we are committed to acting to be sure
that something like this never happens again in the United
States.
Dr. Hamburg, what I'm trying to understand is--if you can
help give some thought and guidance to--why in February 2003
the FDA designated the New England Compounding Center a
pharmacy rather than a manufacturer? The investigation then was
into the same pharmacy compounding the same drug that led to
the same result of fungal meningitis. I'm just wondering if
this scenario could have been avoided 10 years ago.
Dr. Hamburg. We were actively involved in the investigation
beginning in 2002 of the contaminated products, working to get
the products off the shelves and limit the damage. In terms of
the ongoing efforts to remediate the sterility concerns, we
were working with the State board of pharmacy. Together we
determined that NECC--as I understand it. I, of course, wasn't
commissioner at the time, so I'm relying on records and what
I've been told.
As I understand it--and I've looked at the notes, the
minutes of the meeting--there was a determination that NECC was
behaving as a compounding pharmacy, and under the existing
legal framework, that is the appropriate authority of the State
board of pharmacy for regulatory oversight. They took the lead
and began a series of steps with NECC to address the sterility
concerns. We tried to be as helpful as we could be. It was
clearly determined that it was the Massachusetts Board of
Pharmacy's responsibility to work with NECC on this important
issue.
Senator Hagan. We certainly see what has happened in the
interim. That's why we're obviously holding this hearing and
looking at the actions that we need to take. And I know we're
on a short timeframe today.
Dr. Smith, I wanted to also thank you for coming. I know
you recently became the interim commissioner. Given the
integral role that the Massachusetts Board of Pharmacy has
played in the current outbreak, I want you to shed some light
on its failure to properly discipline the New England
Compounding Center over a longer period of time.
Yesterday, when I spoke to Elwina Shaw's son, Scott, he
said, ``These companies are allowed to make drugs in the back
end of a recycling facility?'' The disturbing thing is--and
this is his quote--is that ``someone in this Nation thought
that was a good idea. It makes no sense.''
I have to ask you, Dr. Smith, why in April 2011 did the
NECC receive a permit to expand its facilities when the FDA
later found out that its building was 100 feet from the
mattress and plastics recycling plant, and that black
particulate matter near the HVAC system was contaminating
sealed vials of the steroid now causing this current meningitis
outbreak? When the Board granted that request, did it know that
the same family that owns NECC also owns that recycling plant?
Any comments?
Dr. Smith. Certainly. When the board of pharmacy did the
on-site inspection that you're referring to, it was in the
situation of NECC requesting an expansion or a change in its
physical plant. The inspector at the time did the on-site
inspection, looked at about 10 or 12 different areas, including
sterility, quality assurance, staff training, among a number of
others. At that time, the inspector's report, which I know
we've shared with this committee, indicated that there were no
issues.
Now, it is not a specific aspect of the report to look at
the broader outside environment and the siting of the facility.
However, going forward, that is certainly something that we can
look at.
Senator Hagan. But in the FDA report, it did show that this
black particulate matter was close by and, obviously, could
have tainted some of the medicine.
Dr. Smith. There were a number of substandard practices
that NECC had, including the interior contamination that you're
discussing, as well as a disregard for their own policies and
procedures regarding sterility, and, obviously, their disregard
of Massachusetts pharmacy law.
Senator Hagan. Obviously, there are many issues that we
have to determine, and I appreciate you holding this hearing.
Thank you.
The Chairman. Thank you, Senator Hagan. As I said, we'll
have an extra round for Senators to followup on.
Senator Blumenthal.
Statement of Senator Blumenthal
Senator Blumenthal. Thank you, Mr. Chairman. I want to join
in my thanks to you and Senator Enzi for holding this hearing
as I suggested and urged that you do in the wake of this
tragedy and express my sympathy to the families and individuals
who have been affected by it, and also my respect for
Commissioner Hamburg and the excellent institution that you
lead.
Unfortunately, having reviewed many of these documents,
having spoken to experts in the field, having reviewed the
history here, the conclusion is inescapable that this tragedy
could and should have been prevented by more effective
enforcement of existing laws. NECC was a known risk to both
Federal and State regulators, but both failed to take any
dispositive and effective action to stop this kind of tragedy,
action that could have been taken against both NECC and
Ameridose. In effect, they were disasters waiting to happen. In
fact, they waited to happen for about a decade.
Going through the history, I understand your view that the
FDA's authority was, as you have said--and I think you've used
this formulaic expression a number of times--contested,
limited, and unclear. But so is a lot of Federal authority and
State authority, and it's used effectively to prevent
wrongdoing and law breaking by companies like NECC that cannot
only imperil the health of people but actually kill them, as
this company did through its contaminated product.
I think that a lot of the questioning that you're seeing
here reflects a skepticism on the part of Congress and the
public about whether the FDA will use this enhanced authority
more effectively than it has used the authority that it has had
to date. I think that the assurance that the FDA now has to
give is that it will be vigorous and zealous in using new
authority, if it's given that authority, and I think that that
is a challenge for the agency at this point.
It's a challenge for the Federal Government and certainly
for State authorities as well. We don't have jurisdiction over
them. I would suggest to you that the jurisdictional question
ought to be resolved very simply and starkly. If a company
manufactures drugs, you regulate them now, do you not?
Dr. Hamburg. Drug manufacturers we regulate, yes.
Senator Blumenthal. Correct. In other words, if a company
produces pharmaceutical drugs without a specific patient
prescription, they are regulated by the Federal Government.
That ought to be the rule.
Dr. Hamburg. As I understand it, that is not currently, in
fact, in the law.
Senator Blumenthal. It certainly was the intent of
Congress. Those decisions that so swayed the FDA to avoid
asserting its authority and jurisdiction were also unclear,
limited, and contested. An enforcer knows, in that situation,
the only way to protect the public is to use what authority he
or she has.
Dr. Hamburg. Yes.
Senator Blumenthal. In this instance, whether it's in 2004,
the inspection report that involved the FDA; 2006, where a
warning letter was issued and NECC never responded until 2007
and then the FDA never got back to them until 2008, the FDA
failed to use its existing authority. I'm suggesting to you
that the jurisdiction ought to be asserted as widely and
effectively as possible and that there be no ambiguity in the
law as there is now.
To the extent you use a multi-tiered, complicated,
differentiated approach, you will embark on the same kind of
perilous voyage that you have in the past.
Dr. Hamburg. If I can make two quick points, one is I
completely agree with what you're saying. Frankly, I wasn't
there, but I wish that the responses had been more timely,
there had been better communication with the States, and that
the outcome had been different. As far as using our existing
authorities, during my tenure, we have tried to be proactive or
aggressive in responding to problems that come before us.
There have been a series of incidents where we've had
problems with contaminated products for intraocular injection
or problems with other compounded products, and we have moved
in quickly, as soon as we heard about the cases, done the
inspections, gotten the companies to recall the products. In
some cases--in most of the cases, in fact, they've stopped
compounding sterile products.
In one instance that was actually a veterinary case that
occurred right before I became commissioner, we decided to go
after the compounding pharmacy after 21 horses were killed
because of super potent medication that they were provided with
by a compounding pharmacy. We lost in court. Later, we had a
problem with that same compounding pharmacy for an important
human medical product, and there was serious injury as a
result. We went back in, we recalled the product, we got them
to stop practices, and they're not compounding now.
We have tried to use the authority that we have, but it is
reactive. What I would like would be to have a system in place
that was statutorily defined, that would assign roles and
responsibilities, that would define standards of quality
practice, that would help us to prevent problems from happening
in the first place. Just looking at the map in terms of how the
statute governing our oversight of compounding pharmacies
currently exists, it applies in some parts of the country and
it doesn't in others, and there's a big gray area. That can't
be good for anyone.
What I'm saying is that--as Senator Roberts said, this is
certainly the most tragic of the events that we've seen. For
more than a decade, there have been problems in this area, and
there will be more problems unless we really work together, to
make sure that we have the overriding, legal authorities that
are strong and clear and explicit. I just think we can do
better.
Senator Blumenthal. I agree.
And I apologize, Mr. Chairman, because my time has long
expired.
Overriding is the key word, overriding local authorities
that may be reluctant to enforce. Your job--and it is uniquely
and always the job of the Federal Government to establish
standards that protect the public health and safety where there
is a national impact, and, clearly, there is a national impact
here. When a drug compounding pharmacy--whatever terminology
you want to use, traditional, nontraditional, big, small--if
they manufacture a drug, if they make it without a specific
individual prescription, that's manufacturing. You do that now.
Why not for these as well?
Thank you, Mr. Chairman.
The Chairman. Thank you very much, Senator Blumenthal.
I will, for the record, say that the first phone call I
received after this outbreak occurred was from Senator
Blumenthal, urging us and urging this committee to really
engage in this. Based on that, we got our committee staff
involved in it immediately.
I thank you for your diligence and being on top of this,
Senator Blumenthal.
Senator Blumenthal. Thank you, Mr. Chairman.
The Chairman. Senator Bennet.
Statement of Senator Bennet
Senator Bennet. Thank you, Mr. Chairman. I want to thank
you and the Ranking Member for holding this hearing.
This may be the most needless tragedy that I've seen since
I've been here. I've appreciated the work that we've done over
the last several years with the FDA to try to figure out how we
get a drug supply in this country that's actually safe. When I
learned, for example, that 80 percent of the active ingredients
in our pharmaceuticals are coming from abroad and there was no
regulatory framework in place, we all went to work on that.
We're working together, and I appreciate the chairman's
leadership on a track-and-trace system in this country.
This was an event that never had to happen. I wanted to ask
a question to Dr. Smith and Dr. Hamburg about this.
Thank you for being here today. Thank you all for your
testimony.
Dr. Smith, as you relayed in your testimony, the Colorado
Board of Pharmacy issued a cease and desist letter to the New
England Compounding Center in both April 2011 and July 2012,
twice, because NECC had continued to violate its licensure in
both Colorado and Massachusetts by issuing numerous compounded
drugs without patient-specific prescriptions. Both times, our
board of pharmacy in Colorado also informed the Massachusetts
Board of Pharmacy, as well as the local Denver office of the
FDA.
I've been informed that upon receipt of both complaints,
the executive director of the Massachusetts Board failed to
assign an investigator to this complaint. After the outbreak,
they also failed to alert the Massachusetts Department of
Public Health officials of this complaint. Obviously, our State
had the diligence and resources to be on the lookout for NECC
products. Others, for some reason, did not and as a result this
tragedy occurred all over the United States of America.
Dr. Smith, I want to know whether you felt the response to
the Colorado Board of Pharmacy was adequate, and, if not, how
you're going to fix this problem going forward.
And, Dr. Hamburg, I'd like to ask you about when a State
board of pharmacy serves in its good actor role by issuing
these cease and desist letters and notifies the Massachusetts
Board and their local FDA office, how we can better prioritize
this at the Federal level. As Senator Alexander said, how can
we better strengthen the role of either the States or the
Federal Government to take responsibility in a circumstance
like this one?
Dr. Smith, I'll turn it to you.
Dr. Smith. Thank you. Just to be clear, while the executive
director of the Board of Pharmacy did receive notification from
the Colorado Board of Pharmacy regarding the cease and desist
that was done in April 2011, we have not found any record that
there was any communication from the Colorado Board of Pharmacy
at that time back in 2011.
Now, that said, clearly, when we got the information from
the Colorado Board of Pharmacy in July----
Senator Bennet. I don't think I understood what you just
said. Can you say that again?
Dr. Smith. I'm sorry. If I heard you correctly, you
indicated that back in 2011 and then again in 2012, the
Colorado Board of Pharmacy communicated with the Massachusetts
Board of Pharmacy. What I was saying is that we haven't found
any record of a communication between Colorado and the
Massachusetts Board until July 2012.
Now, that said, it is clear that it was a serious and,
grave lapse of judgment executed by the board's executive
director not to followup on what Colorado sent. The report was
clear. It indicated with sufficient detail that NECC was
clearly operating outside of Massachusetts pharmacy laws. The
board certainly knew of NECC at that time and that it had
issues. It should have been a red flag that was followed up on,
and it wasn't. That clearly was, frankly, a mistake, a grave
one, and we have acted since then to remove that employee.
Senator Bennet. It's one of those things where it doesn't
even feel like it's a gray area. It feels to us like it was a
flashing red light.
Dr. Smith. I agree. What I can say is when I learned of
this email exchange and the fact that we, the board of
pharmacy, knew this in July 2012, I was astounded, baffled, and
incredibly angry, because that was something we should have
acted on.
Senator Bennet. Dr. Hamburg.
Dr. Hamburg. In retrospect, clearly, I would have hoped
that there would have been greater communication. That speaks
to the issue that was raised about ensuring the appropriate
level of back and forth communication and coordination with our
State partners. When this email was received, it was in the
context of a violation of State pharmacy registration and
licensure. While there was an indication that they had sent
product in the absence of specific patient prescriptions, there
was no indication of a safety or quality concern that was being
raised.
We really felt that it was--as I understand, those kinds of
issues are often handled by the State board of pharmacy. We
should have made sure that Massachusetts was aware, and it
underscores the need for greatly enhanced communication and
coordination. The other aspect speaks to the larger question
that we really need to work on clarifying and trying to figure
out how to address this issue of compounding versus
manufacturing and when does one authority kick in and when does
the other apply.
Senator Bennet. I think Senator Alexander hit the nail on
the head. It's a question of clarity, of what the roles and
responsibilities here really are, so that what, at the best, is
bureaucratic in difference--and it's probably worse than that,
I suspect--causes this kind of thing.
Mr. Chairman, thank you for holding this hearing.
The Chairman. Thank you, Senator Bennet.
I'm starting another round. I don't know how many Senators
would like to have more questions. I just have a couple.
Dr. Hamburg, unlike NECC, where there is a lack of clarity,
as we now know, regarding the FDA's authority, there's another
company called Ameridose.
Dr. Hamburg. Yes.
The Chairman. Owned by the same people, run by the same
people, closely aligned. Ameridose is registered with the FDA.
Although it is essentially a large-scale compounder--it is a
large-scale compounder--it provides products to hundreds of
hospitals all over the country. Now, given that the two
companies are owned and run by the same people, that the FDA
inspectors documented many similar serious problems at
Ameridose and NECC, could the contamination just have easily
occurred at Ameridose?
For example, in 2008, the regional inspector for the FDA
recommended a warning letter to be issued to Ameridose, but it
never got sent. I'm wondering whether what you're recommending
is clarifying enough, that compounders like NECC are subject to
FDA's authority. Is that really enough, if FDA already had the
authority with regard to Ameridose?
Dr. Hamburg. I can't speak to the specifics of Ameridose
because it is the subject of an ongoing investigation. It
speaks to this issue of these hybrids of compounding pharmacies
that are merging more into manufacturing, and the fact that we
do need a system that is clearer.
Registration with the FDA does not necessarily mean that
they become a drug manufacturer. People register with us for
all kinds of reasons and never even are putting anything into
commerce. It means, we get their name and address. We never got
listings of products that Ameridose was manufacturing, but we
were engaged with them in terms of inspections and responding
to some specific complaints and concerns.
I really think we need to work together to figure out how
to address this evolving field of nontraditional compounding,
because it can serve an important need. We need to be able to
define it more and be able to really apply the right
enforcement approaches.
The Chairman. I got it. I got that. I just keep saying that
FDA had authority over Ameridose but didn't exercise that
authority. This was clear.
Dr. Hamburg. We were in Ameridose and took some actions
related to some specific concerns in the facility. In 2010, I
think it was, we were in there around an issue with a
particular product, nicardipine, I believe.
The Chairman. I will take a look at that. I just know that
in 2008----
Dr. Hamburg. There was a--my colleague was just reminding
me--a recall of a super potent----
The Chairman. Oh, this.
Dr. Hamburg [continuing]. Fentanyl product.
The Chairman. That's very true. One was super potent and
one was subpotent.
Dr. Hamburg. There was one that was dramatically super
potent and one that was less potent. We were in there and we
did take actions. Again, I can't speak to all the specifics
because we're still investigating, looking at that internally
as to what we should have done, and it's part of a broader
investigation.
The Chairman. OK. I got that. I'll look at Ameridose, but
it seems to me that that was a clear cut case but we still
weren't exercising authority.
I did have one more question, Dr. Smith. You know, I look
at this history, and I'm pointing it out not just to point a
finger at something and to chastise, but to understand that
certain structures don't accomplish what people think they
accomplish. In 2003, staff from the FDA met with the staff from
the Massachusetts Board of Pharmacy to discuss,
`` . . . the potential for serious public health
consequences if NECC's compounding practices, in
particular, those relating to sterile products, are not
improved.''
That was in 2003.
At that meeting, consensus was reached that primary
jurisdiction over NECC rested with the board, Massachusetts.
The board then took 1 year to get a staff investigator to
recommend censure, 6 months to actually issue a censure in the
form of a draft consent decree, another whole year to arrive at
a signed consent decree which then lasted for all of 6 months.
In all, it took the board 4 years from the time MPA-caused
meningitis was reported to make NECC hire a third party to
review and improve its sterility procedures. Again, this is not
effective oversight.
Maybe I'm making a statement more than a question. I'm
saying that sometimes we set up these structures, and we people
them with the very people that they're supposed to be policing.
In this case, I'm informed that a member of this board is a
person who actually works for Ameridose, and his or her
paycheck--I forget the gender of the person--their paycheck
comes from the very company that they're supposed to be
overseeing.
We see this happening in a lot of different States, where
boards are set up but they're peopled with the very people that
they're supposed to be policing. They're all friends. They go
to the same clubs. They belong to the same this and the same
that, and it's sort of a wink and a nod and a pat on the back.
Sometimes that's why I think that for effective oversight, you
need the expertise of people in the field, but only to inform a
board, not to actually exercise that kind of jurisdiction.
Dr. Smith. You bring up very important points. The Board of
Pharmacy in Massachusetts, by statute, indicates who is allowed
to be on the board. Certainly, in evaluating as part of this
review the function of the board, that's something that's also
going to be taken up by the special commission that we've
established to be able to really provide us with best practices
about what kind of board makeup might be better suited or
better balanced to be able to perform the oversight function
that is so crucial.
If I could just say one other thing about the lapses that
you clearly point out, I would say that the emergency
regulations that we issued on November 1st include two that I
think are very important. One would be to require pharmacies in
Massachusetts who are the subject of State or Federal
investigations to disclose that and make that known to us. That
would get at the issue that Senator Bennet raised of
Massachusetts not being aware at the time that Colorado issued
a cease and desist letter. That would be very important.
The other would be that sterile compounding pharmacies must
supply information about volume and distribution patterns to
the State board. Right now, that is not required. And, clearly,
compounding pharmacies like NECC who are acting in a de facto
manufacturing-like role would then have to tell us information
about how much they're making, what they're making, and where
they're shipping it to.
That would allow us to identify pharmacies that are doing
that kind of practice, as opposed to the neighborhood
compounder that's doing that necessary compounding or the ones
that are doing it within State law, which is one prescription
at a time. NECC was violating that as well.
The Chairman. Got it. Thank you.
Senator Roberts.
Senator Roberts. Thank you, Mr. Chairman, and thank you for
citing the timeframe that is most frustrating to this.
Doctor, you said that if there were sterility issues, you
could have shut the manufacturer down. I'm having a lot of
trouble here with this. On 4/16/2002, FDA report cited
sterility issues and lack of accountability by NECC and Mr.
Cadden as the former CEO or director, he took the Fifth over in
the House yesterday, we asked him to appear and he did not.
I might add that this timeline was prepared by our staff,
the committee staff, the chairman's staff. We asked for a
timeline from you in regards to any actions that you have taken
against any compounding manufacturer. We have yet to receive
that, and I would hope that we could get it.
But this is 2002. Mr. Chairman, we go through 2002--a
complaint, 2002 adverse event, FDA inspections, FDA 483. By the
way, the 483 is like a 1099 in regards to your taxes. You don't
want to get a 483. That says you're in trouble, and you've got
to answer. I have the answer by the New England Compounding
Center. Then I have the warning letter back.
I could go down all of the things that have happened here--
investigation, complaint, board action, board action,
inspection. We go clear down here, another whole page of it--
letter, board action, board consent, board compliance,
compliance, other licensing, advisory letters, licensing.
Finally, in 2006, a warning letter. Finally, we get something
done.
Here's the warning letter. In the warning letter--and here,
by the way, is the 483 that says you're in trouble--2002.
Finally, after all of these things happen, in 2006, we have a
warning letter. All right. What happens with a warning letter?
And then New England Compounding Centers respond, and then you
respond to them about the warning letter. So this is a warning
letter after the response to the warning letter.
And you say,
``Your firm must promptly correct the violations
noted in December 4, 2006, warning letter and establish
procedures to assure that such violations do not
reoccur. Its failure to do so will result in
enforcement action, including seizure of the firm's
products and an injunction against the firm and its
principals. In a future inspection, we will confirm the
commitments that you made in your response and verify
that your firm's compounding practices are consistent
with the policy articulated,''
et cetera, et cetera, et cetera.
That's a pretty strong response. What happened? Actually,
nothing happened until 2008, and then there was another 483.
I'm not going to go through all that. We went through that.
That involved Colorado. And, finally, we get to a 483 of
October 26, 2012, finding multiple sources of contamination and
air sampling showing contaminants 6 months prior to compounding
of MPA. This has been going on since 2002. This is amazing.
These are steroid injections, by the way, that when there
was an inspection, there were vials of the product and there
was black fungus in the vials. Who on earth would put an
injection needle into a vial with black fungus to put into
somebody's knee or shoulder or whatever? Maybe that's the
problem I have with my knees. Hell, I don't know.
I'm just saying it took all that time, Mr. Chairman, and
nobody did anything. You say that you have the ability to shut
down somebody if they have sterility issues. I have two or
three 483s here and letters back and forth from 2002 until now,
and the thing that shut the manufacturer down was 30 lives.
Holy mackerel.
Senator Alexander is precisely correct. I don't know
whether you need a State flagpole or a Federal flagpole or
something to get us off the dime here so that if somebody gets
into this kind of a problem and you feel that you have to issue
a 483, you can shut them down. Now, what am I missing here,
other than I'm over time and I made a long statement and I
didn't allow you to have a question. By the way, thank you for
wearing purple because Kansas State is rated No. 1 in the BCS
poll.
Dr. Hamburg. Obviously, it's a very long answer and we're
out of time. Just quickly, the 2002 contaminated product issues
were responded to very swiftly in terms of going in and
inspecting. We worked with the Massachusetts Board of Pharmacy.
The products, in fact, were taken off the shelves. A decision
was made, as we discussed earlier, that because this was a
compounding pharmacy, it was under the purview of the
Massachusetts Board of Pharmacy who licenses and oversees the
day-to-day operations.
They took on that responsibility of working with the
company to resolve the sterility issues, including the consent
decree in 2006, which turned out to have serious flaws, as Dr.
Smith indicated. The belief was that the company had made
progress, working with the Massachusetts Board of Pharmacy, to
address the sterility issues.
The 2006 warning letter from the FDA actually concerned a
completely different set of issues at the facility. It had to
do with three specific products where we did have very real
concerns with the practices at NECC. It didn't have to do with
sterility failures. It had to do with basically copying FDA-
approved drugs or making unapproved drugs. They were things
that were taken seriously.
As I said earlier, I wish that we had been much prompter in
the followup on that, and perhaps we should have been more
aggressive. The response to those warning letters--and had we
taken the legal action that you indicated that we were citing
authority to take, it would have been on a set of issues
involving these specific products, and it probably--maybe we
would have been successful and it would have made a difference.
Maybe we wouldn't have been.
I wasn't at the agency at the time. I know that there was a
lot of internal debate about how to proceed. That's why it was
slowed, because of the ambiguity in the law and the fact that
there was ongoing litigation and differing opinions about the
scope of our authority coming in. I think that doesn't fully
answer your question, and I think we all wish that we had done
more. It is complicated.
Senator Roberts. OK. I've gone over and it's my fault, not
your fault--3 minutes. You're just saying basically that your
statement was erroneous. You do not have the authority to shut
people down if there's a sterility issue because you don't know
whether it's State, whether it's Federal, or whether it's
specific to this product or that product, and all of the
laundry list of things that went on here with staff and
everything else. Then you have a crisis on your hands, and
that's what happened.
It's a pretty sad situation, Mr. Chairman.
Can we get your timeline?
Dr. Hamburg. We will get you the timeline. We are still
collecting information, going through documents. This did
happen at a time when many of the people involved are no longer
at the agency. We're working hard to respond to the ongoing
public health crisis, and many of the same people that we need
to pull the documents are involved in that.
We are very focused on it. We recognize the work that you
need to do. We want to work with you, and we appreciate your
patience.
The Chairman. Thank you, Senator Roberts.
Senator Blumenthal.
Senator Blumenthal. Thank you, Mr. Chairman. I'd like to
pursue, Mr. Chairman, your questions at the very outset here
about the Ameridose matter, which, for me, in many respects, is
more serious even than the NECC from a Federal enforcement
standpoint.
I have reviewed all the documents, 483s, and inspection
reports. Clearly, serious, egregious violations of basic
standards were found by your inspectors in 2008 and then again
in 2010. Now, I take it that the recommendation was made for a
warning letter to be issued. There is no evidence in the
documents submitted to this committee that any warning letter
was ever sent. Do you disagree?
Dr. Hamburg. That is my understanding.
Senator Blumenthal. There was no warning letter ever sent.
Dr. Hamburg. No.
Senator Blumenthal. Despite findings about the lack of
potency in the drugs, the lack of proper sterility standards,
the basic cleanliness, and other kinds of minimal standards in
a company that is many times the size of NECC manufacturing
hundreds of different kinds of products sent across the Nation,
no warning letter was issued. Is that correct?
Dr. Hamburg. The product was recalled, however. My
understanding is no warning letter was sent.
Senator Blumenthal. Why was no warning letter issued?
Dr. Hamburg. We are looking into that. As I said, some of
the specifics are part of an ongoing investigation internally
and more broadly.
Senator Blumenthal. There's no question in your mind, is
there--because there wasn't in any of the inspectors who did
these reports--that FDA had full and complete authority over
Ameridose?
Dr. Hamburg. As I said, it was something of a hybrid in
terms of being a repackager-pharmacy. It wasn't a drug
manufacturer, like Merck or Pfizer, but----
Senator Blumenthal. You're telling the committee it was not
a drug manufacturer?
Dr. Hamburg. It was not a drug manufacturer in the sense of
a drug manufacturer that we have the oversight of in terms of
new products that undergo product review and approval before
licensure, that are subject to all that that entails.
Senator Blumenthal. Your inspector in the jurisdiction
section of the report in 2010 said the firm currently repacks
and manufactures prescription drug products which are FDA-
regulated drug products.
Dr. Hamburg. As I said at the outset, Ameridose is actually
the subject of an ongoing investigation, and you understand
what that entails. I have been asked not to try to characterize
Ameridose at this time as we're looking into those very
questions that you're asking.
Senator Blumenthal. Let me ask you a broader question which
looks to the future rather than the past. I want to reiterate
that much of the documents and issues that have been brought to
the committee relate to a time before you took over the
position that you have now, and we're asking both you and Dr.
Smith to answer questions about institutional performance well
before your responsibility.
Looking to the future, if there is an NECC and an Ameridose
continuing to operate out there, do you know who they are? In
other words, if you had that authority today, do you know where
you would go in terms of where the problems are, the future
tragedies waiting to happen?
Dr. Hamburg. We do not know the universe of compounding
pharmacies that might fit into this category of activity
because they are not required to register.
Senator Blumenthal. Shouldn't you know?
Dr. Hamburg. I do think that we should know, and I would
like to see that as part of new legislation if we would do it.
Senator Blumenthal. You can begin that task right now,
can't you?
Dr. Hamburg. We are beginning to reach out to our
colleagues at the State level to learn more information. We are
enhancing our activities around some of the large compounding
facilities that we know about to really make sure that we have
as much information about what they're doing and how they're
doing it.
Senator Blumenthal. Let me just suggest--and I don't mean
to sound simplistic, because I know your task is resource
challenged and we haven't really discussed the resource issue.
I know it's one that is very much a challenge for the FDA at
this point.
Dr. Hamburg. Absolutely.
Senator Blumenthal. The Congress really should be meeting
its obligation to provide those resources that are necessary
for the tasks that we're all implying you should have been
carrying out.
I would suggest very respectfully that the FDA ought to
make it a priority to scrutinize the 3,000 compounding
pharmacies, the documents that are public--and most of these
documents are public right now, as we've seen from the media.
They're available to folks who want to go into the records to
find them--and where are the next tragedies going to occur; who
will cause them; what kind of standards are they failing to
meet--so that when you're provided with that authority that is
not as limited, unclear, and contested, as you say it is now,
you can swoop down on them and shut them down or at least
require that they correct the problems that exist.
Dr. Hamburg. I really appreciate your observations,
including the one on resources, because that is a huge
challenge. We have enormous responsibilities for the protection
of the public health across a huge domain of areas of activity.
I hope that I can work with you to address the crazy quilt of
regulatory oversight that we currently have, because that will
enable us to act in a much more efficient and targeted way.
I also do think that the more we can be preventive, as you
say, rather than reactive, using our authorities that are
clearly in the law to address a contaminated product--but we
don't want to have to wait until there's a contaminated
product. We want to be able to make sure that these facilities
are operating with the kind of preventive controls and
standards of quality that the American people expect and
deserve.
Senator Blumenthal. I would just suggest that you be
preventive with a capital P, and that you regard these
renegade, outlier drug manufacturers as the threat to public
health which, clearly, they are.
Dr. Hamburg. Yes.
Senator Blumenthal. Thank you, Mr. Chairman.
The Chairman. Thank you, Senator Blumenthal.
Senator Alexander.
Senator Alexander. Mr. Chairman, I'd like to ask to place
in the record statements from the Tennessee Department of
Health, the Tennessee Board of Pharmacy, the Tennessee Hospital
Association, the Tennessee Pharmacists Association, and the
Tennessee Medical Association, all of which I asked for this
hearing.
[The information referred to may be found in Additional
Material.]
Senator Alexander. As much as I would like to focus my time
on whose fault it was, I think the families of those who were
hurt in Tennessee would like me to find out how we can make
sure this doesn't happen again. I'd like to pursue the line of
questioning that Senator Blumenthal and I and others have asked
about, for lack of a better word, the flagpole theory.
As I listen to this--and the reason I haven't asked Dr.
Smith many questions is she said, and we know, that the
Massachusetts State Board of Pharmacy had the clear authority
to deal with this problem. They just were incompetent in
dealing with it. And if anybody's going to be shut down, I
think they should be shut down. That would be where I would go.
Now, as we move over to the FDA, thinking about looking
ahead, I'm not sure--listening to the FDA's confusion and
reading their record about this, I wouldn't trust the FDA more
than I would trust the Tennessee Department of Public Health to
keep our medicines safe. In fact, the evidence that we've heard
already and that we're going to hear from the second panel is
that an example of doing things well in part of this area came
because of the alliance between Vanderbilt University and the
Tennessee Department of Health.
It leads me back to this solution, Mr. Chairman, to how we
fix accountability here. I'm trying to think through different
ways we do things in the Federal Government. I'm thinking of
our nuclear program. Admiral Rickover in the 1950s set up our
nuclear submarines, and he had a very novel idea. He
interviewed every single captain, and he told them their career
depended upon whether or not there was ever an accident on the
reactors on their submarines.
Since the 1950s, there's never been a death in connection
with any activity on a nuclear submarine, and I'm pretty sure
the reason is because if there's an accident on a nuclear
submarine, that captain's career is basically over or seriously
diminished. There's clear responsibility. It's the captain's
responsibility.
I'd like to be able to come back to a testimony 6 months
from now, after we've worked together to pass a law, and hear
representatives of State boards of pharmacy say, ``This is my
responsibility, and this is what we're doing about it,'' and
hear the FDA say, ``This is our responsibility.'' I don't want
to hear this joint responsibility that ``they were supposed to
do it, and we could have done it, but nobody did it.''
Let me narrow it down a little bit. As I understand it,
Senator Blumenthal was focusing in on manufacturing, and the
estimate I have is that there are about 5,600 manufacturers of
drugs. Is that about right?
Dr. Hamburg. There are about 6,500 facilities that are
manufacturing active pharmaceutical ingredients or drugs.
Senator Alexander. You have the total responsibility for
that. Right?
Dr. Hamburg. We do provide ongoing oversight, yes.
Senator Alexander. That's your job. That's not the
Massachusetts Board of Pharmacy----
Dr. Hamburg. Yes, absolutely.
Senator Alexander. You're on the flagpole for them. And
then you've said and others have said that the compounding
actually goes on, traditional compounding, in thousands of
pharmacies across the country, and we're not talking about
that. That's under State boards of pharmacy.
What we're really talking about--and the estimates I have
may or may not be right--is that there are about 7,500
pharmacies that specialize in advanced compounding services and
about 3,000 in sterile compounding. It's somewhere within those
facilities, where State boards of pharmacy have responsibility,
and you have some responsibility. Is that right?
Dr. Hamburg. Yes. That's the area that in our proposed
framework we'd really like to focus on as needing
clarification.
Senator Alexander. Would you like to take over the
responsibility, the total responsibility, for a certain number
of those pharmacies?
Dr. Hamburg. That might well be the best outcome.
Senator Alexander. How many of those would that be? Is that
a few hundred, or is that a few thousand, or do you know?
Dr. Hamburg. We don't know, because at the present time,
many of those facilities are not reporting information to us or
are not registered with us. We need to understand--and those
numbers are not our numbers because they don't----
Senator Alexander. No, they're my numbers, and I'm not sure
they're right. I'm just trying to get a rough idea. If you
already have 6,500 manufacturers, if you were to take over
several thousand more or several hundred more, it would make a
difference. Maybe you don't have the capacity to do that.
Dr. Hamburg. It would be a real challenge. Of course, for
our other inspectional activities over drug manufacturers, we
have user fees that help to support our budget. Senator Harkin
well knows, as we just worked so hard----
Senator Alexander. Right. I'm trying to get to a point.
Would it be conceivable that there could be a system where you
have the responsibility, but you're able to delegate that
responsibility to some States that are willing to meet
standards, and your job would be more like, say, the Nuclear
Regulatory Commission? You'd go around and check and make sure
that--it wouldn't be your job to regulate--you wouldn't
regulate the facilities, but you would basically be regulating
the States who took on that function in addition to their
supervision of traditional pharmacies.
Dr. Hamburg. That would be one model, and we could----
Senator Alexander. Is that a possibility?
Dr. Hamburg. Also lay out clear Federal standards for
practice.
Senator Alexander. Could that be done in a way that made it
clear that while you were--what that might mean, for example,
in a case like this, is that you would go to Massachusetts--
you'd have the authority to go to Massachusetts and take away
their authority completely to deal with sterile manufacturing
or sterile compounding because of incompetence or failure to
meet Federal standards, under that model.
Dr. Hamburg. That would be a possible model. It's well
worth exploring all the different ways that we could improve
the system and make sure that it is fully coordinated and
provides a safety net to protect health.
Senator Alexander. Mr. Chairman, as you can tell, my
general drift here is that looking to the future, if the
definition already is not for these advanced compounding
units--if they're not already manufacturing--and Senator
Blumenthal was suggesting they may already be--if they already
are, then they're under the FDA.
If they're not, I would suggest we make it clear that
either the Federal Government or the State government through a
set of certification from the Federal Government be on the
flagpole, have the full accountability and responsibility for
doing it. If they fail to do it, they lose their opportunity to
do that. That's one model that I would suggest.
The Chairman. Thank you very much, Senator Alexander. I
would just say that as part of this ongoing effort, Senator
Enzi and I and the committee will be sending a letter to each
State board of pharmacy to learn more about their oversight
practices in this area, including just how many large-scale
sterile compounders are operating today and who they are. We
don't know. We are preparing a letter, and I hope that I can
get all of the signatures on both sides of the aisle here to
send that letter out. It's being prepared by our staffs right
now.
I will close this panel where I started with Dr. Bell. I
talked about the need for public health and the funding. We've
heard a lot about FDA and about the necessity for FDA to take
more oversight responsibility here. Again, I remind you of what
Dr. Hamburg just said. This comes down to resources.
We continually ask the Food and Drug Administration to do
more and more and more. We ask them to do more in healthcare.
We ask them to do more in food inspections, more for imports
coming from overseas, and, to a certain point, the resources
are going to have to be there. So, I hope that when
appropriations time comes around--and we're looking at funding
for both of these, both for CDC and for the FDA--that we can
meet our obligations in making sure that they're adequately
funded to carry out the responsibilities we keep asking them to
do.
Thank you all very much.
Now we'll turn to our second panel. I guess we won't turn
to our second panel. The second panel was Barry Cadden, the
manager and co-owner of the New England Compounding Center. He
declined our invitation. We decided not to issue a subpoena. He
was subpoenaed by the House committee yesterday and showed up
and continually took the Fifth Amendment. There was no reason
to go through that charade here today with him.
On our third panel, we have--and I'll ask them to come up--
David G. Miller, the executive vice president and CEO of the
International Academy of Compounding Pharmacists, an
association which represents individual pharmacists involved in
the com-
pounding industry.
Then we have Dr. Kasey Thompson, who serves as the vice
president of the Office of Policy, Planning, and Communications
at the American Society of Health-System Pharmacies, an
organization which advises its members on the responsible use
of compounded medications. Dr. Thompson has extensive knowledge
regarding the safe use of compounded drugs, as he previously
served as ASHP's director of the Center of Patient Safety and
director of the Practice Standards and Quality Divisions.
Our third witness is one who has been referenced earlier,
Dr. Marion Kainer. I will yield to my distinguished friend and
Senator from Tennessee for purposes of introducing Dr. Kainer
from Tennessee.
Senator Alexander. Thank you, Mr. Chairman.
I'd like to welcome Dr. Marion Kainer. Our previous witness
from the Centers for Disease Control mentioned her. She'll tell
more about this, and we'll talk about it at the time. An astute
clinician at Vanderbilt University, who has a partnership with
the State of Tennessee where Dr. Kainer is director of
Healthcare Associated Infections and Antimicrobial Resistance
Program, reported something suspicious to Dr. Kainer. Within a
matter of a few days, this report led to a recall of the
material that was being spread around the United States from
this New England facility, undoubtedly saving many lives and
helping many others.
It was called by the executive director of the Association
of State and Territorial Health Officials, who said this, Mr.
Chairman:
``By the time we learned this was a problem around
the country, the information from Tennessee had already
narrowed it down to what the problem was. It was a
textbook case of how to do it right.''
Dr. Kainer obtained her medical degree and master of public
health in Melbourne. She's had a distinguished career in
Australia and the United States, with over 20 years of
experience in infection control. I compliment her for her
astuteness, her leadership, and welcome her to the panel, and I
thank the chairman for inviting her.
The Chairman. Thank you, Senator Alexander.
We welcome you all. All of your statements will be made a
part of the record in their entirety. We'll proceed in reverse
order of the introductions. We'll start with Dr. Kainer.
Dr. Kainer, I'm sure I speak for all the committee. You
have our highest praise, and we thank you for your diligence--
for being on top of this immediately and for doing exactly what
needed to be done in getting it to the Center for Disease
Control. I'll just echo what Senator Alexander said. Your
timely action and professionalism undoubtedly saved many lives.
Thank you very much and please proceed. Welcome to the
committee.
STATEMENT OF MARION KAINER, M.D., MPH, FRACP, DIRECTOR,
HEALTHCARE ASSOCIATED INFECTIONS & ANTIMICROBIAL RESISTANCE
PROGRAM, TENNESSEE DEPARTMENT OF HEALTH, NASHVILLE, TN
Dr. Kainer. Thank you. On behalf of the Tennessee
Department of Health, I would like to thank Senator Alexander
for the opportunity to comment on the fungal meningitis
outbreak. I'm the director of the Healthcare Associated
Infections and Antimicrobial Resistance Program.
In Tennessee, we now report 81 cases and 13 deaths. Our
concerns and prayers for patients, families, and loved ones
affected by this preventable tragedy are ongoing. There are
many heartbreaking stories. Some have been reported in the
media. Diana Reed's death devastated her family. Her husband
has Lou Gehrig's Disease and Diana was her husband's arms,
legs, and voice and kept his accounting business going.
Fungal meningitis is extremely rare. One of our greatest
challenges was knowing just what we were dealing with as more
and more patients fell ill. Even though we were looking for
fungus, because the initial patient reported to us had been
diagnosed with fungal meningitis, none of the diagnostic tests
yielded confirmed results until October 3d, 15 days after we
initiated our investigation of the first case. My written
remarks include a detailed chronology.
I would like to direct your attention to some early lessons
learned from this outbreak. First, compounding of medications
must be performed safely. Patients and healthcare providers
should expect safe and effective medications. Compounding
pharmacies do provide a needed service. If compounded products
are unavailable to meet the unique needs of some patients,
providers may perform compounding or repackaging themselves at
the bedside and may also put patients at risk.
Second, recent investments in public health infrastructure
through cooperative agreements from the CDC have supported
building public health capacity. This capacity was critical in
identifying and responding to this outbreak, determining the
cause resulting in product recall only 8 days after initial
notification, saving lives and limiting the number of patients
exposed.
Six members of our Healthcare Associated Infections or HAI
team are funded through the Prevention and Public Health Fund
Epidemiology and Laboratory Capacity grant and the Emerging
Infections Program. In addition, the team has a CDC/CSTE
fellow. I am the only person on the HAI team not funded by the
CDC.
Our HAI team had the expertise to conduct on-site visits,
to ask the right questions, create a database, and enter and
analyze the data swiftly to determine the cause of the outbreak
and those at highest risk of getting sick. We did an analysis
to assess the potential impact if there had been a delay in the
recall from NECC by 9 days. In Tennessee alone, we estimate by
now, we would have seen an additional 59 cases and at least
five additional deaths.
To prevent healthcare associated infections, our team has
built close relationships with infection preventionists. These
relationships are built on mutual trust and have been
invaluable in promoting open communication. Surge capacity was
provided by staff funded under the Epidemiology and Laboratory
Capacity and the Public Health Emergency Preparedness grants.
These staff reviewed clinical information and helped track
down over 1,000 exposed patients. Contact by phone or in person
was made by local public health staff funded by the State of
Tennessee. Outreach included frequent telephone calls and
knocking on doors. Our nurses tracked down one patient by
contacting a tour operator in Yellowstone Park.
Third, this outbreak illustrates the tremendous importance
of inter-facility communication when patients may seek medical
services in multiple facilities for complications that arise
from treatment at another facility. It also illustrates the
critical importance of astute clinicians in alerting public
health.
In conclusion, this has been a devastating outbreak for
patients, their families and friends, healthcare providers and
clinics. In Tennessee, we still have many patients hospitalized
and suffering from complications and others who are exposed and
frightened that they may become affected.
Sustained commitment to funding from CDC for emergency
preparedness and reduction of healthcare associated infections
has supported our productive relationships with partners and
healthcare providers across the State. These preexisting
relationships allowed us to respond quickly because we trusted
each other. We all need to work together to do our best to
prevent such a tragedy from occurring again and to ensure that
we have a public health capacity to detect and rapidly respond
to any future outbreaks.
Thank you for your time and attention.
[The prepared statement of Dr. Kainer follows:]
Prepared Statement of Marion Kainer, M.D., MPH, FRACP
summary
Communication and coordination among healthcare providers and
public health in Tennessee was unusually strong thanks to major Federal
grants to the State that have supported tracking and improving rates of
hospital-acquired infections. Years of close collaboration between
public health staff in the federally funded healthcare associated
infection program and hospital-based infection preventionists in the
State resulted in relationships and mutual trust that permitted easy
collaboration during the investigation and response to this crisis.
Despite this close relationship, cracking this investigation was
difficult because of the significant technical challenges in
definitively diagnosing fungal meningitis. We had to take actions days
in advance of being able to confirm that we were definitely dealing
with a fungus. With CDC's help, we have been able to diagnose people
much more easily since the early days of the outbreak. A timeline of
the major events in this investigation is provided in the attached
written testimony.
Recent investments in public health infrastructure through
cooperative agreements from the CDC have built public health capacity
at the TDH. This capacity was invaluable in identifying and responding
to the outbreak, determining the cause resulting in product recall only
8 days after initial notification, saving lives and limiting the number
of patients administered the contaminated injections. In Tennessee, if
the recall from NECC had been delayed by 9 days, we estimate that at
this time we would have seen an additional 59 cases and at least 5
additional deaths. If treatment guidance from CDC had been delayed, the
number of deaths would be even higher. Of the 33 Tennessee patients who
sought medical care before October 3, 9 (27.3 percent) died. Of the 48
patients who sought medical care on, or after October 3, when the first
CDC treatment guidance was issued, four (8.3 percent) died.
Six members of the Healthcare Associated Infections (HAI) team are
funded through the Prevention and Public Health Fund Epidemiology and
Laboratory Capacity Cooperative agreement and the Emerging Infections
Program. In addition, the team has a CDC/Council of State and
Territorial Epidemiologists (CSTE) fellow. The only person not funded
by CDC is the director of the HAI program, Dr. Kainer. The team had the
expertise to ask the right questions, conduct on-site visits, create
relevant standardized investigation forms, create a data base, enter
and analyze the data swiftly to determine the cause of the outbreak and
those at highest risk of getting sick. Surge capacity was provided by
staff funded under the Epidemiology and Laboratory Capacity (ELC) grant
and the Public Health Emergency Preparedness (PHEP) cooperative
agreements as well as an additional CDC/CSTE fellow and an Epidemic
Intelligence Service (EIS) officer assigned to Tennessee. State-funded
public health nurses in the field were mobilized to contact hard to
reach patients, going door to door when necessary, and maintaining
regular phone and in person contact with patients for weeks.
This has been a devastating outbreak for patients, their families
and friends, healthcare providers and clinics. In Tennessee we still
have many patients hospitalized and suffering from complications and
others who are exposed and frightened that they may become infected.
Sustained commitment to funding for emergency preparedness and
reduction of healthcare associated infections through cooperative
agreements from the CDC has supported our productive relationships with
our partners and healthcare providers across the State. These pre-
existing relationships allowed us to respond quickly because we trusted
each other. We all need to work together to do our best to prevent such
a tragedy from occurring again and to ensure that we have the public
health capacity to detect and rapidly respond to any future outbreaks.
______
On behalf of the Tennessee Department of Health, I would like to
thank Senator Alexander for the opportunity to comment on the recent
fungal meningitis outbreak. I hope to provide some insights from this
tragic outbreak to the Health, Education, Labor, and Pensions (HELP)
Committee which I hope will assist the committee to gain an
understanding of potential opportunities to prevent and respond to such
devastating outbreaks in the future.
As of November 13, Tennessee reported 81 cases and 13 deaths.
Behind each one of these numbers is a lot of suffering of the patients
affected, their loved ones and the communities in which they
participated. One example: The death of Diana Reed who, according to
her brother, was her husband's arms, legs and voice, has been
devastating. Her husband has Lou Gehrig's Disease and Diana was
instrumental in keeping his accounting business going and in helping
her husband get in and out of bed, the shower and his wheelchair. The
family is trying to figure out how they will carry on and enable her
husband the ability to maintain his dignity and to keep his work
without her; they shared their story with the New York Times.
Fungal meningitis is extremely rare. One of our great challenges
was knowing just what we were dealing with as more and more patients
fell ill. Even though we were looking for a fungus because the initial
patient reported to us had been diagnosed with a fungal meningitis,
none of the diagnostic tests yielded confirmed results until October 3,
15 days after we initiated our investigation of the first case.
Below is an outline of the timeline of major events of this
outbreak and the role of the Tennessee Department of Health in this
investigation. I will also discuss lessons learned in the context of
this investigation.
Timeline of Major Events
------------------------------------------------------------------------
Case count as
Date Major events known at that time
------------------------------------------------------------------------
Day 1: Tuesday, Sept. 18........ Dr. Marion Kainer, 1 case of
Director of the Aspergillus
Tennessee meningitis
Department of
Health (TDH)
Healthcare
Associated
Infections and
Antimicrobial
Resistance
Program, receives
an email sent by
Dr. April Pettit,
Infectious
Diseases
Physician,
Vanderbilt
University
Medical Center
(VUMC) about a
patient with
meningitis caused
by a fungus,
Aspergillus
fumigatus, who
had a recent
epidural
injection at a
pain clinic.
Dr. Kainer and Dr
Pettit discuss
the case.
Dr. Kainer speaks
with Ms. Candace
Smith, infection
preventionist
(IP) at St Thomas
Hospital (STH),
which is
organizationally
affiliated with
the St Thomas
Outpatient
Neurosurgical
Center (STONC)
where the patient
received the
injection. Dr.
Kainer requests
details of the
procedure, states
that the
infection is a
sentinel event of
concern, which
deserves a
careful
investigation and
requests that Ms.
Smith commence an
inspection of the
pain clinic
(e.g., evidence
of any
construction,
water damage) and
to inquire about
any potential
additional cases.
Day 3: Thursday, Sept 20........ IP from STH 1 case of
contacts Dr. Aspergillus
Kainer and meningitis
confirms that 2 cases of
index case had an meningitis,
epidural steroid unknown cause,
injection (ESI) both seeming to
at STONC; be improving
provides details No national
of the procedure. reports of
Because the Aspergillus
facility manager meningitis
of STONC is on
vacation, the IP
at STH continues
to help in the
investigation.
Dr. Kainer
contacts Dr. Perz
at the Division
of Healthcare
Quality Promotion
(DHQP), Centers
for Disease
Control and
Prevention (CDC)
to ask whether
any cases of
Aspergillus
meningitis had
been reported to
CDC from any
other ambulatory
surgery centers
(ASC) or pain
clinics. Fungal
meningitis is
rare, but is not
required to be
reported to the
CDC. Even without
any requirement,
clinicians or
States often
contact CDC about
unusual
infections;
however, no one
had recently
contacted the
Mycotics Branch
at CDC to report
any cases of
Aspergillus
meningitis.
STH reports two
additional
patients with
meningitis with
high levels of
white blood cells
but no known
cause. Both had
undergone ESIs at
STONC. Diagnoses
were complicated
because the
patients appeared
to be getting
better and the
cause of their
meningitis was
unknown. Dr.
Kainer worked
with clinicians
to request
exhaustive
diagnostic tests.
They also had ESI
performed by same
anesthesiologist
at STONC. The
preservative-free
methylprednisolon
e acetate used in
their ESIs was
obtained from New
England
Compounding
Center (NECC).
Arrange for one on
Dr Kainer's staff
to visit STONC
the next morning,
with the IP and
the ID physician
from STH..
On this day, STONC
closes
voluntarily,
sequesters
supplies and
orders new
supplies from
other
distributors.
Day 4: Friday, Sept 21.......... Visit to STONC by 1 case of
TDH staff for a Aspergillus
careful review of meningitis
all procedures 2 cases of
and the physical meningitis of
environment: no unknown cause
evidence observed 1 case of stroke
of environmental and meningitis,
conditions that unknown cause
would have led to 1 case of stroke,
fungal no spinal tap was
contamination of done
procedures.
TDH contacts CDC
and describes
findings of site
visit. TDH asks
CDC to help with
laboratory
testing of
patients with
meningitis of
unknown cause
(because fungus
is very hard to
diagnose) and
also for testing
of environmental
samples from the
clinic, if needed.
Another patient
with meningitis
and stroke with a
history of ESI at
STONC is
identified, while
VUMC also reports
yet another
patient who had a
stroke and had an
epidural
injection, but at
the time it was
not clear where
the ESI was done
(it was confirmed
as STONC on Day
7).
TDH sent out a
Health Alert
using our TN
Health Alert
Network (THAN),
asking clinicians
to look for and
report any cases
of meningitis
following
epidural
injection to the
TDH.
At this time, the
leading suspected
causes of
meningitis were
the contrast
media and
methylprednisolon
e acetate (MPA)
from NECC because
both were used in
each patient (and
are commonly
given together
for an ESI).
Other less likely
possibilities
included local
anesthetic, local
skin preparation
and needles used
for the injection.
Day 6: Sunday, Sept 23.......... IP at STH contacts
Dr. Kainer about
one new patient
and one patient
re-admitted with
meningitis; both
had ESI at STONC.
Day 7: Monday, Sept 24.......... Facility manager 1 case Aspergillus
from STONC has meningitis
returned from 4 cases of
vacation and meningitis
provides unknown cause
additional 1 case of stroke,
information on but no spinal tap
the facility done
practices. TDH
staff arrange to
begin collecting
data on patients
to try to find
out what
distinguishes the
case patients
from those who
did not get sick.
TDH and CDC
communicating
closely.
Dr. Kainer
contacts State
epidemiologist at
Massachusetts
Department of
Health, Dr. Al
DeMaria, to
request a
conference call
with TDH, CDC, MA
staff and NECC to
obtain
distribution list
of clinics that
got MPA from NECC
in order to look
for other cases
of meningitis
among patients
who received ESI
with MPA
compounded by
NECC.
Day 8: Tuesday, Sept 25......... 2 new cases of 1 case Aspergillus
meningitis meningitis
reported to TDH. 6 cases of
Both had ESI meningitis
using MPA from unknown cause
NECC at STONC; 1 case of stroke,
however, one of but no spinal tap
the patients did done
not receive the 1 case of other
suspected neurologic
contrast and the problems and
procedure was abnormal spinal
done by a tap (unknown
different cause)
anesthesiologist.
Conference call
with TDH, CDC,
Massachusetts
Department of
Health and Board
of Registration
in Pharmacy
(MABRP) and NECC.
NECC stated no
adverse events
reported, no new
suppliers of
ingredients or
changes in
procedures. TDH
described
severity of cases
and that
preservative free
MPA was leading
hypothesis. TDH
requested
distribution list
and verified that
voluntary recall
procedures were
in place.
TDH staff begin
collecting all
the medical
information
needed to conduct
their
epidemiologic
studies.
STONC starts
contacting
potentially
exposed patients.
A new patient who
had an ESI at
STONC was
admitted to STH
with numbness and
bowel/bladder
control problems,
but no headache
or fever. Her
spinal tap shows
signs of
meningitis of
unknown cause,
but with a much
lower white blood
cell count than
the other cases
of meningitis.
Day 9: Wednesday, Sept. 26...... NECC issues
voluntary recall
for three lots of
preservative free
MPA and provides
distribution list
of consignees to
MABORP and FDA.
TDH and CDC draft
an Epi-X Alert
(national
emergency alert
system for public
health
professionals) to
report cases of
meningitis
related to
epidural
injections.
TDH continues to
followup on
patients who
received ESI at
STONC to look for
any other unusual
illnesses or
complications.
CDC helps TDH by
making available
a medical doctor
with expertise in
treating fungus
to assist TN
clinicians in
caring for
patients.
Day 10: Thursday, Sept. 27...... TDH staff complete
first round of
epidemiologic
studies;
preliminary
findings supports
that MPA is a
likely source..
TDH asks STONC to
contact all
patients who had
procedures since
July 30.
Analysis of the
NECC distribution
list shows two
other clinics in
TN received MPA.
These clinics are
contacted and all
MPA is
sequestered. Both
clinics cease
performing ESIs.
The first clear
evidence that the
meningitis cause
is not related to
the STONC clinic:
North Carolina
(NC) reports a
patient with
meningitis
exposed to MPA
from NECC.
Day 11: Friday, Sept. 28........ It is still not
absolutely clear
that the MPA from
NECC is the only
possible source
of contamination:
the NC case
patient had also
received
lidocaine and
povidone iodine
from the same
manufacturers
used by STONC.
The lidocaine was
the same lot
number.
CDC notifies all
State Health
Departments of
situation and
urges them to
contact clinics
who do ESIs to
ask them to
contact and check
on the health of
recipients of MPA
using a script
prepared by CDC.
They ask that
this be done
immediately, not
waiting until
after the weekend.
CDC issues another
national Epi-X
alert indicating
that this now is
a multistate
outbreak and
requesting
reports of
meningitis, other
neurological
infections, and
stroke. TDH sends
its own alert
through THAN to
clinicians and
hospitals in TN
to look for and
report
meningitis,
stroke and focal
infections in
patients who have
had epidural
injections.
Still, all
diagnostic tests
on these cases
remain negative.
The only patient
with a confirmed
diagnosis remains
the first case
patient reported.
This highlights
the difficulty of
diagnosing a
fungal infection,
even when one is
looking very hard
to find it.
TDH continues to
work on
epidemiologic
studies to learn
more about these
patients, despite
not yet having a
confirmed
diagnosis. TDH
requests
assistance from
CDC to abstract
clinical data
from patient
records (help
arrives on Day
14).
Day 13: Sunday, Sept 30......... TDH and STONC
staff continue to
abstract data on
patients who had
procedures since
July 1.
Day 14: Monday, Oct 1........... TDH holds its 11 cases, 2 deaths
first press
conference and
initiates a daily
scheduled press
briefing.
TDH partners with
the State Poison
Control Center to
assist in
responding to
questions from
the general
public.
Other TN clinics
continue to
contact patients
exposed to MPA
from NECC. CDC
and TDH staff
work on gathering
patient data to
continue studies.
TDH participates
on call with
expert fungal
clinical panel
convened by CDC,
discuss need for
CDC to provide
interim
suggestions/
advice to
clinicians on
diagnosis and
treatment.
Day 15: Wednesday, Oct 3........ CDC issues interim 18 cases, 2 deaths
guidance on
diagnostics and
clinical
management using
input from an
expert fungal
clinical panel
convened by CDC.
For the first time
since the initial
report, a tissue
biopsy from a
case patient
shows a fungus.
However, the
fungus looks
different than
Aspergillus. More
tests must be
done to identify
it.
TDH issues another
alert through
THAN to
clinicians to
help them
identify,
diagnose and
treat ill persons
exposed to MPA
from NECC.
TDH analysis of
STONC patients
suggests that one
particular lot of
the three NECC
MPA lots present
at STONC is the
most likely to
make patients
sick: Lot
06292012.
Day 16: Thursday, Oct 4......... A final
identification of
the fungus
causing illness
is still not
made, but a
specimen from
another patient
who died shows a
fungus that is
not Aspergillus.
FDA announces
fungus was seen
on microscopic
examination of an
unopened vial of
MPA from Lot
08102012. This
now is very
strong evidence
that MPA is the
cause of the
outbreak.
TDH alerts TN
healthcare
facilities using
THAN to cease use
of all
medications and
products from
NECC.
Day 17: Friday, Oct 5........... TDH opens State 29 cases, 3 deaths
health operations
center to assist
in case tracking,
active
surveillance
(contacting,
reaching out to
all persons who
received MPA from
NECC at any of
the three
Tennessee
clinics--a total
of 1,009
persons).
Mobilize regional
health operations
centers and use
public health
nurses to contact
hard to reach
patients, going
door to door when
necessary. Public
health nurses
maintained
regular phone and
in person contact
with affected
patients for
weeks, changing
messaging as
required to
adjust to a fluid
and constantly
changing
scientific
understanding and
related patient
needs.
The CDC has
another meeting
of its expert
fungal panel.
Day 18: Saturday, Oct 6......... NECC announces 29 cases, 3 deaths
voluntary recall
of all NECC
products.
FDA issues
Medwatch alert
asking providers
to stop using any
NECC products.
Day 24: Friday, Oct 12.......... MMWR (CDC 50 cases, 6 deaths
publication) is
published on
clinical
presentation of
cases.
Day 26: Sunday, Oct 14.......... FDA call with 53 cases, 6 deaths
States and CDC on
concerns about
sterility of any
product from NECC.
Day 27: Monday, Oct 15.......... FDA issues 53 cases, 6 deaths
Medwatch alert.
TDH works with the
Tennessee
Hospital
Association
(THA), the TN
medical
association
(TMA), the
ambulatory
surgery center
association and
the TN pharmacist
association to
assist in
alerting
hospitals,
providers and
clinics to
identify and
notify patients
who received NECC
products.
Day 29: Wednesday, Oct 17....... TDH identifies 61 cases, 8 deaths
that patients who
received older
vials are much
more likely to
get sick.
Questions begin
about whether or
not to test these
patients even if
they are not
sick, if testing
might prevent
serious illness
such as stroke.
Day 30: Thursday, Oct 18........ TDH works with CDC 63 cases, 8 deaths
experts to
develop a
mathematical
model used for
decision analysis
by CDC about what
to do for high
risk patients.
For the first
time, CDC and FDA
confirm presence
of Exserohilum
rostratum in
unopened vials
from Lot
0810210@51.
This is now
definitive
evidence that
contaminated MPA
is the cause of
the outbreak.
Day 35: Tuesday, Oct 23......... MA Board of 70 cases, 9 deaths
Registration in
Pharmacy issues
report of initial
preliminary
findings.
Day 38: Friday, Oct 26.......... FDA releases copy 74 cases, 10
of FDA form 483. deaths
All 50 vials of
MPA tested showed
contamination
(likely fungal).
Day 48: Tuesday, Nov 6.......... The New England 78 cases, 13
Journal of deaths
Medicine
publishes an
article written
by TDH and CDC
investigators on
this outbreak:
http://
www.nejm.org/doi/
full/10.1056/
NEJMoa1212972 .
Day 51: Friday, Nov 9........... TDH invited to 81 cases, 13
provide testimony deaths
to the Senate
HELP committee.
TDH requests on-
site assistance
again from CDC to
describe later
complications of
fungal infection,
such as epidural
abscess,
arachnoiditis and
risk factors. Two
EIS officers will
arrive on-site on
Nov 13.
------------------------------------------------------------------------
lessons learned
1. Compounding and/or repackaging of medications must be performed
safely. Patients and healthcare providers should expect safe and
effective medications. Compounding pharmacies provide a needed service.
If compounded products are unavailable to meet the unique needs of some
patients, providers may perform compounding or repackaging themselves
at the bedside and may also put patients at risk.
2. Recent investments in public health infrastructure through
cooperative agreements from the CDC have supported building public
health capacity at the TDH. This capacity was invaluable in identifying
and responding to the outbreak, determining the cause resulting in
product recall only 8 days after initial notification saving lives and
limiting the number of patients administered the contaminated
injections. Specific examples are provided below:
a. Six members of the Healthcare Associated Infections (HAI)
team are funded through the Prevention and Public Health Fund
Epidemiology and Laboratory Capacity Cooperative agreement and
the Emerging Infections Program. In addition, the team has a
CDC/Council of State and Territorial Epidemiologists (CSTE)
fellow. The only person not funded by CDC is the director of
the HAI program, Dr. Kainer.
i. The team had the expertise to ask the right
questions, conduct on-site visits, create relevant
standardized investigation forms, create a database,
enter and analyze the data swiftly to determine the
cause of the outbreak and those at highest risk of
getting sick.
ii. In Tennessee, if the recall had been delayed by 9
days, we estimate that at this time we would have seen
an additional 59 cases and at least 5 additional
deaths. If treatment guidance from CDC had been
delayed, the number of deaths would be even higher.
iii. To prevent healthcare associated infections, the
team has built very close relationships with infection
preventionists at hospitals, the Tennessee Hospital
Association and is building relationships with the
ambulatory surgery center community. These
relationships are built on mutual trust and have been
invaluable in promoting open communication.
b. Surge capacity was provided by staff funded under the
Epidemiology and Laboratory Capacity (ELC) grant and the Public
Health Emergency Preparedness (PHEP) cooperative agreements as
well as an additional CDC/CSTE fellow and an Epidemic
Intelligence Service (EIS) officer assigned to Tennessee.
i. These staff-funded provided assistance in
reviewing clinical information on suspect and confirmed
cases, and in tracking down 1,009 exposed patients.
Contact by phone or in person was made by local public
health department staff, funded by the State of
Tennessee, sometimes with assistance from law
enforcement. Outreach included frequent telephone calls
and door to door tracking, including home visits
whenever necessary. Some exposed patients were living
in or traveling in other States or were overseas when
they developed symptoms.
ii. The State Health Operations Center provided the
necessary infrastructure to coordinate activities among
the 170 public health staff in Tennessee.
iii. The alert network (THAN) connecting TDH with
clinicians and staff at hospitals was invaluable in
rapidly getting information out.
iv. We were able to use a database designed for
tracking persons in shelters to track patients who were
exposed.
3. Relationships with Federal partners were critical in the
response to this outbreak.
a. CDC provided invaluable assistance throughout the outbreak
including weeknights and weekends. Some examples include:
i. Laboratory support: CDC developed a diagnostic
test to assist in the outbreak investigation and
provided laboratory support for confirming the
identities of fungal isolates. The infectious diseases
pathology branch has been providing valuable insights
on how this fungus behaves and the type of damage it
does to tissues. This has greatly assisted the
clinicians on the fungal expert working group.
ii. Clinical support: TDH was fortunate to have CDC
Epidemic Intelligence Service Officers on-site to
assist in clinical data abstraction. CDC regularly
convenes the expert fungal panel to develop diagnostic
and management guidance that has been constantly
updated with the latest clinical information. This has
been very helpful to clinicians, many of whom have
never treated fungal meningitis before, and this
guidance without a doubt saved a lot of lives. Of the
33 Tennessee patients who sought medical care before
October 3, 9 (27.3 percent) died. Of the 48 patients
who sought medical care on, or after October 3, when
the first CDC treatment guidance was issued, four (8.3
percent) died.
iii. Communications: CDC has provided relevant, up-
to-date information on case counts, diagnostic and
treatment guidance, case definitions, etc, . . . on
their Web site, through EPI-X alerts and the Health
Alert Network. They have hosted regular conference
calls with State partners and other Federal partners to
ensure accurate dissemination of information.
iv. Epidemiologic support: CDC has provided technical
support (e.g., reviewing logistic regression models,
running survival analyses) as well as coordinated the
aggregation of data across multiple States to provide a
complete national picture. Examples of critical
information include distribution of incubation periods.
CDC provided expertise in mathematical modeling to
review whether guidance needed to be changed for
asymptomatic patients at high risk of infection in
order to prevent strokes or death.
v. Coordination: CDC has coordinated the national
response with other States and the FDA.
vi. Funding through cooperative agreements--please
see above note #2 on how these funds were used to build
capacity at the TDH.
b. FDA provided valuable information on local inspection
findings, as well as laboratory testing of products
i. The information provided by FDA was extremely
helpful. It also would have been helpful if FDA had
shared interim findings with TDH and other State health
departments to allow them a better understanding of the
extent of the problem at the compounding pharmacy. This
type of information is very helpful as State health
departments attempt to gauge the level of risk and
consider surveillance strategies.
4. Relationships and Infrastructure
a. By focusing on emergency preparedness and on reducing
healthcare associated infections, we have made much progress in
enabling rapid communication between public health and
hospitals; however challenges remain, especially with providers
who do not work in hospitals (e.g., ambulatory surgery centers)
and with medical specialists who are not traditional emergency
response partners.
b. Use of electronic health records allowed tremendous savings
in time in allowing us to monitor the clinical progress of
patients and saved time and resources at the affected
hospitals.
c. This outbreak illustrated the tremendous importance of
inter-facility communication when patients may seek medical
services in multiple facilities for complications that arise
from treatment at another facility. Reporting to public health
is critical, as Dr. Pettit's email illustrated.
d. Communication with exposed patients during periods of great
uncertainty was very important. Public health played a vital
role in finding exposed patients that were difficult to reach
and when clinic staff were overwhelmed with the task at hand.
e. Communication with media: Frequent press-briefings allowed
TDH to effectively communicate important public health messages
in a dynamic and rapidly evolving outbreak while allowing staff
to continue to do critical work.
conclusion
This has been a devastating outbreak for patients, their families
and friends, healthcare providers and clinics. In Tennessee we still
have many patients hospitalized and suffering from complications and
others who are exposed and frightened that they may become infected.
Sustained commitment to funding for emergency preparedness and
reduction of healthcare associated infections through cooperative
agreements from the CDC has supported our productive relationships with
our partners and healthcare providers across the State. These pre-
existing relationships allowed us to respond quickly because we trusted
each other. We all need to work together to do our best to prevent such
a tragedy from occurring again and to ensure that we have the public
health capacity to detect and rapidly respond to any future outbreaks.
Thank you for your time and attention.
The Chairman. Thank you, Dr. Kainer.
Now we'll turn to you, Mr. Miller, for your statement.
STATEMENT OF DAVID G. MILLER, R.Ph., EXECUTIVE VICE PRESIDENT
AND CEO, INTERNATIONAL ACADEMY OF COM-
POUNDING PHARMACISTS, MISSOURI CITY, TX
Mr. Miller. Thank you, Chairman Harkin. I also thank the
members of the committee. My name is David Miller. I am the
executive vice president and I am proud to serve also as the
CEO of the International Academy of Compounding Pharmacists.
We are a professional association that represents
pharmacists in a wide variety of practices, local community
pharmacies, hospitals, nursing homes, hospice centers. Each one
of those pharmacists and the pharmacy technicians and the
student pharmacists that belong to our organization actually
specialize in the development of customized medication
solutions that patients need in order to meet their particular
health needs.
The tragedy of New England Compounding Center, NECC, is
quite simple to us as an organization. They were a pharmacy
that was essentially hiding behind that license and, in
reality, acting as an illegal drug manufacturer. Plain and
simple, what NECC did was to violate the trust that every
member of the public has, specifically, in their local
pharmacist, but even more so tainted the reputation of
pharmacists in every practice setting throughout the country
and placed their trust in jeopardy.
We know that NECC now acted with impunity. They failed to
adhere to the quality standards that our organization, our
profession, and our government require of us at both the State
and Federal level. We know also that NECC ignored State laws
and Federal laws as they manufactured illegally and distributed
bulk quantities of prescription drugs throughout the country.
We know what NECC did. We do not yet know fully the extent
of what allowed them to do that. It is clear that the State
Board of Pharmacy of Massachusetts failed to do their job. They
failed to protect the citizens of Massachusetts and, most
importantly, because other States relied upon their action,
their inspections, and their follow-through, permitted NECC to
continue its illegal activities and distribute tainted
medications into States throughout the United States.
More importantly, we also know that the FDA knew, as we
heard on the previous panel, of the problems with NECC. One of
the things that we find particularly appalling, not only as a
profession but, specifically, a professional association, is
that there is no question whether or not the Food and Drug
Administration had regulatory authority over this particular
business. They were engaged in illegal manufacturing of drugs.
The FDA is empowered through the FDCA and this Congress to stop
illegal manufacturing.
I have heard for 2 days and have seen a map that actually
was created by IACP being referred to by the agency as a crazy
quilt. There are questionable overlaps in the regulation of
compounding pharmacy. Let me reiterate that there is no
question who has the authority to immediately shut down an
illegal prescription drug manufacturer. That rests with the
FDA.
That is something that we find particularly disturbing,
that the agency, who knew that NECC was distributing drugs
without patient-specific prescriptions throughout the United
States, did nothing to stop them.
Last, one of the things that we have to ask ourselves as a
healthcare system is what prompted clinicians, hospitals,
facilities throughout the United States to obtain medications
from a pharmacy. We know in this particular case of
methylprednisolone acetate, the medication at issue, and others
that NECC produced was a product that was manufactured and
available in the marketplace.
What prompted, what allowed, and what permitted physicians,
hospitals, et cetera, to purchase from an illegal manufacturer?
As one of the members from the State of Tennessee asked me when
this first issue came to light, why did a hospital in Tennessee
buy medicine from a pharmacy outside of Boston? Why did they
not turn to a local accredited sterile compounding pharmacy?
Why did they do that?
That's a question, Mr. Chairman and members of the
committee, we don't yet know. There's much we don't know. What
I can tell you is this, as an organization representing and
comprised of pharmacists and pharmacy technicians, we are
absolutely committed to making sure this never happens again.
No compounding pharmacist should be able to hide behind their
license as a pharmacy or a pharmacist when, in reality, their
actions are illegal drug manufacturing. We have to stop that.
I thank the committee, and I look forward to working with
you as we attempt to solve this problem as expeditiously as
possible.
Thank you, sir.
[The prepared statement of Mr. Miller follows:]
Prepared Statement of David G. Miller, R.Ph.
summary*
IACP Vice President of Government Affairs Sarah Dodge said,
``IACP appreciates the opportunity to provide input as the
U.S. Senate HELP Committee seeks to better understand current
Federal and State oversight of pharmacy compounding and explore
the possibilities for a legislative solution to the tragedy
surrounding New England Compounding Center (NECC) business
practices.''
---------------------------------------------------------------------------
* The Summary was provided by the International Academy of
Compounding Pharmacists, of which, David G. Miller, R.Ph., is Executive
Vice President and CEO.
---------------------------------------------------------------------------
``We believe we share similar goals: an understanding of how
this tragedy happened, what can be done to prevent it from ever
happening again, and ultimately how do we assure that
compounding pharmacists are able to practice their professional
expertise without overly burdensome regulations which inhibit
quality patient care.''
The State and Federal regulatory scheme for pharmacy compounding is
complex--IACP members have valuable experience and technical
understanding of the laws that govern our industry. IACP stands ready
to help legislators and regulators to assist in conducting a thorough
and complete assessment of State and Federal laws governing the
practice of pharmacy. We believe this assessment must also examine how
regulators exercise their jurisdiction and discretion in enforcement.
IACP strongly believes that, in Massachusetts as well as other States,
many laws and regulations exist that--if they had been followed and
compliance had been enforced--would have severely mitigated the
potential for the tragic meningitis infections and the needless deaths
that have occurred.
The apparent and tragic results of NECC's alleged behavior
undermine the fundamental principal of pharmacists' practice--preserve
patient health by doing no harm. We are determined to help find the
gaps in the practice, regulatory, and enforcement system which
permitted this problem to happen and produce real solutions to prevent
it from occurring in the future. Our profession stands ready to work
with leaders from across the Federal and State governments to make sure
that what happened at NECC never happens again.
Not only does Massachusetts have State sterility requirements and
United States Pharmacopeia (USP) Standard compliance requirements, but
it retains the right to pull a pharmacy's license, if that pharmacy is
practicing outside the scope of its licensing requirements.
By all current indications, the operations of NECC were clearly
outside of the scope of their own and other States' licensure
requirements and their license should have been pulled long ago. The
Massachusetts Board of Pharmacy had the authority to do so. The FDA
also had the authority to do so once they identified NECC as engaging
in the illegal manufacturing and distribution of a prescription drug.
At a minimum, knowing what they did, both the State and the FDA
should have worked together to force the pharmacy to register as a
manufacturer and to comply with Current Good Manufacturing Practice
Guidelines (cGMP). Unfortunately, NECC showed a blatant disregard for
existing rules and regulations (no matter what the law was or might
have been, their behavior suggests that they would not have followed
it).
Additionally, and still to be answered by both regulatory agencies,
is this fundamental question: If both the State and the FDA knew of
problems at NECC--and we know that they did, based on publicly
disclosed documents--why did they fail to followup or take action? New
regulations or new laws are meaningless if the regulatory agencies
charged with upholding them simply turn a blind eye to problems and
fail to do their job.
IACP supports the following State actions, at a minimum, to help
mitigate further problems with sterility and other potential patient
hazards:
All Boards of Pharmacy must be adequately funded by State
legislatures in a manner sufficient to hire trained/educated
pharmacists to conduct regular inspections of all pharmacies. Too many
Boards have been ``de-funded'' by legislatures that have funneled
revenue from the Boards into the States' general funds leaving
administrative gaps;
Board inspectors conducting compounding pharmacy
inspections in both community and institution settings must receive
training in both the State regulations pertaining to compounding as
well as the practice itself;
All States must adopt mandatory compliance with USP <795>
and <797> standards. Only 17 currently mandate that in their laws. All
pharmacies providing compounding services--regardless of practice
setting--must be held accountable to those standards;
State Boards must ``police'' themselves and provide the
necessary assurances to other State Boards which depend upon them for
conducting inspections for non-resident pharmacies in a regular and
consistent manner. Massachusetts's Board obviously failed to execute
its responsibilities both to its citizens as well as patients in other
States in which NECC was licensed by not conducting regular
inspections.
IACP looks forward to the opportunity to testify before the Senate
HELP Committee on November 15, 2012 to further address these critical
issues.
______
The International Academy of Compounding Pharmacists (IACP)
appreciates the opportunity to provide input to the Senate HELP
Committee as the committee and legislators seek to better understand
current Federal and State oversight of pharmacy compounding and explore
the possibilities for a legislative solution to the tragedy surrounding
New England Compounding Center (NECC) business practices.
IACP is an international, professional association established in
1991 to protect, promote and advance the art and science of pharmacy
compounding. IACP provides support to more than 2,700 members through
programs and services including reimbursement/third-party advocacy,
government representation, regulatory analysis, public relations
support, referral services and a fellowship program. IACP also
represents more than 164,000 patient and practitioner advocates as part
of our P2C2 grassroots network.
IACP members are individuals; IACP does not represent or advocate
on behalf of specific pharmacies, businesses or companies. Compounding
pharmacists work directly with prescribers including physicians, nurse
practitioners and veterinarians to create customized medication
solutions for patients and animals whose health care needs cannot be
met by standardized medications manufactured by the pharmaceutical
industry.
IACP believes we share similar goals: an understanding of how this
tragedy could happen, and how to ensure the safest possible practice of
compounding in the future.
The State and Federal regulatory scheme for pharmacy compounding is
complex--IACP members have valuable experience and technical
understanding of the laws that govern our industry. IACP stands ready
to help legislators and regulators to assist you in conducting a
thorough and complete assessment of State and Federal laws governing
the practice of pharmacy. We believe this assessment should also
examine how regulators exercise their jurisdiction and discretion in
enforcement.
The apparent and tragic results of NECC's alleged behavior
undermine the fundamentals of pharmacy, which include doing no harm. We
are determined to help find the problem and solve it. Our profession
stands ready to work with you and leaders from across the Federal and
State governments to make sure that what happened at NECC never happens
again.
IACP strongly believes that, in Massachusetts and other States,
laws and regulations currently exist that--if they had been followed
and compliance had been enforced--would have severely mitigated the
potential for the tragic meningitis infections that have occurred. Not
only does Massachusetts have State sterility requirements and United
States Pharmacopeia (USP) Standard compliance requirements, but it
retains the right to pull a pharmacy's license, if that pharmacy is
practicing outside the scope of its licensing requirements.
By all current indications, the operations of NECC were clearly
outside of the scope of the State's licensure requirements and their
license should have been pulled long ago. The State and the FDA should
have worked together to force the pharmacy to register as a
manufacturer, but also to comply with Current Good Manufacturing
Practice Guidelines (CGMP). Unfortunately, NECC showed a blatant
disregard for existing rules and regulations (no matter what the law
was, their behavior indicates that they would not have followed it).
Millions of Americans have unique health needs that off-the-shelf
prescription medicines cannot meet. For them, customized medicines--
prescribed or ordered by licensed prescribers and mixed safely by
trained, licensed compounding pharmacists--are the only way to better
health.
By definition, compounded medicines are different than commercial
pharmaceuticals; they are prepared at the direction of licensed
prescribers to meet patients' individual needs that are not met by
manufactured pharmaceuticals. As a result, Federal requirements
designed for large-scale manufacture of uniformly dosed drugs do not
apply to compounding pharmacies.
Many patients depend on compounded medicines, including children,
those with allergies, cancer patients, children with autism, senior
citizens, menopausal women, hospice patients and those who rely upon
discontinued drugs. For patients who are unable to take medications
orally or as injections--the traditional dosage forms for manufactured
drugs--compounding pharmacists can create alternate methods of
delivery, like ointments, solutions or suppositories, to fit their
unique health needs.
Many, if not most, of the lifesaving intravenous drugs given in
hospitals and clinics are compounded. Because hospital patients are
often on multiple medications, compounding them into one treatment
saves the hospital personnel time and the patient multiple injections
or administrations.
Additionally, compounded medications are often used by
veterinarians and pet owners for the care of their pets. Animals come
in all shapes and sizes, so one-size-fits-all pharmaceuticals do not
always meet their needs. In many cases, a compounded medication may be
necessary for a non-food animal to be satisfactorily treated.
In 2003, IACP established a 501(c)(3) foundation to further
research and educational initiatives for the advancement of pharmacy
compounding. Its mission is to conduct and publish research studies,
establish academic alliances, and institute educational programs and
issue forums.
In 2004, IACP joined a coalition of eight leading pharmacy
professional and regulatory organizations in the creation of a
voluntary accreditation program for pharmacy compounding. The Pharmacy
Compounding Accreditation Board (PCAB) helps to assure quality and
raise awareness of the profession.
To begin with, IACP would support the following State actions to
help mitigate further problems with sterility and other potential
patient hazards:
All Boards of Pharmacy must be adequately funded by State
legislatures in a manner sufficient to hire trained/educated
pharmacists to conduct regular inspections of all pharmacies. Too many
Boards have been ``de-funded'' by legislatures that have funneled
revenue from the Boards into the States' general funds leaving
administrative gaps;
Board inspectors conducting compounding pharmacy
inspections in both community and institutional settings must receive
training in both the State regulations pertaining to compounding as
well as the practice itself;
All States must adopt mandatory compliance with USP <795>
AND <797> standards. Only 17 currently have that on their books; and
State Boards must ``police'' themselves and provide the necessary
assurances to other State Boards which depend upon them for conducting
inspections for non-resident pharmacies in a regular and consistent
manner.
Massachusetts's Board obviously failed to execute its
responsibilities both to its citizens as well as patients in other
States in which NECC was licensed by not conducting regular
inspections.
Many States address specific compounding standards either through
existing State laws and regulations and/or through the State's adoption
of USP standards for compounding pharmacy practices. IACP has submitted
this information to the committee as part of its responses to committee
questions issued to stakeholders prior to this hearing.
Uncertainty about the application of section 503A does not affect
oversight of pharmacy compounding. As mentioned, the States do address
compounding, specifically, and provide appropriate governing
compounding standards. Moreover, some States already (and all should)
require mandatory compliance with USP <795> AND <797> standards. To
reiterate, IACP supports adoption of mandatory compliance with USP 795/
595 by all States.
From the Federal standpoint, the FDCA's existing inspection
provision, section 704, allows FDA oversight when a pharmacy is not
operating in conformity with governing State laws, or akin to a drug
manufacturer. FDCA section 704 contains two very important components:
1. Pursuant to the first sentence of section 704(a), FDA is
permitted to inspect ``all pertinent equipment, finished and unfinished
materials, containers, and labeling therein'' of any pharmacy. FDA can
glean the information it needs to determine whether a pharmacy is
engaged in manufacturing through its inspection of these items.
2. FDA gains enhanced inspection authority to inspect a pharmacy
that is operating as if it were a manufacturer. This authority exists
whenever a pharmacy:
(a) is not operating in conformity with State laws regulating the
practice of pharmacy;
(b) is not regularly engaged in dispensing prescription drugs upon
the prescriptions of licensed practitioners; and
(c) is compounding drugs for sale other than in the regular course
of its business at retail. See section 704(a)(2)(A).
Notably, the enhanced authority granted to FDA under these
circumstances is the same inspection authority FDA possesses with
regard to drug manufacturers. Thus, existing FDCA section 704 allows
FDA to inspect a noncompliant pharmacy such as NECC as a manufacturer,
subjecting it to inspection for ``all things therein (including
records, files, papers, processes, controls, and facilities) bearing on
whether prescription drugs . . . which are adulterated or misbranded
within the meaning of [the FDCA] . . . have been or are being
manufactured, processed, packed, transported, or held in any such
place, or otherwise bearing on violation of [the FDCA]. (Section 704(a)
(sentence three).
IACP strongly believes that the States have laws and regulations in
place that regulate the professional practice of pharmacy, and they
have for hundreds of years. State laws, for example, govern
anticipatory compounding (appropriately based on a history between the
pharmacy and the physician or patient to ensure adequate supply) and
beyond-use dates for drugs, both of which necessarily limit how much of
a drug may be compounded in advance.
Anticipatory compounding is also a required component of most
States' laws to ensure timely patient access to drugs and thereby
prevent wait-time and/or unavailability that may be harmful to the
patient's health. States similarly regulate such things as standards
for active pharmaceutical ingredients (APIs) used in compounding;
ability to compound commercial copies; and percentage of compounded
preparations that may be shipped out of State, i.e., many of the things
existing section 503A simply attempts to reiterate.
Notably, when a pharmacy operates outside the scope of its State
laws and regulations governing the professional practice of pharmacy,
that pharmacy subjects itself to FDA inspection and oversight, and full
FDCA application to the same extent as a drug manufacturer. NECC serves
as a prime example of a pharmacy that both breached State pharmacy
regulatory laws and that should have been held accountable as a
manufacturer by FDA. Such a non-State law compliant pharmacy no longer
operates within the professional practice of pharmacy, which has always
been effectively and traditionally regulated by the States through
statutes and regulations developed over the course of more than a
century.
IACP believes that, since the practice of pharmacy (much like the
practice of medicine, veterinary medicine, nursing, etc.) is already
regulated at the State level, the majority of policy and oversight is
best if implemented/addressed/enforced at the licensure level. States
have the ability to remove a pharmacy's license if that pharmacy is not
operating within its licensure requirements.
States also already have in place levels of licensure, depending on
the function and scope of practice. The Federal Government has clear
oversight and jurisdiction if that pharmacy is acting as a
manufacturer. Should a pharmacy be acting in a manufacturing fashion,
they should be licensed as a manufacturer and subject to CGMP, as are
all other manufacturers.
Again, IACP believes that all States must adopt mandatory
compliance with USP <795> AND <797> standards. Only 17 States currently
have adopted USP standards.
With regard to ``manufacturing,'' IACP has long maintained and
continues to maintain, that volume, percentage of sales, use of
``commercial'' equipment, or interstate sales should not be the
determining factor in what constitutes a manufacturing practice. A
pharmacy that focuses much of its practice upon compounding gains even
greater experience with the activity, and thus has heightened expertise
and experience that benefit, rather than harm, recipient patients. By
analogy, an experienced heart surgeon is far more preferable than a
surgeon who performs heart surgery only sporadically. IACP thus
believes that rather than indicators such as volume, percentage of
sales, interstate shipment, etc., it is the activity of the pharmacy
with regard to what they do with medicines they dispense that must be
scrutinized to determine whether or not they are engaged in
manufacturing.
IACP strongly believes that the current statutory definition of
manufacturing (as it reads in the Controlled Substances Act) (CSA)
sufficiently defines, and distinguishes manufacturing from the practice
of pharmacy compounding (see citation) Notably, the CSA definition
dovetails nicely with existing FDCA section 704, as described above.
Both hinge on the status of ``pharmacy'' or, conversely,
``manufacturer,'' of whether the company preparing the drug operates in
conformity with applicable State laws governing the practice of
pharmacy and as an incident to dispensing such drug in the course of
professional pharmacy practice.
Should Congress believe it is appropriate, it may be helpful to
reiterate (mirror) the CSA definition in the Federal Food, Drug and
Cosmetic Act (FDCA) as an appropriate standard for distinguishing
between drug manufacturing and the medical practice of pharmacy
compounding. Such inclusion also promotes uniformity between the two
Federal acts. The CSA, (21 U.S.C. Sec. 802 (112-90) TITLE 21--FOOD AND
DRUGS, SUBCHAPTER I--CONTROL AND ENFORCEMENT Part A (15) states:
``(15) The term ``manufacture'' means the production,
preparation, propagation, compounding, or processing of a drug
or other substance, either directly or indirectly or by
extraction from substances of natural origin, or independently
by means of chemical synthesis or by a combination of
extraction and chemical synthesis, and includes any packaging
or repackaging of such substance or labeling or relabeling of
its container; except that such term does not include the
preparation, compounding, packaging, or labeling of a drug or
other substance in conformity with applicable State or local
law by a practitioner as an incident to his administration or
dispensing of such drug or substance in the course of his
professional practice. The term ``manufacturer'' means a person
who manufactures a drug or other substance.''
Additionally, the CSA States the following in terms of
differentiating between interstate and intrastate commerce (21 USC Sec.
801 (112-90), TITLE 21--FOOD AND DRUGS. SUBCHAPTER I--CONTROL AND
ENFORCEMENT Part A (5):
``(5) Controlled substances manufactured and distributed
intrastate cannot be differentiated from controlled substances
manufactured and distributed interstate. Thus, it is not
feasible to distinguish, in terms of controls, between
controlled substances manufactured and distributed interstate
and controlled substances manufactured and distributed
intrastate.''
Any changes to the statutory definitions of ``manufacture'' in
either the CSA or the FDCA, or any changes to related regulations and/
or agency policies, should be consistent as they apply to compounding
pharmacies. For example, under either the FDCA or the CSA, a pharmacist
should, with a prescription from a licensed physician, be able to
compound patient-specific medications, controlled substance or not,
sterile or unsterile, and deliver them directly to the prescribing
physician for office administration when medically necessary as
determined by the physician.
This alone should not trigger a requirement that the pharmacist
register with either the DEA or the FDA as a ``manufacturer.'' However,
under current DEA policy, based on the agency's interpretation of the
CSA, unless the drug (controlled substance) is delivered directly to
the ``end user,'' (i.e. the patient), registration as a
``manufacturer'' is required, even when the pharmacist is compounding
the drug pursuant to a valid prescription and delivering the drug to
the prescribing physician for medically necessary office
administration.
This is a particularly troubling policy by the DEA as it relates to
sterile, injectable compounds, which often must be surgically implanted
and delivered via intrathecal pain pump. As the recent tragedy
involving the NECC has shown, maintaining sterility throughout the
compounding process and the administration of injectable compounded
drugs is critical to patient safety.
DEA's current policy runs counter to both their stated goal of
preventing diversion of controlled substances, and to standard medical
practices intended to maintain sterility of the drugs. This has put
compounding pharmacists in the untenable position of following
universally accepted medical practice and risking enforcement action by
the DEA; or, undergoing an expensive and burdensome manufacturer
registration process that does not accurately reflect the status of
their traditional pharmacy practice.
Alternatively, they could refuse to fill prescriptions for
controlled substances for office administration, which could jeopardize
patient access to critical medications. Again, changes to the FDCA or
CSA should be consistent in what actions trigger manufacturer licensing
requirements and should not impede traditional pharmacists from
compounding patient-specific medications for office administration when
medically necessary.
With regard to standards for sterile and non-sterile compounding,
IACP feels that these issues are sufficiently addressed by State laws
and regulations. Where it is not, IACP strongly urges that States adopt
rules and regulations similar to those in Iowa (Iowa regulations are
attached). IACP again encourages that the USP <795> and <797> standards
and practices be adopted by every State, as further safeguard.
State Boards must ``police'' themselves and provide the necessary
assurances to other State Boards which depend upon them for conducting
inspections for non-resident pharmacies in a regular and consistent
manner. Massachusetts Board obviously failed to execute its
responsibilities both to its citizens as well as patients in other
States in which NECC was licensed by not conducting regular
inspections.
Additionally, virtually every State requires an out-of-state
pharmacy to register as such with the recipient State (with one notable
exception being Massachusetts). In this regard, the pharmacy dispensing
compounds across State lines is subject to heightened (not diluted)
oversight and regulation because it must abide by the laws of both its
home State and the out-of-state recipient.
With regard to the Active Pharmaceutical Ingredients (APIs) used in
the profession of compounding, there already exists in Federal statute
language that requires all drugs compounded in the United States to use
only active pharmaceutical ingredients (APIs) from FDA registered
facilities. (See section 510). IACP regularly reminds its members to
require a bill of lading. This provision was included in the PDUFA
reauthorization legislation signed into law this year. Please see below
for statutory language:
P.L. 112-144, Section 713, The ``Food and Drug
Administration Safety and Innovation Act''.
SEC. 713. STANDARDS FOR ADMISSION OF IMPORTED DRUGS.
Section 801 (21 U.S.C. 381) is amended--
(1) in subsection (o), by striking ``drug or''; and
(2) by adding at the end the following:
(r)(1) The Secretary may require, pursuant to the
regulations promulgated under paragraph (4)(A), as a condition
of granting admission to a drug imported or offered for import
into the United States, that the importer electronically submit
information demonstrating that the drug complies with
applicable requirements of this Act.
(2) The information described under paragraph (1) may
include--
(A) information demonstrating the regulatory status of
the drug, such as the new drug application, abbreviated
new drug application, or investigational new drug or
drug master file number;
(B) facility information, such as proof of
registration and the unique facility identifier;
(C) indication of compliance with current good
manufacturing practice, testing results, certifications
relating to satisfactory inspections, and compliance
with the country of export regulations; and
(D) any other information deemed necessary and
appropriate by the Secretary to assess compliance of
the article being offered for import.
(B) PROCEDURE.--In promulgating a regulation under
subparagraph (A), the Secretary shall--
(i) issue a notice of proposed rulemaking that
includes the proposed regulation;
(ii) provide a period of not less than 60 days for
comments on the proposed regulation; and
(iii) publish the final regulation not less than 30
days before the regulation's effective date.
(C) RESTRICTIONS.--Notwithstanding any other provision of
Federal law, in implementing this subsection, the Secretary
shall only promulgate regulations as described in subparagraph
(B).
(3) DISCONTINUANCE OF REGISTRATION.--The Secretary shall
discontinue the registration of any commercial importer of drugs that
fails to comply with the regulations promulgated under this subsection.
(4) UNIQUE FACILITY IDENTIFIER.--The Secretary shall specify the
unique facility identifier system that shall be used by registrants
under paragraph (1). The requirement to include a unique facility
identifier in a registration under paragraph (1) shall not apply until
the date that the identifier system is specified by the Secretary under
the preceding sentence.
(5) EXEMPTIONS.--The Secretary, by notice in the Federal Register,
may establish exemptions from the requirements of this subsection.
(c) MISBRANDING.--Section 502(o) (21 U.S.C. 352) is amended by
inserting ``if it is a drug and was imported or offered for import by a
commercial importer of drugs not duly registered under section
801(s),'' after ``not duly registered under section 510.''
(d) REGULATIONS.--
(1) IN GENERAL.--Not later than 36 months after the date of the
enactment of this Act, the Secretary of Health and Human Services, in
consultation with the Secretary of Homeland Security acting through
U.S. Customs and Border Protection, shall promulgate the regulations
required to carry out section 801(s) of the Federal Food, Drug, and
Cosmetic Act, as added by subsection (b).
(2) PROCEDURES FOR PROMULGATING REGULATIONS.--
(A) IN GENERAL.--In promulgating a regulation under paragraph (1),
the Secretary shall--
(i) issue a notice of proposed rulemaking that includes the
proposed regulation;
(ii) provide a period of not less than 60 days for comments on the
proposed regulation; and
(iii) publish the final regulation not less than 30 days before the
regulation's effective date.
(B) RESTRICTIONS.--Notwithstanding any other provision of Federal
law, in implementing section 801(s) of the Federal Food, Drug, and
Cosmetic Act, as added by subsection (b), the Secretary shall
promulgate regulations only as described in subparagraph (A).
On the issue of where and with whom a pharmacy should be
registered, pharmacies are already required to register with their
State Board of Pharmacy and the Drug Enforcement Administration (DEA).
Adding an additional registration requirement for pharmacies would do
nothing to further the goal of keeping patients safe--it would amount
to a paperwork requirement/administrative step that would produce no
particular positive outcome due to an already overstrained FDA budget
and the existing broad categories of oversight the agency has to
prioritize.
The FDA may inspect an establishment--including pharmacies--to
ensure that drugs are appropriately handled and stored. In other words
. . . they can look at what's on the shelf, in the refrigerator, in the
inventory, etc.
The FDA may not inspect records and files (e.g., prescriptions,
compounding formulas, etc.) unless either (a) the pharmacy in
noncompliant with its State laws, see supra section 704 discussion, or
(b) FDA has an administrative warrant that demonstrates a sufficient
cause to do so. A pharmacy may decline such an inspection if it
believes it is operating in full compliance with the State law unless
there is some sort of court document authorizing the FDA to do so.
However, if the pharmacy is registered as a manufacturer, the FDA
has much broader authority to inspect and cite such a manufacturing
entity. As a manufacturer, they would also have to comply with CGMP and
the FDA has clear injunctive authority over them, should they not
remedy violations. In short, a pharmacy engaged in manufacturing is
subject to the same laws, inspections, restrictions, and penalties as a
commercial drug manufacturer.
There are many patients (both human and animal) needing products in
various medical scenarios requiring physician input and judgment based
upon the needs of their patient. States already have limitations to
this in their regulations and laws as necessary for their particular
State for citizens/citizens' pets. Pharmacists are required, by State
law, to have sufficient drugs and preparations on their shelves to
enable them to service their clients in a timely manner. Any
requirement that a pharmacist must wait on each and every prescription
thus works counter to public interest and patient health and safety.
Regarding the prescription, moreover, there is no need for a
physician to explicitly order a compounded drug. If a physician orders
a name brand commercial product, the pharmacy will fill the
prescription with it. If, however, the physician's prescription is
specific as to active ingredient, dosage, and/or delivery format, it
enables the pharmacy to create the medication as needed for the
particular patient, and as a prescribed physician, without need of
express direction to compound by the physician.
IACP acknowledges that many States have already addressed this
issue through ``office use'' specifications in their laws and
regulations (IACP has supplied the committee with a state-by-state
office use regulation guide). Should a State NOT have such standards in
place, IACP would urge the State to adopt clear and concise guidance
for the compounding of medications for ``office use.'' IACP adds that
compounds prepared for office stock are no different than a singular
compounded drug prescription in terms of pharmacy preparation. The same
State law remains applicable to each and every one of these compounds.
Finally, regarding labeling, please see the enclosed IACP statement
regarding suggested labeling for office use.
Ultimately, the decisionmaking with regard to what a script
requires is left to the medical practitioner who writes the scripts in
the first place. The doctor or veterinarian is best educated and best
suited to make these determinations on medicines to be used and in what
dose and dosage form. IACP does not believe the volume of prescriptions
involved necessarily is the issue. Instead, the issue is one of (a)
drug preparation--which is the same regardless of number, and (b)
fulfilling the medical judgments of the practitioner by following the
practitioner's directions, as determined for the practitioner's
patient.
IACP believes that the FDCA's existing inspection provision,
section 704, which was outlined supra, allows FDA the necessary
authority and oversight it needs to determine whether a pharmacy is
operating as a pharmacy or, instead, akin to a drug manufacturer, thus
subjecting it to full inspection and FDCA application.
By way of further example, FDA may inspect the equipment, drug
materials, containers and labeling of any pharmacy. See section 704(a)
(sentence one). State law requires pharmacy labeling to include, inter
alia, the name and strength of the active ingredient, the lot number,
the beyond-use date, the quantity or amount in the container, the
pharmacy's name, and the physician's name.
Through this information, FDA can assess the professionals'
licensure, the exact prescription for the patient, and exactly what the
patient will receive. Moreover, all this information must be included
on the label or the pharmacy violates its State's law, thus triggering
the FDCA section 704 enhanced inspection (sentence three) that applies
to drug manufacturers. (See section 704(a)(2)(A)).
It has not been IACP's experience that the FDA has had difficulty
collaborating with the States. The opposite appears to be true. FDA
often collaborates with both the State boards of pharmacy and the DEA,
both of which have full inspection authority over pharmacies. See e.g.,
Wedgewood Village Pharmacy, Inc. v. U.S., 421 F.3d 263, 271 (2005)
(noting FDA collected all the evidence it needed regarding whether a
pharmacy was operating as a pharmacy or more akin to a manufacturer
through collaboration with the State board and DEA); and Medical Center
Pharmacy v. Mukasey, 451 F.Supp.2d 854 (W.D.Tex. 2006) (noting same).
IACP stresses the importance of communicating important health
information to patients whenever any medication is dispensed through
labeling on the medication. IACP supports State regulations that
require information on labeling that informs the patient that the
medication has been compounded.
With regard to adverse event reporting, IACP argues that MedWatch
is the Food and Drug Administration's reporting system for an adverse
event or sentinel event, founded in 1993. This system should also be
used for compounded medication.
An adverse event is any undesirable experience associated with the
use of a medical product. The MedWatch system collects reports of
adverse reactions and quality problems, primarily with drugs and
medical devices, but also for other FDA-regulated products (e.g.,
dietary supplements, cosmetics, medical foods, and infant formulas).
Voluntary reporting by healthcare professionals, consumers, and
patients is conducted on a single, one-page reporting form (Form FDA
3500). Reporting can be conducted online, by phone 1-800-FDA-1088, or
by submitting the MedWatch 3500 form by mail or fax 1-800-FDA-0178.
Rather than replicating The MedWatch system, IACP contends that
there already exists a reporting system for all in the Triad of care.
MedWatch is intended to detect safety hazard signals for medical
products. If a signal is detected, the FDA can issue medical product
safety alerts or order product recalls, withdrawals, or labeling
changes to protect the public health. Important safety information is
disseminated to the medical community and the general public via the
MedWatch Web site and the MedWatch E-list.
On the issue of communication between agencies, IACP would support
a notification system that requires States to notify the FDA (within 14
days of such action) when a pharmacy's license has been revoked.
Additionally, the FDA should notify States when they believe a pharmacy
is acting as a manufacturer and may be operating outside of its
registration status allowances.
Additionally, Congress might want to consider assessing civil
penalties when a pharmacy owner/operator has willfully misled
authorities as to the nature of their business.
IACP appreciates this opportunity to provide input on this critical
outbreak to the committee and looks forward to further discussing this
issue. IACP will be happy to respond to any additional questions the
committee may have.
The Chairman. Thank you, Mr. Miller.
Now we'll turn to Dr. Thompson.
Dr. Thompson, please proceed.
STATEMENT OF KASEY K. THOMPSON, PHARM.D., M.S., B.S., VICE
PRESIDENT, OFFICE OF POLICY, PLANNING AND COMMUNICATIONS,
AMERICAN SOCIETY OF HEALTH-SYSTEM PHARMACISTS, BETHESDA, MD
Mr. Thompson. Thank you, Chairman Harkin and distinguished
members of the committee, for holding this hearing. My name is
Kasey Thompson. I am vice president for Policy, Planning, and
Communications with the American Society of Health-System
Pharmacists. I am here today to provide ASHP's perspective on
the recent meningitis outbreak and to explore potential policy
options to help prevent similar events from occurring ever
again in the future.
First and foremost, on behalf of ASHP and our more than
40,000 members practicing in hospitals, health systems, and
ambulatory clinics, I want to express our sympathy for the
victims and their families who were harmed by this terrible
tragedy. The patients who relied on these medications deserved
much better.
Unfortunately, the New England Compounding Center appeared
to have been operating in a manner that falls far short of
standards for compounding sterile preparations. Further, the
scale and scope of NECC's operations more nearly resembles
pharmaceutical manufacturing than traditional pharmacy
compounding.
U.S. hospitals prepare a vast array of compounded sterile
preparations every day in order to meet the needs of patients.
In fact, the majority of compounded medications hospitals
utilize are prepared in-house by pharmacy departments. The
compounded medications that hospitalized patients need include
simple intravenous admixtures to complex customized medications
that are not available off the shelf, such as multi-ingredient
solutions for heart surgery, epidural pain medication, and
adult medications prepared with concentrations that can be
safely administered to babies and children.
However, hospitals also enlist the help of qualified
compounding pharmacies for some compounded preparations for
several reasons. For example, they may not have the necessary
equipment or facilities to prepare some high-risk preparations,
or they may face medication shortages from commercial products.
Hospitals prepare or purchase compounded medications based
on specific patient needs and individual medication orders or
in anticipation of needs for patients under their care.
Importantly, medications that are purchased from outside
compounding pharmacies are not commercially available from
brand or generic manufacturers in the individualized form
needed for specific patients.
ASHP has dedicated itself to developing the highest
standards for compounding sterile products in hospitals. We
began publishing guidelines on sterile and non-sterile
compounding in the early 1990s. In 2010, ASHP published the
ASHP Guidelines on Out-
sourcing Sterile Compounding Services to advise pharmacy
departments on how to conduct due diligence when selecting
outsourcing vendors. All of our guidelines have always been
available as a free public service to the healthcare community
and to others.
However, even with the availability of these useful
resources, we cannot rely solely on the diligence of purchasers
to take the place of proper licensing, inspection, and
oversight of entities producing compounded medications,
especially those entities that are manufacturing in large
quantities and shipping across the country. Pharmacists and
other healthcare providers should not be expected to perform
the jobs of regulators by visiting and inspecting pharmacies
and manufacturers that they do business with.
The distinction between traditional pharmacy compounding
and manufacturing appears to be a regulatory gray area between
State boards of pharmacy and the FDA. As we have seen, however,
the implications of this gray area are serious.
We recognize the regulatory challenges of defining the
activities in this gray area. We firmly believe that specific
definitions are essential so that mass production of the scope
and scale done by NECC falls clearly within the regulatory
jurisdiction of FDA rather than State boards of pharmacy. To
this end, we have developed policy recommendations for the
committee, FDA, and other stakeholders to consider as we
explore ways to address this gap in oversight.
A number of variables make distinguishing between compound-
ing and manufacturing difficult. Therefore, both functions
might be better viewed as a continuum of activities stratified
by the potential risk for patient harm, each requiring defined
procedures, equipment, training, and quality controls. At one
end of the continuum, oversight of traditional compounding is
clearly within the purview of States and the oversight of
pharmaceutical manufacturing within the purview of the FDA.
Once compounding activities advance along the continuum to
manufacturing, the risk to patient safety and public health
increases. There may be a need for a special category of FDA
oversight that falls between compounding and manufacturing but
does not require a drug approval.
For example, if a compounding pharmacy sells to other
organizations and not directly to patients, there may be a need
to be regulated by the FDA. Doing so would allow hospitals,
clinics, and physician offices to purchase sufficient
quantities of compounded product as is necessary to meet
patient needs, while doing so under the assurance that they are
making those purchases from appropriately regulated entities.
ASHP recommends stronger communication and collaboration
between State boards of pharmacy and the FDA to accomplish this
goal. We also believe that State boards of pharmacy should be
able to work with FDA to inspect an entity suspected of
engaging in large-scale drug production beyond the scope of
traditional pharmacy compounding.
Finally, we strongly believe the FDA must be provided with
the resources it needs to perform oversight of compounding
entities that are potentially engaged in manufacturing.
Thank you for the opportunity to provide the perspectives
of the pharmacists who practice in hospitals and health
systems. ASHP remains committed to working with Congress, the
FDA, and other stakeholders to ensure that an event like this
never occurs again.
[The prepared statement of Mr. Thompson follows:]
Prepared Statement of Kasey K. Thompson, Pharm.D., M.S., B.S.
summary
U.S. hospitals prepare a vast array of compounded sterile
preparations every day in order to meet the needs of patients. However,
hospitals also enlist the help of qualified compounding pharmacies for
some compounded preparations for several reasons.
ASHP has dedicated itself to being a leader in developing the
highest standards for compounding and sterile product preparation in
hospitals. We have developed an assessment tool based on our guidelines
that helps pharmacists in hospitals and health systems comprehensively
evaluate sterile compounding service providers and use comparative date
for their vendor selection process.
However, we cannot solely rely on the due diligence of purchasers
to take the place of proper licensing, inspections and oversight of
entities producing compounded medications. The distinction between
traditional pharmacy compounding and manufacturing appears to be a
regulatory gray area between State boards of pharmacy and FDA. As we
have seen, however, the implications of this gray area are serious.
ASHP recommends stronger communication and collaboration between
State boards of pharmacy and the FDA. We also believe that it may be
necessary to revisit previous attempts to further define pharmacy
compounding from large scale, mass-produced medications. Finally, we
strongly believe that FDA must be provided the resources it needs to
perform serious and meaningful regulatory oversight.
______
Good morning and thank you Chairman Harkin, Ranking Member Enzi,
and distinguished members of the committee, for holding this hearing.
My name is Kasey Thompson and I am vice president of Policy, Planning
and Communications for the American Society of Health-System
Pharmacists (ASHP). I am here today to provide ASHP's perspective on
the recent meningitis outbreak, and to explore potential policy options
to help prevent similar events from occurring in the future.
First and foremost, on behalf of ASHP and our more than 40,000
members practicing in hospitals, health systems, and ambulatory
clinics, I want to express our sympathy for the victims and their
families who were harmed by this tragedy. The patients who relied on
these medications deserved much better. Unfortunately, the New England
Compounding Center appeared to have been operating in a manner that
falls far short of standards for compounding sterile preparations.
Further, the scale and scope of NECC's operation more nearly resembles
pharmaceutical manufacturing rather than pharmacy compounding.
U.S. hospitals prepare a vast array of compounded sterile
preparations every day in order to meet the needs of patients. In fact,
the majority of compounded medications hospitals utilize are prepared
in-house by pharmacy departments. The compounded medications that
hospitalized patients need span from simple intravenous admixtures to
complex customized medications that are not available off the shelf,
such as multi-ingredient cardioplegia solutions for heart surgery,
precisely measured combinations of epidural pain medication and adult
medications prepared in concentrations that can be safely administered
to babies and children.
However, hospitals also enlist the help of qualified compounding
pharmacies for some compounded preparations for several reasons. For
example, they may not have necessary equipment or facilities to prepare
some high-risk preparations, or they may face medication shortages for
commercial products that can only be replicated by a compounding
pharmacy.
Hospitals prepare or purchase compounded medications based on
specific patient needs and individual medication orders or in
anticipation of needs for patients under their direct care.
Importantly, medications that are purchased from outside compounding
pharmacies are not commercially available from brand or generic
manufacturers in the individualized form needed for a specific patient
or patients, unless manufacturers cannot supply them.
ASHP has dedicated itself to developing the highest standards for
compounding and sterile product preparation in hospitals. Through our
peer-reviewed publication, the American Journal of Health-System
Pharmacy, we began publishing guidelines on sterile and non-sterile
compounding in the early 1990s. In 1993 we published the ASHP Technical
Assistance Bulletin on Quality Assurance for Pharmacy-Prepared Sterile
Products. This was revised in 2000, and is currently in the final
stages of revision.
These guidelines formed the basis for the three-tier risk
assessment structure later incorporated by the United States
Pharmacopeia into Chapter 797, its standards for compounding sterile
products. In 2010, ASHP published the ASHP Guidelines on Outsourcing
Sterile Compounding Services to advise pharmacy departments on how to
conduct due diligence when selecting outsourcing vendors. In addition,
we have developed an assessment tool based on our guidelines that helps
pharmacists in hospitals and health systems comprehensively evaluate
sterile compounding service providers and use comparative data for
their vendor selection process. Our guidelines and assessment tool are
and have been available free as a public service to the health care
community and others.
policy options
We cannot rely solely on the due diligence of purchasers to take
the place of proper licensing, inspections and oversight of entities
producing compounded medications, especially for those entities that
are manufacturing in large quantities and shipping across the country.
Pharmacists and other health care providers should not be expected to
perform the jobs of regulators by visiting and inspecting pharmacies or
manufacturers that they do business with.
The distinction between traditional pharmacy compounding and
manufacturing appears to be a regulatory gray area between State boards
of pharmacy and FDA. As we have seen, however, the implications of this
gray area are serious.
We recognize the regulatory challenges of defining the activities
in this gray area, but we firmly believe that specific definitions are
essential so that mass production of the scope and scale done by NECC
falls within the regulatory jurisdiction of FDA, rather than State
boards of pharmacy. To this end, we have developed policy
recommendations for the committee, FDA and other stakeholders to
consider as we explore ways to address this gap in oversight.
Previous attempts to define compounding in Federal law contained
certain elements that should be examined in light of practice changes
since 1997. Recent legislative proposals merit further discussion and
exploration, since they may reflect those practice changes and allow
for the regulatory flexibility among State boards of pharmacy and the
FDA that would ensure that hospitals continue to be allowed to obtain
compounded medications in anticipation of patient need.
Compounding pharmacies range from small pharmacy operations that
compound medications for individual patients directly under their care
to large-scale operations that prepare compounded medications in the
volumes required to serve the needs of patients under the care of
health systems or physician offices. A number of variables make
distinguishing between compounding and manufacturing difficult.
Therefore, both functions might be better viewed as a continuum of
activities stratified by the potential for risk of patient harm, each
requiring defined procedures, equipment, training, and quality
controls. At one end of the continuum, oversight of traditional
compounding is clearly within the purview of States, as is FDA
regulation at the other end of the continuum with pharmaceutical
manufacturing. As legislative proposals are considered, it will be
important to reaffirm the role of State boards of pharmacy to license
and regulate traditional compounding while recognizing that large-scale
compounding of sterile products may require oversight by the FDA in
cooperation with State boards of pharmacy.
Once compounding activities advance along the continuum to
manufacturing and the risk to patient safety and public health
increases, there may be a need for a special category of FDA oversight
that falls between compounding and manufacturing but does not require a
drug approval (e.g., an NDA). For example, if a compounding pharmacy
sells to other organizations and not directly to patients, then they
may need to be regulated by the FDA. Doing so would allow hospitals,
clinics, and physician offices to purchase sufficient quantities of
compounded product as is necessary to meet patient needs, while doing
so under the assurance that they are making those purchases from
appropriately regulated sources.
ASHP recommends stronger communication and collaboration between
State boards of pharmacy and the FDA to accomplish this goal. We also
believe that State boards of pharmacy should be able to work with FDA
to inspect an entity suspected of engaging in large-scale production
beyond the scope of pharmacy compounding. Previous court rulings have
made FDA's authority to inspect these facilities unclear and subject to
legal action.
Finally, we strongly believe that FDA must be provided the
resources it needs to perform serious and meaningful regulatory
oversight of entities that are potentially engaged in manufacturing.
Not to do so now will only hinder the agency in implementing
legislation.
conclusion
To summarize, we are profoundly saddened by what we believe should
have been an avoidable tragedy. ASHP remains committed to working with
Congress, FDA and other stakeholders to address these regulatory gaps
and reduce the likelihood of similar outbreaks from compounded sterile
products in the future.
The Chairman. Thank you very much, Dr. Thompson. We'll
begin a round of 5-minute questions.
Mr. Miller, do you believe Congress should clarify the
legal status of section 503A given the current split between
the Ninth and Fifth Circuits?
Mr. Miller. Mr. Chairman, there is definitely clear
confusion about authority based upon the judicial decisions in
the Fifth and the Ninth. We also know based upon the Medical
Center v. Thompson decision in the Supreme Court that actually
struck down sections of the original FDA FDAMA law as being
unconstitutional. So, yes, we need to go back and revisit this,
especially in light of this tragedy.
The Chairman. Let me ask that question one more time. Do
you believe Congress should clarify the legal status of section
503A?
Mr. Miller. Yes.
The Chairman. Thank you. That's all I wanted to hear. We
know the background and stuff. We're trying to get a
clarification of this. So you think that we should give that
kind of clarification whether it's the flagpole type or some
kind of clarification on section 503A?
Let me ask this. I may tend to disagree with you a little
bit on your sort of absolute statement that FDA had
jurisdiction in this. I still think that's sort of a gray area.
But let's assume that they did.
Mr. Miller. Yes, sir.
The Chairman. Assuming we agree that they should have
jurisdiction when a pharmacy like NECC operates in a manner and
scale that is essentially a manufacturer, shouldn't the FDA
have access to records such as prescription records to help it
determine whether the operation is really a compounder or a
manufacturer?
Mr. Miller. That's a complex question, and the answer is it
does. The FDA has the ability to obtain a court order,
subpoena, or administrative warrant to obtain any records
within a pharmacy. They also have the ability to work in
collaboration with a board of pharmacy. The board of pharmacy
in every State has the ability to look at all documentation and
materials in any of its licensed sites.
If the FDA felt compelled, in addition to its Form 482 on-
site inspection of materials, that it needed additional
information, that's a simple collaboration with a State board
of pharmacy. We know based on testimony that occurred between
the FDA and the Massachusetts Board of Pharmacy, and yet that
system still failed. Does the FDA--should they--actually,
Senator, although it's not specific, they do have that ability
currently.
The Chairman. They do have to go through a lot of hoops.
They've got to go to court. They've got to get all kinds of
things before they do that. That takes, obviously, a lot of
resources. It takes a lot of time. I'm just saying that if we
agree that FDA should have this jurisdiction, shouldn't they
have access to records to help them determine whether it's a
compounder or a manufacturer, because sometimes--as Dr. Hamburg
kept saying, sometimes they don't know.
Mr. Miller. Yes. One of the things that also has to be
addressed--and it's very important--is that as we distinguish
between a pharmacy engaged in compounding, which more than 50
percent of all pharmacies in the country do, versus
manufacturing, we have to look at what they are doing, not
necessarily how, but what are they doing.
The Chairman. I know you were here for the first panel. You
may have heard me say something about State lines.
Mr. Miller. Yes.
The Chairman. I don't know if that's right or not. What are
the features that distinguish NECC from what you would view as
a legitimate large-scale compounding pharmacy? Again, we heard
about volume. I mentioned interstate shipment, prescription
records. Again, do we have some guidelines? What features would
distinguish that as a legitimate large-scale compounding
pharmacy?
Mr. Miller. Mr. Chairman, I am a pharmacist. I tend to
think black and white. The answer is pretty simple. When I
receive a prescription, regardless of whether it's a compound
or an off-the-shelf commercially manufactured drug, that is
coming from an authorized prescriber in my State. I'm empowered
to fill it for a patient, or, depending upon the order, I may
be filling it for a clinic associated with a hospital down the
street. I fill prescriptions.
The difference between NECC and a compounding pharmacy was
they weren't filling prescriptions. They were bulk
manufacturing and selling. A company like Pfizer creates and
sells medications. They don't fill prescriptions. A company
like Ameridose, associated with NECC, creates and sells
medications. Pharmacies fill prescriptions.
One of the things that we've heard from conversations with
many boards of pharmacy is how do I distinguish this? It's
relatively simple. Any pharmacy inspector, specifically one who
is a pharmacist and trained, can tell you, based on the
paperwork in that pharmacy, is this pharmacy filling a
prescription, or are they essentially creating bulk quantities?
And those bulk quantities, whether they're 100 or 100,000--are
they being sold as opposed to being dispensed?
It's a function of what we do as pharmacists that really
differentiates between pharmacy practice and manufacturing.
That's where I think we really went awry here with NECC,
because it was quite apparent that they were not filling
prescriptions. They were selling stuff, and that's what
manufacturers do.
The Chairman. OK. I'll try to absorb all that.
Senator Roberts.
Senator Roberts. I want to be a little insistent here, and
I apologize for that. In the first place, in my opening
statement, I said that I hoped that the witnesses today would
offer their commitment to work with us--and I think you've done
that--and to do so in good faith--and I know you'll do that--
with the intent to be transparent and forthcoming with your
thoughts and your suggestions and your concerns. That came from
my opening remarks.
Is this something that you are both willing to do,
remembering that during the early days of trying to get
something done, we wanted answers and all we got was pushback.
Could you speak to that, please?
Mr. Miller. Senator Roberts, as a pharmacist and as an
organization representing pharmacists, the worst possible thing
has happened. We have more than 30 people dead. We have 461
people ill. Right now, the focus must be on working
collaboratively--professional associations, regulators,
legislators--to prevent this from ever happening again. IACP
and all the other pharmacy associations, State and national,
will be working with you, this committee, and everyone else to
make sure that we protect the public from organizations,
businesses, entities like an NECC. You have my commitment on
that, Senator.
Senator Roberts. I appreciate that.
Dr. Thompson, I know that you are providing a legislative
blueprint to be of help to us, which I appreciate. Is that
criteria voluntary, or is that mandatory?
Mr. Thompson. The blueprint that we suggested?
Senator Roberts. Yes.
Mr. Thompson. We think that's mandatory. Basically, it's to
clarify the jurisdiction of the FDA over manufacturing of these
compounding entities. I call them entities for a reason,
because it is a gray area--and I'm speaking as a practitioner
and for our members--in trying to understand who they're doing
business with out there. And we do believe there are some gray
areas.
We think that this is something that would give the FDA the
authority it needs to regulate these entities that fall between
the Pfizers and the Mercks and the large-scale manufacturers
that are manufacturing under approved drug applications and
abbreviated new drug applications for generic drugs and these
entities that are compounding medications in large amounts.
Senator Roberts. In your opinion, either one of you, do you
think that NECC is a manufacturer? If you do, do you believe
that FDA has the current oversight and enforcement authority to
appropriately regulate manufacturers?
Mr. Thompson. I believe that they were behaving as a
manufacturer, without question. It's become clear to me, or
perhaps unclear, whether FDA had the authority or not. This
registration that compounding pharmacies do with the FDA is not
the same as what a commercial manufacturer that is
manufacturing under a new drug application and is licensed to
manufacture under that application. I do believe it's a
regulatory gray area that must be confirmed by Congress.
Mr. Miller. No question, Senator. NECC was engaged in
illegal manufacturing. They did not have a license in the State
of Massachusetts as a manufacturer. All States oversee that, in
addition to the FDA. They were not registered with the FDA.
They were shipping products nationwide without prescriptions,
without official authorized orders from prescribers. Bottom
line, that's manufacturing.
Senator Roberts. I appreciate that. I have no further
questions, Mr. Chairman.
The Chairman. Senator Alexander.
Senator Alexander. Thanks, Mr. Chairman.
Thank you for being here and for your testimony. You make
the solution sound pretty simple, that you just take these
large facilities that are in the gray area, and some of them
are manufacturers and they're regulated by the FDA, and the
rest of them aren't. They're filling prescriptions and they're
regulated by State boards of pharmacy. Am I hearing you right?
Mr. Miller. From--go ahead, Kasey.
Mr. Thompson. I'm sorry. Yes, you are hearing me correctly
in that respect. We do believe that traditional pharmacy
compounding is the filling of a prescription and dispensing
that to a patient. These entities that are preparing large
amounts of medications and not necessarily dispensing those to
patients but selling those to various entities, whether it's
hospitals, physician offices or others, are manufacturing.
Senator Alexander. There are some--let's take Tennessee.
Maybe we've got 1,000 to 1,200 pharmacies. Let me just guess at
it. And based upon your testimony, maybe 500 of them do
compounding.
Mr. Miller. That's correct.
Senator Alexander. Now, apparently, there must be a number
of other larger compounding pharmacy facilities in Tennessee,
for example. Would that be true? Anybody know? I have some
suggestions here that there may be 7,500 pharmacies that
specialize in advanced compounding, 3,000 that provide sterile
compounding. Are these just large drug stores that we're
talking about, or are these large entities or companies that
fill prescriptions, that do advanced sterile compounding and
still fill prescriptions? How many are we talking about here?
Mr. Miller. Senator, thank you. I can answer that. Those
statistics actually come from the International Academy of
Compounding Pharmacists. The 7,500 and 3,000 you've heard
mentioned are actually our statistics.
There are compounding pharmacies, sterile compounding
pharmacies, in the State of Tennessee, actually, quite a few of
them. Some are large. Some are relatively small. One of the
things I don't want us to get too hung up on is the issue of
size, because size does not necessarily mean that you're a
manufacturer. It's actually what you do--Senator Harkin, to
what I was saying before.
Senator Alexander. There might be 40 or 50 in Tennessee,
roughly. We're usually 2 percent of everything, so if there are
3,000 sterile manufacturers, there might be 40, 50 or 60 of
varying sizes. Is that right?
Mr. Miller. Sterile compounding pharmacies, not
manufacturers.
Senator Alexander. Sterile compounding pharmacies.
Mr. Miller. Yes, sir. What we have to recognize is they may
be part of a hospital. They may be part of a home infusion
company that specializes in outpatient, a nursing home, long-
term care, or it could be affiliated with one of our major
chains. It could be a standalone, community-based pharmacy.
Senator Alexander. These are the ones we're talking about
here. We're not talking about the 1,000 pharmacies that are
doing traditional compounding, or we're not talking about
manufacturers who are selling in bulk. We're talking about, in
my State, maybe 40, 50, or 60 entities of various sizes which
are compounding pharmacies, some of them doing sterile work.
Mr. Miller. Actually, you have more than that in terms of
compounding, in general. That estimate for sterile compounding
in your State--I would say that's extremely accurate. Those are
the pharmacies we would want to make sure are identified by
your State.
Senator Alexander. That's where the potential trouble is,
insofar as this incident is concerned. Is that right?
Mr. Miller. My hesitation isn't because I don't agree. I'm
concerned that that may be too narrow of an interpretation.
Senator Alexander. Let me ask it this way, then. The
trouble is the lack of clarity about who's on the flagpole.
Mr. Miller. Yes, sir.
Senator Alexander. If I can understand--let's just narrow
it down to these, let's say, 50 advanced compounding facilities
in Tennessee. That gets rid of most of the drug stores in
Tennessee, and it gets rid of all the manufacturers. We're
talking about 50. How do we decide who regulates those 50? Does
the State board of pharmacy do it, or does the FDA do it?
Mr. Miller. Right now?
Senator Alexander. Well, no. How should it be? How should
it be going forward?
Mr. Miller. To identify them, I would send the State board
of pharmacy in to inspect all of them. That State board
inspector should be able to determine is this pharmacy a
pharmacy, or is this pharmacy actually engaged in
manufacturing.
Senator Alexander. What if they're as incompetent as the
State Board of Pharmacy of Massachusetts seemed to be over the
last 10 years?
Mr. Miller. Then we have a very significant problem.
Fortunately, that doesn't seem to be the case in most States.
One of the recommendations our organization has at the State
level is we need to adequately fund our boards and provide them
with inspectors who are trained and kept up-to-date so they can
go in and review a pharmacy so that we can identify and prevent
an NECC----
Senator Alexander. I interrupted you. You were saying you
would send the State board of pharmacy in to decide, first, are
they pharmacies, or are they manufacturers?
Mr. Miller. That's correct.
Senator Alexander. Then what?
Mr. Miller. If they are identified as being a manufacturer
outside of the practice of pharmacy and the rules and
regulations within the State, the State board has the ability
to shut them down, discipline them, revoke their license,
suspend it, if they believe--the State board, just as Colorado
did with NECC--if they identify that pharmacy as a
manufacturer, they can cross-file that complaint, specifically,
with the FDA, who has the ability to shut down an illegal
manufacturer.
Senator Alexander. Yes.
Mr. Miller. So it's a combination of both----
Senator Alexander. Well, this is helping me. Sometimes when
we get these large, difficult questions, getting it down to a
quantifiable level helps. We're really talking about, in a
State like ours, what to do about 30, 40 or 50 institutions.
How do we identify them, and then how do we regulate them. If
we don't trust the State in every case, or don't trust the FDA
in every case--I would trust the Tennessee Board more than I'd
trust the FDA to identify them, to tell you the truth, based on
what I've heard today. But not Massachusetts.
So there we have the dilemma. I suppose with that smaller
number, you could allow the FDA to go in and make its own
judgment about whether they're manufacturers or not. If they
are, regulate them. You're saying have the State board go in
and decide it.
Mr. Miller. Senator, first off, the FDA can go into those
facilities, those pharmacies, at any time. No question about
that. If we wish to, from a policy standpoint, require that the
FDA inspect all potentially identified sterile compounding
pharmacies, that's a decision we could make as a policy.
Senator Alexander. That wouldn't be so many that it would
be an overwhelming number, would it? Or would it?
Mr. Miller. I can't answer that for the FDA. My biggest
concern would be----
Senator Alexander. We're just talking about identification.
Mr. Miller. Yes. The agency would need to not only identify
them, but also then deal with the fact that each State has
conflicting compounding guidelines. For example, in the State
of Tennessee, your board of pharmacy said clearly to all
licensees in January, ``No non-patient-specific prescriptions
in our State.'' Other States do permit that.
Senator Alexander. Why is that?
Mr. Miller. Why is that? Because the individual State board
of pharmacy makes a decision as to what is needed and how it
needs to be regulated to protect the citizens within their
State.
Senator Alexander. Well, I'm running a little bit over my
time here, Senator Harkin. It helps us, in terms of developing
a policy to solve the problem looking forward, to narrow it
down to the number of entities we're talking about. Perhaps we
could agree to exclude manufacturers and people who are
illegally manufacturing. They're just illegally manufacturing.
And then traditional compounding, we understand, exists.
To identify the number of entities that fall into this gray
area, how do we identify them, and then how do we regulate
them? One of the things I'm experimenting with in my mind is an
idea for these areas, such as sterile compounding, that sort of
area, where the FDA may have standards, and actually certify a
State to handle that narrow area of compounding and be able to
take it away.
For example, in the case of Massachusetts, had there been
such a structure existing, based upon what we've heard today, I
would say if the FDA had the authority, it should jerk the
ability of Massachusetts to deal with these sorts of entities
at least until Massachusetts cleaned up its act. On the other
hand, it should give Tennessee an award for working with the
CDC to move quickly to eliminate the spread.
Anything you could submit to the committee, to the
chairman, Senator Enzi, Senator Roberts, those of us who are
interested, identifying exactly the number of entities we're
dealing with and a practical way for identifying, with the end
result being that we have some agency clearly on the flagpole,
so when we come up here 6 months from now, we don't have one
saying, ``Yes, I had responsibility,'' and the other one
saying, ``Well, I had some, too''--I want one to say, ``It was
my fault, my job, my responsibility,'' or the other one saying,
``No, that's my fault,'' just as the head of the CDC said when
I asked her--I said, ``Whose job was it to let the world know
what happened?'' She said, ``That was my job.''
The Chairman. Thank you, Senator Alexander. We're preparing
this letter, as I mentioned earlier, to go out to all the State
boards of pharmacy. Please take a good look at that, and if
you've got some suggestions for other things that you might
want to go into that letter, please let us know. I'd like to
get it out as soon as possible.
Senator Alexander. Good. I'll look at it today.
The Chairman. Some of the things you brought up may not be
in there, and I want to have you take a look at that to see if
we need to put----
Senator Alexander. Thank you. Good.
The Chairman. I appreciate that very much.
I just wanted to ask Dr. Thompson--I read through your
testimony yesterday, and I'll just refer to it again, just
reviewing it. I know you're saying that hospitals and large
entities like that can't really ensure the inspections to make
sure that they're getting the right kind of products that are
sterile and everything like that.
It seems to me if hospitals are outsourcing compounding,
can't they take steps to ensure that they're buying from
suppliers who utilize sterile practices? It seems like--don't
take this wrong, but it seems like in your testimony you're
shoving it all off on the compounding pharmacies. Don't the
hospitals also, especially large entities, have a
responsibility? Can't they take steps to ensure who they're
buying from and that they're meeting good manufacturing
practices?
Mr. Thompson. Yes, sir, and I believe that many of them do.
They verify that they're licensed by the State board of
pharmacy. They look to see whether or not they're registered
with the FDA as a manufacturer, which is a regulatory gray
area. I've spoken with many pharmacists that do go out and
visit facilities.
As you can imagine, Senator Harkin, a small hospital in
Iowa with 25 beds or less----
The Chairman. Can't do that, no.
Mr. Thompson [continuing]. You know, flying to
Massachusetts. That's where the challenge comes in. I think
many do that. But, at the end of the day, they have to be able
to count on the regulatory apparatus, whether it be the State
or the FDA, to do their part. We don't inspect Pfizer to make
sure that their products--so that's sort of the point I was
trying to make.
The Chairman. I understand a small hospital in Tennessee or
Iowa can't do that. There are some big hospital chains, and
they buy a lot of product. A lot of the smaller hospitals would
rely upon their ability to make sure that from whom they're
buying is practicing good manufacturing practices.
Mr. Thompson. Oh, sure, absolutely. Many of them do that.
I've spoken with many hospital pharmacists that go out and look
at compounding pharmacies. It gets a little difficult when they
go into these manufacturing operations, because that's sort of
a different type of expertise--that somebody needs to inspect a
manufacturer. But many of them do that, to your point.
The Chairman. I also want to again say forthrightly about
compounding products that we think a lot about it as meeting
specific needs of individuals. It has to be prescription-based,
rather than just producing mass products. Compounding
pharmacies also fill a real niche in our society for meeting a
drug shortage that might happen at some time. They can step in
and do things right away and help us meet certain drug
shortages. That's just another valuable service that they
provide.
Dr. Kainer, I didn't ask you any questions, but, again,
more than anything, you illustrate the diligence and the
professionalism of our public health professionals in the
United States and the close cooperation between the State
departments of health and the CDC. To me--and I have looked at
different health systems around the world--our public health
system in this country, in terms of prevention and in terms of
immediate diagnosis--that's the wrong word--immediately finding
things that are happening--detection and response, beats
anything anywhere in the world.
We have to make sure that we continue to have adequate
funding so that we employ and hire the best possible
epidemiologists and other professionals. You exemplify that,
and I appreciate it very, very much.
Mr. Miller, thank you very much. The two responses that I
liked hearing from you today were, No. 1, on the clarification
on 503A, and in response to Senator Roberts that your
association will, indeed, work with us as opposed to what
happened a few years ago.
Mr. Miller. Absolutely, Senator.
The Chairman. That's good news.
Senator Alexander. Mr. Chairman.
The Chairman. Yes.
Senator Alexander. Mr. Chairman, something you said, might
provide an opportunity for Dr. Kainer to respond. I thought you
made a very good point. The hospitals and the clinics and the
physicians, particularly after this, who buy compounded
medicines will be on alert. Maybe there's something else that
the CDC or its associates could do to create a warning system.
For example, was there anything that went on over the last
10 years that we've heard about in Massachusetts with the New
England Compounding Center that could have been put up as a
yellow flag that a hospital, like the Saint Thomas pain clinic
might have known about before they bought that, just by
checking the internet?
Is there a system like that, Dr. Kainer? I thought Senator
Harkin's question was a very good one.
The Chairman. That's interesting.
Dr. Kainer. I'm not specifically aware of such a system
that occurs right now that is in the public, specifically on
identifying or having a warning signal for a hospital. They
have the 483 inspection reports that people can do. It's not
necessarily user-friendly or easy for hospitals.
If I may add, many of the physicians who ordered these
medications did not realize that they were ordering from a
compounding pharmacy. They actually thought that they were
purchasing things from a manufacturer. Alerting clinicians as
to what is the difference between a compounding pharmacy and a
drug manufacturer, what's the difference between a generic
medication versus a brand name medication, and compounded
products are not the same.
There's a lot of confusion among those providers. Perhaps
there's an opportunity here to educate the providers that there
is a difference between compounded products and manufactured
products.
The Chairman. That's very interesting. We should pursue
that, too. I was just told by my staff that many of the
documents that came out of the board in Massachusetts were not
public. There was no way for anybody out there, a hospital or
someone, to know that there were these indications. Maybe
that's something else we should look at.
Is there anything else that any of you want to impart to
the committee at all before we close it down? No?
Thank you all very, very much, each of you, for your
diligence, for being here, for adding to our deliberations. You
can sense that this is truly a bipartisan effort. This
committee will forge ahead in developing legislation, and,
toward that end, we again seek your input and your advice and
work with you to develop this legislation. Hopefully, we'll
have something soon next year that we'll be able to move ahead
on and put this sad chapter behind us.
Thank you all very much. I request that the record stay
open for 10 days to allow Senators to submit statements and
questions for the record.
With that, the committee will stand adjourned. Thank you
all very much.
[Additional material follows.]
ADDITIONAL MATERIAL
Prepared Statement of Senator Casey
Chairman Harkin, Ranking Member Enzi, I would like to thank
you for convening this investigative hearing. As members of the
Health, Education, Labor, and Pensions Committee, many from
States affected by this terrible tragedy, I believe we have a
duty to exercise our investigative and oversight authority, and
to make sure that we take every step possible to ensure that a
tragedy like the ongoing meningitis outbreak does not happen
again.
Like you, I am deeply disturbed by the long history of
problems at the New England Compounding Center, and concerned
that it took an event of this magnitude, with over 400 people
infected with a potentially lethal strain of meningitis and
over 30 having succumbed to its effects, to alert us to the
dangers of this company's practices.
In the face of this crisis, Pennsylvania has seen only one
case, compared to dozens of cases in the home States of some of
my colleagues on the committee. This outbreak has alerted us
all to the dangers to public health posed by bad actors in the
pharmacy compounding arena.
I know there are many good compounding pharmacists, and I
recognize the important role they play in ensuring that
patients have access to the drugs they need, when they need
them, and in the right form. Something went wrong at NECC, and
now over 30 people are dead as a result. We are here to learn
what led to this situation, and what we need to do to ensure it
never happens again.
There are many questions we have yet to answer, and we are
not sure what the best path forward will be. It is clear that
NECC was operating outside the bounds of Federal and State law.
Do we need greater Federal oversight of compounding pharmacies?
Do we need to require the FDA to work more closely with State
boards of pharmacy, and improve their communication? How have
the split district court decisions affected the FDA's ability
to take action with regard to compounding pharmacies?
There appears to be a lot of confusion surrounding the
regulation and oversight of these larger compounding pharmacies
that operate in the middle ground between traditional, small-
scale compounding pharmacies and large manufacturers. I believe
that everyone would benefit by reexamining current Federal law
and reevaluating whether our existing regulatory system is
appropriate for an industry that is changing and addressing new
challenges in our health care system. I know that this issue
has been contentious in the past, and I hope that all of the
interested parties will come together in good faith to protect
the public from future tragedies.
I look forward to hearing from our witnesses, I thank them
for sharing their expertise, and I thank Chairman Harkin and
Ranking Member Enzi for their commitment to protecting the
public from harm. I look forward to working with the other
members of the committee to clarify the law as it pertains to
compounding pharmacists.
------
______
Prepared Statement of John J. Dreyzehner, M.D., MPH, FACOEM,
Commissioner, Tennessee Department of Health, Nashville, TN
Please accept my sincere appreciation for your investigation into a
matter that has, regrettably, impacted thousands of Americans. Our
concerns and prayers for the patients, families and loved ones affected
by this preventable tragedy are continuing. On behalf of those who have
died or suffered physical and mental anguish, and their families and
friends who have also endured loss and anxiety, I thank you for your
work and assure you the Tennessee Department of Health is firmly
committed to working with you, our State legislators, the healthcare
community and other stakeholders to take this clear opportunity to do
all we can to assure this never occurs again.
As you know, healthcare and public health professionals in
Tennessee were the first in the Nation to detect, investigate and
understand what had gone horribly wrong in our clinics as a result of a
compounding pharmacy that now appears to have been acting as a
manufacturer in another State. Our investigation began Tuesday,
September 18, when an astute clinician provided the first indication of
something unusual in a patient's presentation and subsequent laboratory
evaluation. The finding of fungal meningitis launched a rapid
investigation that soon identified contaminated methylprednisolone
acetate (MPA) from the New England Compounding Center in Massachusetts
as the cause of an outbreak of meningitis, stroke and death for
patients who had received epidural steroid injections with the
egregiously tainted product at three facilities in our State.
I am proud of the work done in Tennessee to expeditiously identify
the contaminated medication which within 8 days of that first report
September 18th sparked a national recall of the three contaminated lots
of MPA. I am equally proud of work by the Tennessee Department of
Health, our central and local health department teams and our many
healthcare partners to rapidly find, reach out and provide close
assistance and regular contacts to more than 1,000 at risk individuals
and their families. I'm also proud of the cooperation among many States
in addressing this most serious outbreak. None the less, because this
whole tragic episode was preventable, I am not just saddened by the
occurrence, I am angered.
This does not appear merely to have been an unfortunate lapse or
error in pharmacy judgment or practice. It appears to have been a
cascade of increasingly serious and obvious omissions and commissions
that were persistently not addressed for reasons currently unknown. The
people who compounded these medications knew they were being relied
upon to be sterile by patients and clinicians--real people who trusted
them. This was a blatant disregard for health and safety by pharmacists
who should understand the potential consequences of the final
catastrophic failure that ultimately occurred. This was, at root, a
fundamental breach of an ethical duty and sacred obligation by the New
England Compounding Center to first, do no harm.
As a physician, my colleagues and I rely on a long-standing
foundation of trust and confidence in the drugs we administer to
patients, believing these materials are safe and effective and will
help, not hurt, an individual. I've talked with doctors who unknowingly
administered contaminated NECC products to the people they were trying
to help, and the impact to them is devastating. The men and women in
the medical community who trusted NECC products are among the victims
in this tragedy. We are angered by a few who failed to uphold the
integrity of critical processes, protocols and procedures, resulting in
harm to those we have pledged not to harm.
I turn now to the committee's specific questions. It is important
to retain the ability to compound medication. Compounding pharmacies
play a vital role in the practice of medicine. While the national
attention has focused on major compounding operations, most family
pharmacists across America are occasional compounding pharmacists,
attested to by the mortar and pestle that are symbols of pharmacy
practice. These pharmacists help patients who need smaller doses or
different forms or formulations of medications than may be readily
available from manufacturers. Children may need medication in a
different form to use it. If a child cannot swallow a pill, for
example, he or she may need a liquid. Similar considerations apply to
hospice patients who may be unable to receive medication by its
traditional route. Dermatologists often prescribe compounded products
because of the unavailability of certain drug combinations; others are
allergic to dyes and preservatives used in medications they need.
It is vital to preserve this traditional compounding, maintaining
the value provided to patients, but we must make sure manufacturing of
pharmaceuticals is not done under the guise of drug compounding.
Tennessee's laws and regulations, as do most States, provide that
the practice of pharmacy includes compounding. In Tennessee, there is
not a separate license for pharmacies who do drug compounding;
therefore Tennessee regulates pharmacies under its general pharmacy
laws and regulations. It is important to note Tennessee also has a
similar license category that encompasses and regulates manufacturers/
wholesalers/ distributors of drugs. The same regulations apply to out-
of-state pharmacies, although we necessarily must rely upon the
pharmacy's home State and/or Federal entities to inspect and provide
``on the ground'' regulation. There is always room for improvement.
Attention to both regulatory and industry standards are necessary,
complimented by a robust and adequately resourced regulatory effort to
achieve these improvements. We are actively reviewing our own
processes--and in partnership with our Boards, including our Board of
Pharmacy, professional associations and other stakeholders--we are
considering how we can improve our own regulatory posture, efficiency
and effectiveness in Tennessee to assure the safety of patients and the
confidence of our public, as well of the people outside our borders who
rely on us to regulate their suppliers.
We understand in this situation we can be vulnerable to over-
reacting but at the same time we do not want to do too little. Clearly
the status quo is not acceptable. While our State is also a victim of
these bad actors in another jurisdiction, that does not relieve us of
our responsibility to look at our own processes with a critical eye and
make them better. When events like this contaminated medication tragedy
occur or when we identify a ``near miss'' we must take the opportunity
to see how we can prevent a similar event from occurring again. We are
committed to doing just that. In my 15 months as Commissioner of Health
in Tennessee and more than two decades in public health, the need to do
so has never been more clear.
As an example, we acquire information about non-resident
compounding pharmacies from the pharmacy's home State through
reciprocity. We could require more information be provided with respect
to a pharmacy's operation, so we can more readily identify issues which
require investigation or action by State regulators. We also believe
information can be collected that will help draw a distinction between
traditional compounding and mass-compounding pharmacies. Our review of
these issues has led us to believe the factors which the FDA stated it
would consider in determining when it would take enforcement action are
generally appropriate. We believe a regulating body should:
Determine whether the pharmacy is compounding drugs in
response to or anticipation of receiving prescriptions for individual
patients.
Determine whether the pharmacy is compounding drugs that
were withdrawn or removed from the market for safety reasons;
Determine whether the pharmacy is compounding finished
drugs from bulk active ingredients that are not components of FDA
approved drugs;
Determine whether the pharmacy is receiving, storing, or
using drug substances without first obtaining written assurance from
the supplier that each lot of the drug substance was made in an FDA-
registered facility; and for substances intended for sterile
compounding, is sterile upon receipt.
Determine whether the pharmacy is receiving, storing, or
using drug components not guaranteed or otherwise determined to meet
official compendia requirements;
Determine whether the pharmacy is using commercial scale
manufacturing or testing equipment for compounding drug products;
Determine whether the pharmacy is compounding drugs for
third parties who resell to individual patients or offering compounded
drug products at wholesale to other State licensed persons or
commercial entities for resale; and
Determine whether the pharmacy is compounding drug
products that are commercially available or that are essentially copies
of commercially available FDA-approved drug products.
We don't believe any adverse event reporting requirement that
exists will capture every occurrence that could lead to harm.
Additionally, some errors are not easily detected and therefore not
likely to be identified or reported. In the subject outbreak, the
fungal meningitis, was not a reportable disease and may have gone
undetected as an adverse medication event had we not had robust and
trusting relationships with healthcare professionals through our CDC
funded healthcare associated infection team and the astute clinicians
and scientists that identified a concerning occurrence. In this same
case, strokes occurred that were not initially recognized as being
linked to the injection of tainted epidural steroids.
We believe it is important for the Federal Government to respond to
this issue because many drugs are introduced into interstate commerce,
and it is the proper role of the Federal oversight agencies to regulate
these drugs and those producing the drugs. In addition to appropriate
Federal regulation, however, the Tennessee Department of Health would
like to take this opportunity to stress the importance of our State-
Federal partnerships. The capacity building funding for emergency
preparedness and training has ensured our ability to marshal resources,
particularly people and expertise, to respond correctly and rapidly and
to be able to mount a surge of effort in an emergency situation. The
prior existence and availability of those resources and excellent
communication with Federal partners in this outbreak made a significant
difference in the speed and thoroughness of our response. It is crucial
these resources remain available to the States for any such future
event of public health significance.
In summation, the Tennessee Department of Health is supportive of
strengthening the regulatory process for compounding pharmacies through
fact-based initiatives that ensure what happened at New England
Compounding Center will not happen again. Compounding pharmacies have
provided safe, reliable medications for many years, and we shouldn't
allow the aberration of a few to negate the value of many who serve
admirably. We would also note that regulation is necessary but not
sufficient to ensure safe and effective medications. We must also rely
on the professionals who do the work every day to keep their sacred
obligations to the patients and clinicians they serve in the forefront
at all times. We encourage the committee to make sure existing laws and
regulatory practices are rigorously enforced, and to consider any
additional authorities deemed necessary to ensure all Americans that
the drugs they receive through interstate commerce meet all applicable
quality standards including safety and effectiveness.
Thank you for your work in this critical area.
______
State of Tennessee, Department of Health,
Bureau Of Health Licensure and Regulation,
Division of Health Related Boards,
Nashville, TN 37243.
Hon. Lamar Alexander,
U.S. Senate,
Washington, DC 20510.
Senator Alexander: I wanted to thank you for the opportunity to
submit testimony for the upcoming hearings related to compounding
pharmacy. The magnitude of the fungal meningitis outbreak has
reinforced the need to improve regulation of facilities performing high
volume sterile product preparation, both pharmacies and manufacturers.
My answers to the questions posed are delineated below.
Question 1. What is the appropriate role of compounding pharmacies
in providing medicines to patients?
Answer 1. Compounding is a cornerstone of the practice of pharmacy.
Compounding pharmacists prepare custom medicines for patients who may
be allergic to a particular ingredient, require a smaller (or larger)
dose, or need specialized or rare pharmaceuticals. Compounding has
traditionally been limited to these sorts of activities. Compounding
requires a high level of pharmacological expertise, as well as close
coordination with other health care providers and patients. However, in
recent years the practice of compounding has been expanded to include
the large-scale repackaging, mixing, and fabrication of drugs. This
practice, which under certain circumstances could be considered ``drug
manufacturing,'' varies from the traditional practice of compounding. A
complex set of factors has led to the rise of this practice, and it is
therefore difficult to lay the blame at the feet of any party. While
these sorts of organizations have played a valuable role in ensuring
the stability of our drug supply, steps should be taken to ensure the
continued existence of traditional pharmacy compounding.
Question 2. What is Tennessee's experience with licensing,
regulating, and overseeing in-state compounding pharmacies operating
within Tennessee's borders? Out-of-state compounding pharmacies? Are
there areas that need improvement?
Answer 2. Tennessee law recognizes that compounding is an integral
part of the practice of pharmacy. Compounding pharmacies in Tennessee
are regulated under the same standards applied to retail pharmacies;
there are not distinct licenses for each type of practice. Periodic
inspections are carried out by pharmacist investigators to ensure
compliance in all areas of pharmacy practice, including compounding.
Out-of-state compounders are judged by the same standards as out-
of-state retail pharmacies. The same regulations apply to each, but we
have to rely upon regulators in each pharmacy's home State to inspect
and ensure that out-of-state pharmacies comply with the law. It would
not be practical to inspect all out-of-state pharmacies that hold
Tennessee licenses, nor would it be practical to inspect all drug
products shipped into the State from out-of-state pharmacies.
Specific legislation targeted at sterile compounding practices, as
well as legislation or regulation that makes a distinction between
traditional compounders and manufacturers are two areas to consider.
Additional resources could also be helpful.
Question 3. Where do you obtain information about non-resident
compounding pharmacies? What solutions would you recommend to improve
the availability and understanding of that information?
Answer 3. We acquire information about non-resident compounding
pharmacies from regulators in each pharmacy's home State. We could
require that more information be provided with respect to a pharmacy's
operation, so that we could readily see if there are issues which
require investigation or action by State regulators. We could also
increase our cooperation and information sharing with Federal entities
such as FDA and DEA when the regulatory boundaries blend or crossover.
Question 4. Is there a way to draw a distinction between
traditional compounding pharmacies and mass-compounding pharmacies
similar to what NECC was doing?
Answer 4. The FDA uses several factors to differentiate between
traditional compounding and NECC-type operations. These factors are
very helpful in drawing this distinction, and are set out below:
Determine whether the pharmacy is compounding drugs in
anticipation of receiving prescriptions, except in limited quantities;
Determine whether the pharmacy is compounding drugs that
were withdrawn or removed from the market for safety reasons;
Determine whether the pharmacy is compounding finished
drugs from bulk active ingredients that are not components of FDA
approved drugs;
Determine whether the pharmacy is receiving, storing, or
using drug substances without first obtaining written assurance from
the supplier that each lot of the drug substance was made in an FDA-
registered facility;
Determine whether the pharmacy is receiving, storing, or
using drug components not guaranteed or otherwise determined to meet
official compendia requirements;
Determine whether the pharmacy is using commercial scale
manufacturing or testing equipment for compounding drug products;
Determine whether the pharmacy is compounding drugs for
third parties who resell to individual patients or offering compounded
drug products at wholesale to other State licensed persons or
commercial entities for resale; and
Determine whether the pharmacy is compounding drug
products that are commercially available or that are essentially copies
of commercially available FDA-approved drug products.
Question 5. How do Tennessee providers using an out-of-state
compounding pharmacy evaluate and determine to use that pharmacy?
Answer 5. This aspect is part of the practice of medicine in
Tennessee. It is the facility or provider's ultimate choice to pick a
supplier.
Question 6. Do you believe that existing adverse event reporting is
adequate to capture any event that may occur as the result of a
compounded prescription drug?
Answer 6. It is difficult to determine what sort of adverse event
reporting structure could have prevented this tragedy. It is hard to
develop event reporting requirements that cover enough ground, but
aren't overly burdensome to our health care providers. Given the
rapidly changing nature of the healthcare and pharmaceutical
industries, event reporting criteria would likely need to be constantly
updated. While it is important that health care providers report
adverse events to the appropriate bodies, it also ensures that the
regulators have the necessary tools to work with the private sector in
the event of an emergency.
Question 7. Do you think there should be a Federal response to
clarify how compounding pharmacies are regulated in light of the
actions of NECC?
Answer 7. Yes, clarification is highly important as it pertains to
the differentiation between manufacturing and compounding pharmacy and
the resulting variances in regulation. Federal leadership would also be
beneficial to develop communication channels that will increase
transparency and facilitate interstate and interagency information
exchange, resulting in more informed regulation by individual States or
regulating bodies.
Thank you for your willingness to take on the daunting task of
regulatory reform. With thoughtful input from a variety of sources, we
are more likely to find a fitting solution to the challenges that we
face.
Sincerely,
Andrew C. Holt, Pharm.D.,
Executive Director,
Tennessee Board of Pharmacy.
______
Prepared Statement of Craig Becker, President, Tennessee Hospital
Association (THA), Nashville, TN
On behalf of the Tennessee Hospital Association and its member
hospitals, I would like to thank Senator Alexander for the opportunity
to comment on the recent meningitis outbreak in Tennessee and the
impact on the patients we serve. It is my intention to provide the
Health, Education, Labor, and Pensions (HELP) Committee with a
chronological description of events, the role of THA and finally with
lessons learned from this tragedy.
First and foremost, THA and its members' primary concern is over
the health of the patients impacted by this tragedy. Once the problem
had been identified by the Tennessee Department of Health (TDH) and the
Center for Disease Control (CDC), THA members stopped using the tainted
product. Once the cause of the outbreak and a course of action had been
determined, THA and its members took every appropriate action to deal
with this unprecedented crisis.
We hope and pray that there never will be another incident like
this, but we feel the systems in place to notify members, pull the
tainted product off the shelves and treat the infected patients,
worked. We cannot thank enough the TDH, Commissioner John Dreyzehner,
M.D., MPH, Marion Kainer, M.D., MPH, Director, Healthcare Associated
Infections and Antimicrobial Resistance program and the rest of the TDH
staff for its prompt actions and for its succinct directions to the
provider community.
THA's role in this event was primarily to act as a conduit for
information to our members and non-members alike, as it was made
available from the TDH and other Federal agencies. THA has a data base
of all key administrative and clinical people in Tennessee's hospitals.
At various times, at the direction of the TDH, THA provided hospitals,
both members and non-members, with critical information about the
crisis and more important, actionable directions on how to treat, or
not treat those affected patients.
chronology
I believe it would be instructional for the committee to know the
chronology of events THA has developed from our combined notes and
calendars. It should be understood this is based on THA material and
not others, who may differ with our view.
September 18, 2012--Dr. April Pettit, an infectious disease
specialist at Vanderbilt University Medical Center, treats the first
(index) case, realizing this type of spinal meningitis was extremely
rare. Dr. Pettit alerted TDH to the potential problem. Dr. Kainer
immediately implements surveillance procedures to determine if there
were other cases.
September 20, 2012--TDH identifies two other possible cases. Dr.
Kainer notifies CDC.
September 24, 2012--After surveying the clinic where the outbreak
had occurred, TDH traces tainted product back to New England
Compounding Center (NECC) and requests from Massachusetts Department of
Health (MDH) a distribution list of all products shipped to Tennessee.
September 25, 2012--Tracing records back, TDH determines ``Clinic
A'' as the likely location for several of the patients. It should be
noted that the provider community acted immediately, closing the
suspected clinic and totally supported the TDH investigation. The
clinic identified and gave all patient information to TDH and provided
full access to clinical records.
September 26, 2012--NECC issues a voluntary recall of steroid
products.
September 28, 2012--CDC declares the problem a multi-state
outbreak.
October 30, 2012--At the direction of Commissioner Dreyzehner, THA
began acting as a conduit of information to get information to all key
staff in hospitals and clinics, noting the clear connection to NECC.
October 5, 2012--Federal Drug Administration (FDA) confirms a
sealed vial is contaminated and issues a national recall and order to
cease using NECC products.
October 8-10, 2012--THA and TDH work together providing constant
timely information to providers on findings and treatment
recommendations.
October 15, 2012--THA hosts a conference call with TDH and key
hospital staff.
October 16, 2012--THA staff follows up with personal calls to same
key staff of all hospitals and clinics that received NECC product to be
sure the product has been pulled from all clinical areas, including
crash carts, ambulatory units, etc.
October 17, 2012--THA briefs FDA on the situation and requests
guidance on who our providers should contact, what they should say,
what patient prioritization (surgery, topical, etc.) should providers
use, and guidance on how to deal with the pediatric population. FDA
took our request under advisement.
October 18, 2012--THA, working with TDH, sends out sample
notification letters, which includes guidance from FDA and CDC. Again,
THA personally contacts those impacted hospitals and clinics.
October 19, 2012--THA provides additional information received from
TDH on media responses, patient letters. This became a burden for
hospitals not NECC. Also, a flood of ``worried well'' patients began
showing up in hospital ERs. Hospitals had to take critical staff away
from patient care to staff call centers to field calls from the
``worried well.''
October 20, 2012--To present TDH determines 42 days is the critical
time for incubation of the disease, and flood of patients begins to
ease. THA and TDH continue to be in constant contact and alerts are
sent as needed.
lessons learned
As in any crisis, it is always important to review lessons learned
to be prepared for the future disaster. The following represent the
significant findings from THA's perspective.
1. The Tennessee Health Alert Network, (THAN), developed after 9/11
was invaluable. Even with THA having an extensive list of key staff,
THAN alerted providers about the problem much faster than we could have
otherwise.
2. Having a transparent and open line of communication with TDH,
THA and the provider community was the most important element of
dealing with the crisis. Drs. Dreyzehner and Kainer are to be commended
for keeping in constant contact and for being willing to utilize a non-
government entity such as THA to transmit accurate and timely
information. We found it discouraging that Federal agencies weren't
aware of the role non-governmental entities could play in such an
emergency.
3. There needs to be a better system of contacting smaller
ambulatory care and physician office settings. Getting the information
to them was mostly through the media.
4. Better and timelier guidance from Federal agencies is critical.
There were many questions around whether or not products such as eye
drops should be given priority status and what providers should tell
patients. It appeared to those of us in the field that coordination
among agencies was lacking. One suggestion would be to designate a lead
agency in a crisis like this and to empower the appropriate staffs to
give out information to providers and their representatives instead of
having to ``run it up the flag pole.''
5. As a follow up to No. 4, a national spokesperson speaking out on
the crisis would have been very helpful. In Tennessee, Dr. Dreyzehner
was the very effective face of the crisis. He was transparent, open and
didn't avoid the tough questions.
6. This was a supplier issue, not a provider issue. Hospitals,
doctors and nurses worked on the assumption these drugs were safe;
however when the crisis erupted, it became their problem, not NECC's.
It would have been helpful for a Federal agency to make it clear to the
public that it was NECC's problem, not the provider community. In some
ways, our doctors and nurses feel as much a victim as our patients.
conclusion
This was a tragedy to our patients, to the trust in the safety of
our drugs from both the provider and patient perspective and to the
providers who injected what they thought was safe product. I have
personally talked with doctors and nurses who have said they are
devastated by what happened.
Again, I cannot express enough appreciation to Drs. Dreyzehner and
Kainer and the entire TDH staff for its support, quick action and
openness, all of which no doubt saved lives. We have learned from this
tragedy and will be better prepared for the next one. It is our
greatest hope that hospitals, doctors and nurses can be assured we have
safe and adequate medications, to serve the American people.
Thank you for your time and for allowing me to thank those who
acted so courageously in dealing with this outbreak.
______
Tennessee Pharmacists Association (TPA),
Nashville, TN 37219,
November 15, 2012.
Hon. Lamar Alexander,
U.S. Senate,
455 Dirksen Senate Office Building,
Washington, DC 20510.
Re: Response to Request for Testimony Regarding Pharmacy Compounding in
Tennessee
Dear Senator Alexander: The Tennessee Pharmacists Association
appreciates the opportunity to submit testimony for the record to the
U.S. Senate Health, Education, Labor, and Pensions (HELP) Committee for
your November 15, 2012, hearing entitled ``Pharmacy Compounding:
Implications of the 2012 Meningitis Outbreak.'' We thank you for your
service to the citizens of Tennessee and our country.
The Tennessee Pharmacists Association (TPA) is a professional
organization representing pharmacists, student pharmacists, pharmacy
technicians and others interested in improving medication use and
patient care in Tennessee. TPA members provide care in all practice
settings, including community pharmacies, hospitals, long-term care
facilities and other settings. TPA and its members are deeply concerned
about the tragic situation that has occurred as a result of what
appears to be large-scale manufacturing by a pharmacy in Massachusetts,
and we are prepared to work with legislators and regulators to assure
public safety and access to quality medications that meet patients'
needs. We extend our deepest sympathy to patients and families affected
by this tragic event.
responses to specific questions
The questions you posed demonstrate a sincere desire to understand
the complexities of the issue, and Tennessee's pharmacists appreciate
your commitment. Our responses are provided after surveying TPA member
pharmacists and reviewing their responses to the questions. In some
instances, responses are provided that are specific to hospital/health-
system pharmacy practice settings and are so noted.
To assure a clear understanding of the answers below, we are
providing the definitions for ``compounding'' and ``manufacturer''
found in the Tennessee Pharmacy Practice Act, TCA 63-10-204:
Compounding
(4) ``Compounding'' means the preparation, mixing, assembling,
packaging or labeling of a drug or device:
(A) As the result of a prescription order or initiative based
on the prescriber-patient-pharmacist relationship in the course of
professional practice,
(B) In anticipation of prescription orders based on routine,
regularly observed prescribing patterns; or
(C) For the purpose of, or as an incident to, research,
teaching or chemical analysis and not for sale or dispensing;
Manufacturer
(21) ``Manufacturer'' means any person, except a pharmacist
compounding in the normal course of professional practice, engaged in
the commercial production, preparation, propagation, conversion or
processing of a drug, either directly or indirectly, by extraction from
substances of natural origin or independently by means of chemical
synthesis, or both, and includes any packaging or repackaging of a drug
or the labeling or relabeling of its container and the promotion and
marketing of such drugs or devices;
Question 1. What is the appropriate role of compounding pharmacies
in providing medicines to patients?
Answer 1. Compounding has been and continues to be an essential and
integral part of the profession of pharmacy and was the major component
of pharmacy practice for many years prior to large-scale pharmaceutical
manufacturing. Compounding allows pharmacists to meet specific patient
medication needs, including veterinary needs. Pharmacists are educated,
trained and qualified to provide these services for their patients.
Generally speaking, compounding of a pharmaceutical product occurs
when a particular patient has a specific need and the medication dosage
form or concentration required to treat that need is not available from
a commercial manufacturer, or is not available due to a shortage. Many
patient populations require medications that may not be available for a
variety of reasons. For example:
1. Pediatric patients, particularly neonates, may require small
dosages or customized dosage forms that aren't manufactured by an FDA-
approved manufacturer.
2. Geriatric patients may need a dose in an oral liquid that can be
administered via nasogastric tubes.
3. Patients undergoing anesthesia, such as women in labor, require
medications that must be sterile and free of preservatives in order to
be safely administered through an epidural injection.
Increasingly, compounded pharmacy products are also purchased to
fulfill patient needs for prescription drugs that are not available due
to manufacturers' shortages or back-order situations. When certain drug
products cannot be purchased through the routine inventory chains, the
critical product may only be available through compounding pharmacies.
Critical shortages continue to contribute to medication safety issues,
and compounding pharmacies are often the only source of these agents.
Compounding is a necessary component of the professional practice
of all pharmacies. Many community pharmacies routinely engage in
preparation of non-sterile pharmaceuticals. The simple mixing of two
commercially manufactured products into a new product--such as adding a
customized flavoring agent--is compounding, as is mixing two creams
together. Preparing of any intravenous admixture or creating specialty
pediatric or geriatric dose formulations is also compounding, in that a
manufactured product is altered for specific patient needs. All
pharmacists must have the right to compound and prepare a product for
an individual patient need.
Additional Comments From the Health-System/Hospital Pharmacy Community
While not every community pharmacy is equipped for sterile
compounding, it is a necessary component in the daily routine of every
hospital pharmacy. Compounding pharmacies provide a significant service
to hospital patients. They formulate therapeutic and diagnostic
products, make noncommercial formulations, customized preservative-free
and dye-free formulations, and are essential to meet the needs created
by national pharmaceutical shortages. Compounding pharmacies fill a
niche with high-risk compounding, such as non-sterile to sterile IV
admixtures like cardioplegia solutions or IV Continuous Renal
Replacement Therapy solutions. Most inpatient hospital pharmacies in
Tennessee do not have IV rooms that meet structural USP 797
regulations, nor the equipment, expertise, or testing processes to
perform this level of compounding safely. Compounding pharmacies can
provide this service at an extremely high quality. With the critical
shortages of sterile injectibles, especially medications that are used
in code or emergency situations, compounding pharmacies also perform
sterile transfer from larger size injectibles to the size and dosage
form that is readily available. This prevents serious medication errors
from occurring and prevents delays in emergency therapy.
Question 2. What is Tennessee's experience with licensing,
regulating, and overseeing in-state compounding pharmacies operating
within Tennessee's borders? Out-of-state compounding pharmacies? Are
there areas that need improvement?
Answer 2. The Tennessee Board of Pharmacy has successfully
regulated all pharmacies providing patient care services in Tennessee,
including both hospital- and community-based pharmacies that compound.
Additionally, the Board of Pharmacy regulates manufacturers,
wholesalers and distributors located in Tennessee. State law requires
all Tennessee Board of Pharmacy investigators to be pharmacists
licensed in Tennessee. The Tennessee Board of Pharmacy routinely
inspects all licensees located in-state to verify compliance with laws,
rules and standards of practice.
Tennessee law requires any pharmacy, regardless of whether located
in-state or out-of-state, providing services to a Tennessee resident to
be licensed by the Tennessee Board of Pharmacy. Regarding out-of-state
pharmacies, the Tennessee Board of Pharmacy relies on the Boards of
Pharmacy in other States for regulation of the pharmacies in their
respective States. The Tennessee Board does not and cannot conduct on-
site inspections of out-of-state pharmacies to verify compliance with
Tennessee law and Board regulations. Inspections by out-of-state
agencies, if conducted at all, may vary widely from State to State, as
do State rules and regulations. The qualifications of the inspectors in
other States may vary as well.
Inspections of pharmacies by qualified personnel are critical.
Visual, on-site inspection of the premises, the culture of the pharmacy
staff, and operations are important in assessing the appropriate
actions of the pharmacy being inspected. We believe all States must
have requirements for routine and thorough inspections of pharmacies.
It is imperative that all Boards of Pharmacy be provided sufficient
resources to employ optimal numbers of pharmacists as inspectors and to
provide the ongoing training needed by those pharmacist inspectors.
Question 3. Where do you obtain information about non-resident
compounding pharmacies? What solutions would you recommend to improve
the availability and understanding of that information?
Answer 3. From a regulatory perspective, information on non-
resident compounding pharmacies comes from the Tennessee Board of
Pharmacy or, if information is shared, from the Board of Pharmacy in
the State where the pharmacy is originally licensed.
Most information regarding sources of compounded products comes
either from hospital pharmacy buying groups or as ``word of mouth'' or
recommendations from colleagues. Marketing materials or advertisements
may also be a source of information. Small hospitals would rely heavily
on such materials, while larger institutions with greater resources at
their disposal may conduct on-site visits at out-of-state pharmacies.
Question 4. Is there a way to draw a distinction between
traditional compounding pharmacies and mass-compounding pharmacies
similar to what NECC allegedly was doing?
Answer 4. It is very difficult to definitively differentiate
between compounding and manufacturing in all circumstances. While it is
easy to determine that a traditional pharmacy practice providing
patient-specific, small-volume services as described in the definition
of compounding is ``compounding,'' the provision of compounded
medications may be of significant volumes and still be compounding as
opposed to manufacturing. Manufacturing occurs when individual patient
needs are not part of the process. Altering drug products in large
quantities for resale that are not prepared and labeled for specific
patient use in the final State is manufacturing. Current State and
national laws need to be enforced to protect our citizens.
Whatever proposals are considered, we believe it is important that
State Boards of Pharmacy continue to license and regulate traditional
compounding, while recognizing that large-scale production of sterile
products that are not for specific patients may require oversight by
the Food and Drug Administration (FDA) in cooperation with State Boards
of Pharmacy. A process for better collaboration and cooperation between
State Boards of Pharmacy and the FDA would be a step forward.
Question 5. How do Tennessee providers using an out-of-state
compounding pharmacy evaluate and determine to use that pharmacy?
Answer 5. The Tennessee Department of Health has an on-line
resource that allows healthcare providers to research the licensure of
all entities through a web portal: http://health.state.tn.us/HCF/
Facilities_Listings/facilities.htm.
Pharmacists also use an evaluation tool published by the American
Society of Health-System Pharmacists. This tool can be located at:
http://www.ashpfoundation
.org/sterileproductstool.
In addition, pharmacists receive information through hospital
buying groups and from marketing information received. Again, word of
mouth or positive recommendations by colleagues can have a major
influence on selection of out-of-state compounding pharmacies.
Availability and pricing may be considered in these decisions.
Question 6. Do you believe that existing adverse event reporting is
adequate to capture any that may occur as the result of a compounded
prescription drug?
Answer 6. The Tennessee Board of Pharmacy rule 1140-03-.14(14)
states:
``The designated pharmacist in charge shall report to the
board any situation in which a medical or prescription order
has caused serious personal injury or death.''
In Tennessee, reporting of adverse events that occur at this level is
not an option but a requirement.
The current national system of voluntary reporting adverse
medication reactions is probably underutilized for both compounded and
manufactured medications. While pharmacists support the concept of
actively reporting adverse reactions to compounded and commercially
available preparations, the existing system--FDA MedWatch program--is
designed in such a manner as to actually impede pharmacists'
participation. There needs to be additional collaboration between the
FDA and compounding pharmacists, so this system can be widely and
meaningfully used.
Additional Comments From the Health-System/Hospital Pharmacy Community
The existing FDA adverse event reporting mechanism commonly
referred to as MedWatch (https://www.accessdata.fda.gov/scripts/
medwatch/medwatch-online.htm) is cumbersome and time-consuming.
Furthermore, it is an entirely voluntary process. We believe that the
vast majority of providers/prescribers are unaware of this reporting
process. We also believe that many reports are never made due to a fear
of reprisal.
Question 7. Do you think there should be a Federal response to
clarify how compounding pharmacies are regulated in light of other
actions of NECC?
Answer 7. We believe that if NECC had been properly categorized as
a manufacturer (instead of a compounding pharmacy), existing
regulations as enforced by the FDA would have been adequate to prevent
this tragedy from taking place. We believe there is a need for more
stringent oversight and a clearer distinction between compounding and
manufacturing. The FDA does require clear authority, adequate funding
and staffing in order to properly inspect and oversee manufacturers of
pharmaceuticals.
Unfortunately, there are no laws that will absolutely prevent
unethical behavior or operations that fall short of recognized
standards. Thorough and routine inspections by qualified and trained
individuals and stringent oversight by regulatory personnel are the
best approaches to prevent these types of situations.
TPA remains committed to working with Congress, State legislators,
national and State regulators, and other stakeholders to address any
regulatory gaps that may exist and reduce the likelihood of any
problems from compounded products in the future.
Please contact me if you have questions or need additional
information regarding the comments that TPA has submitted. Again, thank
you for requesting input from pharmacists and other health care
professionals in Tennessee.
Sincerely,
Baeteena M. Black, D.Ph.,
Executive Director.
______
Tennessee Medical Association (TMA),
Nashville, TN 37212,
November 14, 2012.
Hon. Lamar Alexander,
U.S. Senate,
455 Dirksen Senate Office Building,
Washington DC 20510.
Re: Meningitis Outbreak
Dear Senator Alexander: Thank you for the opportunity to make
comments on the recent nationwide meningitis outbreak. First and
foremost, our hearts go out to the thousands of patients who sought
care from physicians for chronic back pain, only to later learn that
the medication administered was contaminated. Whether the patients were
diagnosed with fungal meningitis or were fortunate enough not to be
affected, they all were placed in an unfortunate position that was
probably preventable had there been more oversight of the Massachusetts
compounding pharmacy.
For background purposes, members of the Senate Health, Education,
Labor, and Pensions Committee should be aware that chronic pain and its
treatment has become an increasingly visible part of medical treatment
over the last 20 years. Well-educated and appropriately trained
physicians will almost always initiate other, less aggressive forms of
treatment, such as pharmaceutical or physical therapy, before
initiating spinal injections or even more invasive surgical procedures.
A provider treating chronic back pain should be somewhat passive when
starting spinal injections and, if the patient does not get relief,
stop the treatment regimen.
Compounding pharmacies, both local to the State of Tennessee and
those that are external to the State of Tennessee doing business in our
State, are overseen and licensed by the Tennessee Board of Pharmacy.
Tennessee physicians believe that our Pharmacy Board performs these
duties with great care and diligence. We have no reason to believe that
any patient seen and cared for at any of the three centers which
received the tainted medication here in Tennessee was provided anything
but the appropriate standard of care. Our pain physicians in the State
tell us that they do use compounded drugs for those hard to get drugs
or for repackaging. Prior to this outbreak, the prevailing perception
among the physician community in Tennessee was that compounding
pharmacies were as regulated as manufacturing pharmacies and that
generally the products they marketed met the necessary quality control
standards for safety and efficacy.
We now know differently and believe that Congress can assure the
development of a transparent and accountable regulatory system, whether
that be Federal or on a State level, over the production and
distribution of compounded drugs. It is our understanding that, if the
company had been licensed as a manufacturer, they would have come under
the aegis of the FDA. Regulatory gaps should be filled so physicians
can once again feel safe about the compounded drugs they order. Should
Congress determine that the Food and Drug Administration is the proper
entity to oversee this facet of the health care system, we would ask
you to provide the agency with the necessary authority and resources to
effectively regulate the industry.
In terms of the adverse event reporting, existing mechanisms are in
place to report adverse outcomes. The elusive component of any
reporting system is ``recognizing'' an event as adverse and related to
a medication, compounded or not. Fortunately, a very perceptive
Vanderbilt physician was able to identify the cause of a very bad
outcome and reported it immediately to State officials. Once
recognized, capturing and reporting is reasonably straight-forward.
Since the outbreak was publicized, we have heard from some
individual physicians specializing in pain care that patients have
expressed a real reluctance to undertake spinal injections. For some,
other treatment options may be available but for many the injections
represent the best long-term hope for relief of their pain. Although
their reluctance is certainly understandable, such a response limits
the options available to the treating physician and ultimately will
mean less-than-acceptable care to the patient. Whatever Congress can do
to assure consumers that this outbreak represents an opportunity to
make real change that will minimize the possibility of future
reoccurrences would be a significant step forward.
Thank you again for the opportunity to make comments on this issue.
Sincerely,
Wiley Robinson, M.D., FHM,
President.
______
The Commonwealth of Massachusetts,
Boston, MA 02108-4619,
January 23, 2013.
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Attn: Pamela J. Smith, Staff Director; and
Frank J. Macchiarola, Republican Staff Director,
428 Senate Dirksen Office Building,
Washington, DC 20510-6300.
Dear Ms. Smith and Mr. Macchiarola: Thank you for the opportunity
to respond to your member's inquiries regarding compounding pharmacy
oversight and the New England Compounding Center (NECC)--the company
primarily responsible for the meningitis outbreak that has claimed
dozens of lives across the country. As the Massachusetts Department of
Public Health continues to take aggressive actions to protect public
safety, our ongoing collaboration with your committee is important to
ensure that this type of tragedy never happens again.
In Massachusetts, we have taken significant actions to enhance our
regulations, increase inspection schedules and hold pharmacies
accountable following this tragic outbreak. And this month, Governor
Patrick filed strong legislation to further increase oversight of
pharmacies, including regulation of out-of-state pharmacies and
reconstitution of our Board of Pharmacy. As we work to raise standards
in Massachusetts, we urge Congress to act to strengthen Federal
oversight to address the regulatory grey areas that exist between State
and Federal regulation.
The Department is committed to our continued and close
collaboration with the committee, the Centers for Disease Control and
Prevention (CDC), the U.S. Food and Drug Administration (FDA), and
other States' public health officials to investigate the exact cause of
an outbreak to take the necessary actions to enhance policies and adopt
best practices both here and across the Nation.
I welcome the opportunity to continue this work with you, your
fellow committee members, and the U.S. House Energy and Commerce
Committee to address these critical needs.
Below you will find answers to your specific questions. Please do
not hesitate to be in touch with me or my staff. We thank you for your
continued leadership.
Sincerely,
Lauren A. Smith, M.D., MPH,
Interim Commissioner.
______
Question 1. Why did the Massachusetts Board of Pharmacy enter into
a weakened consent agreement with NECC, even after forwarding the
original, stronger consent agreement (which included a public
reprimand) to the prosecuting attorneys within the Department of Public
Health?
Answer 1. These actions were taken in 2006 during a previous
Administration and are deeply troubling. An extensive file-by-file and
e-mail review conducted by staff has yet to uncover any documentation,
information or communications that clearly describe what transpired
between the initial consent decree in 2004 and the final actions taken
by the Board in 2006.
While NECC bears the primary responsibility for this tragic
outbreak, it is apparent that Board staff displayed poor judgment,
missed opportunities and failed to take appropriate action to hold NECC
accountable. Those individuals who were responsible have been removed
from their jobs.
Question 2. Did the Department of Public Health ever consider legal
action as an alternative to either of the consent agreements?
Answer 2. As stated above, the lack of documentation related to
these decisions is troubling. In the absence of such information, we
cannot clearly establish the array of options that may have been
considered.
Question 3. What steps are you currently undertaking to improve
oversight of compounding pharmacies in Massachusetts?
Answer 3. Following my testimony before the committee on November
15, 2012, the Commonwealth has taken significant actions to this
effect, which I am happy to share with you.
We advanced emergency regulations that went into effect immediately
on November 1, 2012, to enhance our ability to monitor the sterile
compounding industry. The new regulations require sterile compounding
pharmacies in Massachusetts to report, for the first time, volume and
distribution figures to the State, which will alert the Board of any
pharmacy that is acting like a manufacturer, which requires an FDA
license.
The regulations also require all licensed pharmacies and
pharmacists to report to the Board when they are the subject of any
disciplinary action by any State or Federal agency. This will allow the
Board to know when other entities have identified issues with
Massachusetts-licensed pharmacies.\1\
---------------------------------------------------------------------------
\1\ Please note that the Massachusetts Board of Pharmacy voted on
final regulations as described on January 8, 2013. These regulations
will become final once published within the Massachusetts Register on
February 1, 2013.
---------------------------------------------------------------------------
Nearly 40 pharmacies have been inspected since Governor Patrick
directed the Board of Pharmacy to begin checks of compounding
pharmacies that produce sterile injectable medications. These
inspections identified problems in several pharmacies for which new
cease and desist orders have been issued and corrective plans have been
put into place.
Other pharmacies that have been inspected have come back with minor
deficiencies that have since been corrected, or are currently being
addressed. Unannounced inspections of compounding pharmacies that
produce sterile injectable medications will continue until all have
been inspected.
We also announced changes at the Massachusetts Board of Pharmacy,
with three new members who work across diverse health care settings
filling seats on the Board.
In October 2012, the Governor established a Special Commission on
Pharmacy Compounding as part of the Administration's comprehensive
response to the outbreak. The Commission met regularly, looking at best
practices in other States and exploring changes to the law to help
address the regulatory gray area surrounding compounding pharmacies. A
final report was issued on January 4, 2013.
Building on the recommendations identified by the Commission, on
January 4, 2013 Governor Patrick also announced the filing of
legislation to reform the Board of Pharmacy and strengthen the
Commonwealth's oversight of the compounding pharmacy industry in
Massachusetts. Specifically, the legislation:
1. Requires a special license for sterile compounding that will
enable regulators to better track and hold pharmacies accountable for
their practices;
2. For the first time, authorizes the Board to assess fines against
Massachusetts-licensed pharmacies that violate Board of Pharmacy
policies, regulations, or statute; and establishes whistleblower
protections for pharmacists and pharmacy staff;
3. Requires licensure for out-of-state pharmacies that deliver and
dispense medications in the Commonwealth;
4. Establishes a clear process to restructure and reorganize the
composition of the Board of Pharmacy, ensuring more balanced
representation of background of Board members to improve oversight of
the industry. The Board will include more members not practicing in the
industry they are responsible for regulating. Under the legislation,
the eleven (11) member Board would be comprised of four pharmacists,
one pharmacy technician, one nurse, one physician, one quality
improvement expert, and three public members who have experience in
healthcare delivery or consumer advocacy.
Question 4. FDA inspectors released recently a report last week
from their recent investigation of Ameridose--a company owned and
managed by the same families as the New England Compounding Center.
This report included the following description of the conditions they
found--I quote:
`` . . . insects were observed to be located in the
unclassified area where finished sterile product is packaged
and stored. The insects were also located within approximately
3 to 10 feet of the controlled area where sterile products are
manufactured. At least one bird was observed flying in the
unclassified area where sterile finished product is packaged
and stored.''
How do you explain the fact that Ameridose was shipping products
all over the country that had been manufactured under these
circumstances, given the years of complaints about both the New England
Compounding Center and Ameridose?
Answer 4. In the course of its licensure in Massachusetts,
Ameridose had been subject to one complaint, pertaining to potential
patent infringement. This issue was settled between Ameridose and the
complainant.
During previous licensure inspections, Board staff did not identify
any findings similar as those witnessed during the joint inspection
with the FDA. As soon as we learned of these issues, we took action to
suspend operations at Ameridose and NECC's other sister companies. The
FDA secured a recall of all Ameridose products and the company remains
closed.
These events have clearly indicated that the complaints-driven
inspection policies that were used by Massachusetts and continue to be
used by many States are insufficient to provide comprehensive oversight
to compounding pharmacies. It is important to know how a pharmacy is
operating when they are not scheduled for an inspection. That is why
Massachusetts now has unannounced inspections of all pharmacies
compounding sterile injectable substances and we have advanced new
regulations to enhance our inspection schedules.
Question 5. Many State Boards of Pharmacy rely on the Board of
Pharmacy in the State where a pharmacy is physically located to conduct
inspections, since most Boards of Pharmacy do not have the capacity to
inspect pharmacies across the country. Given the current crisis, how do
you think Minnesota's Board of Pharmacy can make sure that a pharmacy
in Massachusetts is shipping safe products into Minnesota? Does the
current system work?
Answer 5. As you have pointed out, limited, geographic-bound
resources require greater, more consistent and streamlined
communications between States, as well as our Federal partners.
Although we have taken great strides to increase oversight in
Massachusetts, similar progress is needed at the Federal level. The
Federal Government's role in oversight of interstate commerce is
essential to our shared success. Likewise, the FDA must fulfill its
obligation to ensure that manufacturers declare themselves as such and
abide by all Federal laws and regulations. In Massachusetts, our Board
of Pharmacy has adopted emergency regulations that require every
pharmacy to report within 7 business days all adverse events relating
to the preparation of medications in that pharmacy. Additionally,
pharmacies in Massachusetts are now required to share all disciplinary
actions taken by other States and the FDA on receipt. While this does
not substitute for clear, regular and streamlined communications
between all parties, I believe these to be important steps forward to
ensure this never is allowed to happen again.
As outlined in the Department's response to Question 3, through the
Governor's filed legislative reform, the Board will now have the
authority to regulate out-of-state compounding pharmacies that ship
medications into Massachusetts through the development of an out-of-
state oversight process. The Board will also gain the authority to
create an alternate licensure category for pharmacies that pose a
higher risk to the public, and to levy fines against these licensees
where appropriate. Additionally, Massachusetts is working with our
Commission on compounding pharmacies as well as the National
Association of Boards of Pharmacy (NABP) to further address these
issues and make enhancements where necessary.
Question 6a. In addition to the report from the FDA of infestations
of insects, vermin, and even a bird in Ameridose's facility, according
to the FDA's inspection report, Ameridose did not adequately test
sterility or log complaints from patients and reports of adverse
events. Can you clarify the requirements of a compounding pharmacy in
the Commonwealth of Massachusetts regarding sterility testing and the
reporting of complaints and adverse health events?
Answer 6a. The Massachusetts Board of Pharmacy regulation 247 CMR
9.01(3) requires that ``a pharmacist shall observe the standards of the
current United States Pharmacopoeia.'' Briefly, United States
Pharmacopoeia (``USP'') requires the following testing:
Viable particle testing must be done every 6 months at a
minimum and when certifying new equipment, following any servicing of
facilities or equipment, and in response to issues of compounded
sterile preparations (CSPs).
Sampling of compounding personnel glove fingertips, at
least annually.
Media fill test, at least annually.
All high-risk level CSPs that are prepared in groups of
more than 25 identical single dose packages or multi-dose vials must
meet sterility tests before they are dispensed/administered. (They also
have to be tested for bacterial; endotoxins (pyrogens)).
Additionally, the emergency regulation, 247 CMR 6.15(5), adopted on
November 1, 2012 requires pharmacies to attest to compliance with USP
<797>. In the Spring of 2012, the Board began requiring new pharmacies
that engage in sterile compounding to complete a USP <797> Gap
Analysis. Presently, inspections of pharmacies engaged in sterile
compounding focus on compliance with USP <797>.
The emergency regulation, 247 CMR 6.15(6), adopted on November 1,
2012, requires every pharmacy to report within 7 business days all
errors that occur during the preparation of medications in that
pharmacy, building on previously established reporting requirements for
medication errors that led to patient harm.
Question 6b. Had these requirements been fully implemented, would
they have been sufficient? Does the State have the capacity to enforce
these requirements?
Answer 6b. Massachusetts has the authority to enforce its
regulations, which require compliance with USP <797> and reporting of
adverse events, and to impose disciplinary action for any violation of
its regulations. 247 CMR 6.15(5);247 CMR 9.01(3); 247 CMR 10.03.
Question 6c. Does the State have the capacity to enforce these
requirements for compounding pharmacies located in other States that
are shipping into Massachusetts--for example, the statewide requirement
that Minnesota also has on the books that sterile products be
compounded according to the United States Pharmacopea?
Answer 6c. The Governor's proposed legislation introduces an out-
of-state licensure category, currently not in existence in
Massachusetts. Through comprehensive requirements on all pharmacies
that seek to ship medications to the Commonwealth, we will gain the
authority to enforce requirements in the quality and safety of
compounding processes.
Question 7. After reviewing the documents and looking at the
timeline, it is clear that NECC had multiple violations of
Massachusetts pharmacy law. What, in addition to the multiple
violations and inspection reports, would prompt the Board to suspend or
revoke a pharmacy license?
Answer 7. Under my leadership, the Board and DPH will continue to
act swiftly to hold pharmacies and pharmacists sufficiently responsible
for their actions. While I was not at the Department during the
deliberations around NECC's 2006 consent agreement, it is my position
that the action was insufficient given the severity and volume of
deficiencies from their initial licensure in 1998 through 2004. Since
we learned of this crisis, we secured suspension of operations at NECC
and its sister companies and launched unannounced inspections of all
pharmacies compounding sterile injectible substances, which have also
resulted in additional cease and desist orders and corrective plans.
Question 8. How often do you suspend or revoke licenses, and what
factors are considered when deciding between different disciplinary
actions? What is the process to suspend or revoke a license, both when
you have the consent of the company and you do not?
Answer 8. Inspections and resulting disciplinary actions by the
Board, including but not limited to suspensions and revocations of a
pharmacy's retail license, constitute a complaint-driven process. As
defined with the Board of Pharmacy, a ``complaint'' is a formal
proceeding and does not refer to the colloquial use of the word. The
Board receives approximately 300 complaints per year. The Board opens a
``complaint'' after receiving information about issues with a licensee,
and establishing that an investigation is warranted.
Complaints that warrant disciplinary action are often a result of
identified deficiencies found in the course of an inspection.
Historical data is readily available for the 6 years of the Patrick-
Murray Administration (January 2007 through December 2012). During this
time period, the Board identified deficiencies during its inspections
of the self-identified sterile compounding pharmacies on eight
occasions. In seven of these instances, the deficiencies were resolved
without the need for further Board action; however, Board action was
required in one case. (See CIVAS complaint history, appended and
referenced as Attachment A.) While Attachment A provides a thorough
summary of the history, below are examples of types of deficiencies
noted:
Failures to maintain required documentation (e.g.,
perpetual inventory for controlled substances);
Unregistered technician observed working in control room;
Failure to maintain appropriate supervisory ratios;
Equipment lacking and having outdated seals and/or
certification (e.g., balance);
Broken equipment (e.g., thermometer in ante room);
General concerns regarding cleanliness;
Refrigeration concerns (e.g., refrigeration logs with
temperature readings below recommended level);
Expired drugs on shelves; and
Inadequate security (e.g., door left ajar).
Should a complaint warrant Board action, the Board can choose to
take either a disciplinary or non-disciplinary action. The
Massachusetts General Laws grant the Board the authority to take
various disciplinary and non-disciplinary actions. Disciplinary actions
are intended for those described in our regulations that result in a
permanent mark on a licensee's record that is publicly reported and
available to consumers on our Web site. Disciplinary actions may
include: suspension, revocation of personal registration, pharmacy
permit, license or controlled substance registration, reprimand or
censure of the registrant or licensee, cease and desist notice, consent
agreement or probation. Non-disciplinary actions may include a non-
disciplinary warning letter, advisory letter, a consent agreement with
non-disciplinary actions, or dismissal of the complaint. The actions
available to the Board are summarized with the corresponding statutory
authority (See Attachment B). It should be noted that Governor
Patrick's recently filed legislation authorizes the Board to assess
fines against Massachusetts-licensed pharmacies that violate Board of
Pharmacy policies, regulations, or statute.
From 2002-12, the Board recorded sixty-eight (68) disciplinary
actions taken against Massachusetts retail pharmacies:
Year 2002--No. of Disciplinary Actions: 1
Year 2003--No. of Disciplinary Actions: 4
Year 2004--No. of Disciplinary Actions: 2
Year 2005--No. of Disciplinary Actions: 4
Year 2006--No. of Disciplinary Actions: 2
Year 2007--No. of Disciplinary Actions: 4
Year 2008--No. of Disciplinary Actions: 9
Year 2009--No. of Disciplinary Actions: 9
Year 2010--No. of Disciplinary Actions: 11
Year 2011--No. of Disciplinary Actions: 17
Year 2012--No. of Disciplinary Actions: 5
Question 9. Please briefly discuss past situations in which the
Board has revoked a license. What violations were evident in those
facilities? Was the revocation communicated to other State boards or
the FDA?
Specifically, were any revoked for violations of the patient-
specific prescription rule? What were the circumstances?
Answer 9. Since January 1, 2000, the Massachusetts Board of
Pharmacy has taken action against 14 pharmacies, to revoke, suspend, or
summarily suspend licensure, or enter into a consent agreement for
surrender of licensure. None of the 14 instances involved violation of
the patient-specific prescription rule. The circumstances varied, and
include: Medicaid fraud (false claims to MassHealth), improper storage
or handling of drugs; failure to maintain proper sanitation;
repackaging and redispensing medications that had been returned; issues
involving sample medications; sale of drugs to an unlicensed entity;
and failing to keep medications properly labeled leading to dispensing
errors.
Staff formerly employed to support the Board of Pharmacy did not
maintain sufficient records to clearly delineate when actions were
shared with either the FDA or other relevant State Boards. Going
forward, the Department is conducting an extensive audit of all
operational policies and procedures in all nine (9) health professions
licensure boards supported by DPH staff. These efforts will facilitate
alignment of these entities, ensuring uniformity and enhanced quality
control of these critical functions.
Question 10. Please describe any standard operating procedures that
were put in place since September 25 to facilitate communication and
coordination with other boards of pharmacy. How is any disagreement
with another board of pharmacy resolved?
Answer 10. See response to Questions 3 and 5.
Question 11. How often do you contact other State boards of
pharmacy? Do you know which of your pharmacies ship out-of-state, and
do you ever get requests to inspect those facilities? How do you
respond to such requests?
Answer 11. On November 1, 2012, the Massachusetts Board of
Registration in Pharmacy adopted emergency regulations that include the
following provision:
``Every pharmacy licensed pursuant to M.G.L. c. 112, 39,
that performs central intravenous admixture services (CIVAS),
or engages in sterile compounding, shall report to the Board
every 6 months, or upon request by the Board, at a minimum, the
following information:
(a) total number of prescriptions dispensed, distribution
data identifying the States in which the prescriptions were
distributed, status of any non-resident licenses issued by
other States, hood certifications required by 247 CMR
6.01(5)(c) 5, status of CIVAS approval is) where applicable,
and any other information required by the Board.
(b) All such report shall be accurate and comply with the
Board's reporting requirements.
(c) All reports shall be accompanied by an affidavit
attesting compliance with all laws and regulations pertinent to
sterile compounding. This attestation shall be made under pains
and penalties of perjury, and include attestation to the
following: ``this registrant/licensee only prepares and
dispenses medication pursuant to a valid prescription as
defined in M.G.L.
c. 94C for a single patient, regardless of whether the
medication is prepared for a Massachusetts or out-of-state
patient.''--247 CMR 6.15(5).
Prior to enactment of these regulations, there was no formal
mechanism for designating which pharmacies shipped their products to
other States.
Question 12. I am concerned that if a State board wants to know the
history of a facility, not all the information is reported and it is
hard to know the full compliance history. I understand the National
Association of the Boards of Pharmacy keeps a database with this
information. Could you describe which of the numerous actions against
NECC in the past 14 years were reported to NABP, or how the actions
were made known to other State boards of pharmacy?
Answer 12. All of the dispositions taken against NECC were non-
disciplinary. As a result, none of the Board actions would have likely
been reported to the Healthcare Integrity Protection Data Bank (HIPDB)
and the National Practitioner Data Bank (NDBP). These actions included
the 1999 informal reprimand (against both NECC and Barry Cadden, the
co-owner and head pharmacist of NECC, as an individual), the September
30, 2004 advisory letters to NECC, the January 2006 consent agreement
(specifically agreed not to report), and the 2010 Ameridose complaints.
This highlights what I have said before: that poor judgment, missed
opportunities and a lack of appropriate action allowed NECC to continue
on this troubling path.
The Division of Health Professional Licensure (DHPL) reports
disciplinary actions against its licensees in several ways. First, the
Board reports disciplinary actions with respect to pharmacists and
pharmacy technicians to the HIPDB. The Board also reports disciplinary
actions with respect to pharmacies to the NPDB. In both instances,
Board staff prepares an internal report that Division staff use to
enter into the Federal databases within a day of action. The reported
disciplinary actions include not only the initial discipline imposed
(e.g., suspension of license), but also subsequent changes (e.g.,
reinstatement of licensure, with probationary status).
In addition to the foregoing, the Board maintains a spreadsheet,
listing the disciplinary licensing actions reported to HIPDB and NPDB.
As I mentioned before, under previous Board policy, non-disciplinary
actions were not reported publicly, something both the Board and the
Commission are actively reexamining. This spreadsheet is cumulative for
the period beginning in calendar year 2005 (fiscal year 2006) to the
present. During the first week of each month, Board staff updates this
spreadsheet with the NPDB and HIPDB reports made during the preceding
months. The spreadsheet is then emailed to individuals or entities on a
distribution list. The distribution list includes the National
Association of Boards of Pharmacy (NABP), specifically,
[email protected]. DPH cannot comment on NABP policy as to how
this information is then reviewed and shared more broadly.
Question 13. In general, what actions do you report to NABP
regarding pharmacies in Massachusetts? Could you describe the line
between what you must report, and what is not reported?
Answer 13. These tragic events have made one thing clear: timely
information and communication, acted on swiftly is critical in ensuring
public health and safety. As I have described in answering Question 12,
there are clear policies in place for Board staff to report these
incidents to NPDB and HIPDB.
ATTACHMENTS
______
Response of Marion Kainer to Question of Senator Whitehouse
Question. Dr. Kainer, your testimony notes that electronic health
records allowed ``tremendous'' savings in time and resources. How were
electronic health records used by health care providers and the
Tennessee Department of Health? Are there best practices you would
recommend for other State health departments regarding the use of
electronic health records during a public health crisis?
Answer. All of the hospital systems caring for patients in
Tennessee used an electronic health record to record most of their
health information when they were inpatients. At the beginning of our
investigation and response, as in past responses to other outbreaks, we
sent staff to the facilities to review key records on site and
requested faxed copies of other records. This approach provides access
to the needed records, but it is slow and involves many staff to
process all the requests. In general, these are the same hospital staff
who are needed at the healthcare facility as part of their response, so
their availability is limited.
In the context of an evolving outbreak, when the number of cases is
increasing rapidly and our understanding is evolving quickly, the
questions being asked are also rapidly changing. This leads to repeated
requests for additional records on both old and new patients. The
process of obtaining vital information can become very slow.
Early in this outbreak response, the Tennessee Department of Health
worked with all five hospital facilities caring for case patients to
obtain remote electronic access to inpatient medical records from
Health Department computers. This allowed our staff to quickly gather
additional information on existing patients and to initially review new
patient records, without having to visit the facilities or take the
time of medical staff to assist with access. This provided more
immediate and complete access to information than ever before.
As a result, we reduced the time to completing our analyses
substantially, leading to better information for patients and
clinicians in Tennessee, and the CDC. Rapid access to source data also
allowed us to quickly compose a detailed summary of our findings, which
was published in the New England Journal of Medicine * much more
quickly than if we had not had access to electronic records. This
allowed a broader audience to receive detailed information about the
outbreak they could use to guide patient evaluation and care.
---------------------------------------------------------------------------
* A summary of the findings mentioned may be found at www.nejm.org/
doi/full/10.1056/NEJMoa1212972.
---------------------------------------------------------------------------
Response of David G. Miller, R.Ph., to Questions of Senator Enzi,
Senator Casey, and Senator Franken
senator enzi
Question 1. How do you define traditional compounding? What, if
any, additional regulations should be placed on pharmacies that ship
large quantities of products interstate? Is there a larger Federal
role?
Answer 1. IACP does not have a definition of ``traditional''
compounding nor does one exist within our profession. We are very
concerned that this term has been referenced by numerous individuals,
organizations, and agencies and is both broad and subject to
significantly variable interpretation depending upon who is referencing
``traditional.''
We believe the focus should not be on the creation of a definition
of traditional vs. non-traditional but a more close examination of what
constitutes compounding--the preparation and issuance of a medication
upon receipt of a valid prescription from an authorized prescriber--and
what constitutes manufacturing--the preparation, promotion, selling and
distribution of a medication when no authorized prescriber is involved.
The manufacture of a medication cannot be judged, therefore, on the
basis of quantity. It is not the amount or even the process of
compounded medicine that is produced. Rather, it is an examination of
the transaction in and of itself. A very busy, very large pharmacy can
legitimately and appropriately compound and dispense medications intra-
or interstate based upon the receipt of valid prescriptions from
authorized prescriber and still remain a pharmacy. On the other hand, a
small pharmacy can be engaged in manufacturing if the preparation and
issuance of a compounded medication is done without a prescription or
medical order from an authorized prescriber.
We believe that an immediate area to be addressed is the
communication link between the State Boards of Pharmacy and the Food
and Drug Administration. State Boards are in the best position to
determine whether their license or permit holding pharmacies are
exceeding the scope of pharmacy practice and engaging in manufacturing-
like activities. In those instances, the State Board should have a
liaison or communication channel to the FDA for followup inspection and
action as the Federal agency has jurisdictional authority over
manufacturing including illegal manufacturing by pharmacies or other
entities.
Question 2. Are there basic standards that all sterile compounding
facilities should be held to, such as USP 797? How would that be
enforced?
Answer 2. IACP supports enactment of legislation or regulations
which mandates the compliance with USP <797> standards by any
practitioner or practice site involved in the preparation of sterile
compounds. That includes all pharmacists as well as physicians,
veterinarians or any other health care practitioner who compounds
sterile preparations. Additionally, all settings including hospitals,
home infusion companies, long-term care facilities, hospices, etc.,
should be held to the same accountability of adherence to these
industry-wide standards.
IACP also supports enactment of legislation or regulations which
mandates compliance with USP <795> standards by any practitioner or
practice site involved in the preparation of non-sterile compounds as
well.
Since States issue the licenses and permit for operation to a
pharmacy, they are the first enforcement agency that should be
responsible for conducting regular, unannounced inspections of all
sterile compounding facilities.
Should you have any further questions or wish clarification on our
responses, please do not hesitate to contact us. In the meantime,
please accept our best wishes for a wonderful holiday season.
senator casey
Question 1. How many prescriptions are filled annually by
compounding pharmacists, and of those, how many are filled in a non-
hospital/outpatient setting?
Answer 1. Unfortunately, no database exists which tracks all
prescriptions filled in the United States--compounded preparations
included. It has been estimated by the International Journal of
Pharmaceutical Compounding that 1-3 percent of all outpatient
prescriptions are compounded on an annual basis.
Question 2. When a compounding pharmacist ships drugs interstate in
response to a valid prescription, are the products shipped directly to
the patient or to the patient's provider? Does it depend on the type of
product?
Answer 2. It depends upon the prescription itself (the actual order
from the authorized prescriber), the type of medication ordered, the
directions given by the prescriber, and the express request of the
patient.
Some patient-specific medications can be delivered directly to the
patient or, if requested to do so by either the patient or the
prescriber, be delivered to the prescriber. In the latter case, that is
often done when the administration of the medication is done by the
prescriber him/herself. An example of that would be intrathecally
administered medicines. Because those drugs are infusions, the
integrity and stability of the medicine must be maintained. Minimizing
steps in transport (e.g., pharmacy to patient then patient to
physician) and controlling such things as temperature or security is
one means of assuring that integrity.
Question 3. How many of your members are accredited by the Pharmacy
Compounding Accreditation Board? Have these numbers been increasing?
Answer 3. As a professional society, IACP's membership is comprised
of individuals: pharmacists, pharmacy technicians, student pharmacists
and others involved in the specialty practice of compounding. The
Pharmacy Compounding Accreditation Board accredits pharmacies--the
physical business in which pharmacists practice. PCAB does not accredit
individual practitioners; therefore, no IACP member is accredited by
PCAB. As of December 1, 2012, PCAB currently accredits 168 pharmacies.
According to their staff, there are approximately 40 additional
pharmacies in various stages of the accreditation process. Since the
NECC crisis, PCAB has seen a 400 percent increase in applications by
pharmacies to begin the accreditation process.
Question 4. What is IACP doing to encourage its membership to
pursue accreditation and take other steps to ensure their compounded
products are safe?
Answer 4. IACP is a founding member of the Pharmacy Compounding
Accreditation Board (PCAB) and has many members serving on its standing
committees as well as providing a representative to its eight-person
board of directors. IACP provides PCAB with complimentary exhibits at
its national meetings and advertising space in its publications to
raise awareness of the Board. All new members of IACP also receive PCAB
information upon joining the Academy. Our most recent issue of our
electronic magazine--Custom Rx Connection--featured an extensive
article for the PCAB executive director. Additionally, our bi-weekly
electronic newsletter also announces all newly accredited and re-
accredited PCAB pharmacies as part of our efforts to promote
accreditation.
IACP conducts both live and web-based accredited continuing
education programs for its members and non-members on compounding
standards and safety. The Academy began a collaboration with the United
States Pharmacopeia (USP) earlier in 2012 which brings their seminars
on standards and safety to all pharmacists through our educational
portal.
Question 5. Dr. Hamburg discussed a possible risk-based framework
for the regulation of compounding, recognizing that certain compounded
products inherently pose a greater potential risk to patients should
they be handled improperly. Could you share your comments on FDA's
proposed framework?
Answer 5. Neither IACP nor its colleague professional associations
have been provided sufficient details to determine whether or not the
FDA's concept of a ``risk-based framework'' will lead to a meaningful
change in their enforcement of regulatory authority. We continue to
have a dialog with the agency to find solutions that will prevent a
future NECC-like catastrophe; however, as outlined by Commissioner
Hamburg, the proposed framework raises significant questions about
scope and intent.
Question 6. Do you feel that taking risk into account is
inappropriate? If so, what alternatives would you suggest?
Answer 6. IACP does not believe that the proposed framework from
the FDA fully defines the concept of ``risk'' as it is understood in
the professional practice community. Healthcare professionals are
trained to assess risk of therapy but the agency's definition is not
consistent with that commonly understood definition. Some medicines are
technically difficult to compound because of the nature of the drug
chemical or procedures necessary to obtain a finished preparation while
others are clinically risky and inappropriate because they are known to
have significant side effects and may cause harm to patients. Our
Academy believes that developing a consensus-based definition between
the pharmacy and medical practice communities in conjunction with State
and Federal regulatory authorities must be undertaken before any
framework can be addressed.
Question 7. How do you propose drawing a clear line between
traditional compounding for individual patients and large-scale
compounding that much more closely resembles manufacturing? Clearly,
there is confusion as to where this line is currently and where it
should be.
Answer 7. IACP's position is that there is a clear demarcation
between compounding and manufacturing. The issue is not whether a
pharmacy is compounding in ``large-scale'' amounts--a term that is
nearly indefinable--but whether they are compounding pursuant to a
valid prescription or medical order from an authorized prescriber.
Pharmacists dispense prescription drugs only when instructed to do so
through the form of a prescription or medical order. Manufacturing is
substantially different. A manufacturer is permitted to sell
medications to a facility, hospital, wholesaler, pharmacy or directly
to a prescriber without a prescription or medical order. Compounding
and dispensing is driven by prescriber decisionmaking. Manufacturing is
a purchase decision made without any prescriber input. All States
define what constitutes a ``valid prescription'' and also designate
which persons are considered ``authorized prescribers.'' IACP believes
that existing Federal statutory and regulatory language defines what
constitutes a manufacturer and that the Food and Drug Administration
has clear oversight authority in that arena.
senator franken
Question 1. In a report on meningitis in 2002, the Centers for
Disease Control and Prevention reported that ``some health-system
pharmacists might not realize that they are purchasing injectables
prepared through compounding.'' The CDC report continues by stating
that ``purchasers of pharmaceuticals should determine if supplies are
provided from a compounding pharmacy that is licensed in their State
and that follows appropriate measures to ensure that injectable
products are free of contamination.'' What responsibility do you
believe that purchasers of compounded products should have to make sure
that the products they're giving to their patients are safe?
Answer 1. IACP believes that all purchasers of compounded
preparations are as equally responsible for assuring the quality and
safety of the medications they obtain as they are for products
purchased from pharmaceutical manufacturers. That is a responsibility
which all pharmacists in the medication supply chain have been trained
to do and should do.
When it comes to compounded preparations, the responsibility is
even greater. Last year and in light of the ongoing drug shortage
situation, IACP developed a tool to assist physicians and pharmacists
in making informed decisions about professional partnerships with
compounding pharmacies. This tool includes a step-wise checklist that
includes such things as verification of licensure status, accreditation
status, standards and processes for regular testing and validation, as
well as recommendations to conduct an on-site interview and inspection.
Called the Compounding Pharmacy Assessment Questionnaire
(CPAQTM), IACP distributed that tool to State and national
medical, hospital, and pharmacy associations upon its release in
October 2011. A copy of the CPAQTM is included for your
review and is also available for download at the Academy's Web site
http://www.iacprx.org.
______
ATTACHMENTS
[International Academy of Compounding Pharmacists (IACPTM),
October 5, 2011]
IACP Provides Meaningful Solution With Compounding Pharmacy Assessment
Questionnaire
rising medication shortages affect patient health--new iacp tool helps
evaluate pharmacies for needed compounded medication services
Houston.--As hospital medication shortages continue to increase by
the day within the North American healthcare system, the International
Academy of Compounding Pharmacists (IACP) has developed a new
assessment questionnaire to assist hospitals, practitioners and non-
compounding pharmacies identify and evaluate compounding pharmacies as
they seek alternative sources for medications that currently are in
limited to complete shortage status.
IACP's Compounding Pharmacy Assessment Questionnaire
(CPAQTM) provides a comprehensive checklist of what to look
for in a compounding pharmacy practice and is based upon United States
Pharmacopeia (USP) standards which compounding pharmacists are
obligated to follow according to State board of pharmacy regulations or
standards of practice. Collaboration between licensed compounding
pharmacists and their colleagues in hospitals and institutions is a
long-standing solution to back-orders and shortages but the current
shortage situation is at a crisis point for many health-systems. The
expertise of a compounder with access to APIs (Active Pharmaceutical
Ingredients--the pure, raw drug ingredient) can mean the difference
between continued or initiation of much-needed medicines or an
unnecessary delay in patient care.
IACP's Compounding Pharmacy Assessment Questionnaire
(CPAQTM) includes evaluation points in the following areas:
Regulatory compliance
Licensing--permits
Internal controls and quality assurance
Testing & verification
Site visits
Linda F. McElhiney, PharmD, R.Ph., FIACP, FASHP, compounding
pharmacy operations coordinator, Indiana University Health, says,
``Drug shortages have been an ongoing problem for healthcare
facilities and the number of drug products that are unavailable
due to manufacturer backorders and discontinuation is on the
rise. These facilities are often trying to find substitutions
for the drug products or alternative treatments and there is
often a delay in the patients' treatment. Compounding
pharmacies may be able to prepare these medications using bulk
active pharmaceutical ingredients; however, it may be difficult
for the healthcare pharmacy administrators to know if the
compounding pharmacy can provide quality compounded medications
to meet their facilities' needs because they are unfamiliar
with the USP standards for compounding sterile and non-sterile
preparations. The International Academy of Compounding
Pharmacists (IACP) has developed a checklist of standards and
criteria to assist the administrators in finding a suitable
compounding pharmacy to meet these needs.''
Scott Karolchyk, R.Ph., FIACP, IACP president-elect, says,
``IACP leadership recently participated in FDA's conference
on prescription drug shortages. While there were many good
intentions expressed during the conference, there were no real
solutions for now. Each day, pharmacists and physicians are
grappling with making sure our patients get the medicines they
need. What was clearly overlooked was how compounding
pharmacists are providing solutions today as they work with
U.S. hospitals, surgery centers, and practitioners to make
those medicines available.''
John Herr, R.Ph., IACP president, asked, ``What better solution to
this problem than pharmacists working intraprofessionally to take care
of patients?''
``The CPAQ tool is compounding pharmacy's way of stimulating
that relationship. Given that compounders have an outstanding
track record for preparing quality medications on a per-
prescription basis, we know that working together will lessen
the need to use the so-called `gray market' of suppliers,
distributors and others which are taking advantage of people in
need.''
about iacp
The International Academy of Compounding Pharmacists (IACP) is a
professional association founded in 1991 to protect, promote and
advance personalized medication solutions. The association represents
more than 2,100 pharmacists and pharmacist technicians licensed and
regulated by their individual State boards of pharmacy and located
throughout North America, South America, Europe, Australia and Asia. In
addition, IACP represents more than 154,800 patients, physicians, nurse
practitioners and veterinarians through its ally grassroots
organization, Patients & Professionals for Customized Care (P2C2). IACP
is committed to ensuring the rights of physicians to prescribe, of
pharmacists to prepare, and of patients to take personalized medication
solutions that meet their unique, individual health needs.
IACP offers a free Compounding Pharmacy Locator Service which can
be accessed toll free at (800) 927-4227 or via IACP's Web site at
www.iacprx.org.
Response by Kasey K. Thompson to Questions of Senator Enzi,
Senator Casey and Senator Franken
senator enzi
Question 1. USP updated their standards for sterile compounding 5-
10 years ago. Since then, have you seen an increase in outsourcing of
sterile compounding?
Answer 1. USP 797 became official in 2004 and underwent a major
revision in 2008 that included additional requirements.
Below are results from ASHP's May 2011 survey demonstrating
increased outsourcing:
In 2011, 70.9 percent of hospitals reported partially or
completely outsourcing some drug preparation activities. A greater
percentage of larger hospitals outsource some preparation activities
compared with smaller hospitals. For example, 96.9 percent of hospitals
with 600 or more staffed beds out-sourced some part of preparation
activities, compared with 49 percent of hospitals with fewer than 50
staffed beds. The outsourcing of some preparation activities has
increased over time, from 21 percent of hospitals in 2002 to 31 percent
in 2005 and 42 percent in 2008.
Of hospitals that out-sourced some part of preparation
activities, 73 percent out-sourced patient-controlled analgesia (PCA)
and epidural analgesia preparations, 65 percent out-sourced oxytocin
preparations, and 38 percent out-sourced some i.v. admixtures and
minibags (Table 10). About 25 percent of hospitals out-sourced syringe-
based anesthesia medications, total parenteral nutrition (TPN)
preparations, and flushes. Hospitals less frequently out-sourced
cardioplegia preparations, unit dose drug repackaging, and unit dose
repackaging for bar coding. The percentages of hospitals outsourcing
PCA and epidural analgesia preparations, i.v. admixtures or minibags,
and flushes have increased during the past 9 years, while the
outsourcing of TPN preparations has declined.
Table 10.--Preparation Activities That Are Either Partially or Completely Outsourced, Excluding Services Through a Contract Pharmacy Services Provider
--------------------------------------------------------------------------------------------------------------------------------------------------------
Patient-
controlled I.V.
analgesia Admixtures Syringe- Total Unit dose Unit dose
Characteristic n and Oxytocin and small- based parenteral Flushes Cardioplegia repackaging repackaging
epidural volume anesthesia nutrient solutions (drug only) for bar
analgesia I.V. medications solutions coding
preparations solutions
--------------------------------------------------------------------------------------------------------------------------------------------------------
No. Staffed Beds:...............
<50........................... 51 70.6 52.9 27.5 11.8 21.6 25.5 3.9 11.8 3.9
50-99......................... 56 73.2 60.7 42.9 16.1 16.1 21.4 3.6 16.1 10.7
100-199....................... 63 68.3 66.7 42.9 23.8 17.5 22.2 15.9 12.7 6.3
200-299....................... 69 76.8 76.8 39.1 30.4 29.0 21.7 23.2 15.9 11.6
300-399....................... 54 77.8 63.0 40.7 38.9 31.5 16.7 37.0 22.2 24.1
400-599....................... 86 79.1 81.4 44.2 38.4 32.6 18.6 41.9 20.9 19.8
600........................... 62 88.7 72.6 40.3 41.9 45.2 25.8 64.5 40.3 22.6
All hospitals--2011............. 441 73.3 65.2\1\ 38.3 24.1\2\ 23.6 22.2 18.3\3\ 16.0 10.4\4\
All hospitals--2008\3\.......... 270 64.0 \5\ 37.3 32.8 13.9 13.4 14.6
All hospitals--2005\6\.......... 186 40.2 31.4 39.8 12.8 11.6 9.6
All hospitals--2002\9\.......... 137 16.7 15.7 52.4 9.1 12.1 8.9
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Uncorrected x\2\ = 16.4578, df = 6, designed-based F(4.17, 1810.24) = 3.0517, p = 0.0147.
\2\ Uncorrected x\2\ = 24.0577, df = 6, designed-based F(4.19, 1817.03) = 4.2945, p = 0.0015.
\3\ Uncorrected x\2\ = 71.3848, df = 6, designed-based F(4.21, 1825.56) = 12.4305, p = 0.0001.
\4\ Uncorrected x\2\ = 20.8045, df = 6, designed-based F(4.20, 1824.14) = 3.5927, p = 0.0055.
\5\ Not surveyed.
In April 2012, Pharmacy Purchasing and Products published its own
survey.
In general these results demonstrate a gradual increase (from 56
percent to 65 percent) in outsourcing since the establishment of USP
797 standards for compounding sterile products in 2008. While 76
percent of respondents reported outsourcing in response to a drug
shortage, safety and the ability to provide a ready to administer
dosing form were equally significant reasons as demonstrated by out-
sourced patient controlled analgesia (67 percent), epidural injections
(48 percent), controlled substances (35 percent) and pre-filled OR
medications (34 percent). (See graphs below.)
senator casey
Question 1. Do you believe that hospitals and health systems that
outsource their compounding to external compounding pharmacies are
sufficiently able to determine whether those pharmacies are producing
safe products?
Answer 1. Pharmacists have the expertise to help evaluate if
compounding is being conducted in accordance with Federal and State
definitions and standards established by the U.S. Pharmacopeia in
Chapter 797. However, the ability of hospitals to conduct routine
inspections of compounding entities is limited by resources, which is
why it is important to have a Federal and State oversight system that
ensures that these entities are capable of producing safe products in
accordance with Federal and State laws. The American Society of Health-
System Pharmacists also has guidelines and assessment tools available
to help hospitals evaluate outside entities that provide compounded
formulations. ASHP Guidelines on Outsourcing Sterile Compounding
Services http://www.ashp.org/DocLibrary/Bestpractices/Mgmt
GdlOutsourcingSterileComp.aspx; ASHP Foundation: Outsourcing Sterile
Products Preparation Contractor Assessment Tool http://
www.ashpfoundation.org/Main
MenuCategories/PracticeTools/SterileProductsTool/
SterileProductsAssessmentTool.
aspx.
Most pharmacists are not trained to evaluate manufacturing-level
facilities where Current Good Manufacturing Practices (cGMPs) are
applicable. Examples are bulk compounding of sterile preparations from
(1) nonsterile ingredients or (2) from sterile ingredients using
aseptic processing * and storing these medications for periods beyond
those associated with compounding.
---------------------------------------------------------------------------
*Aseptic processing uses sterile components to make a sterile final
product. Sterility must be maintained through multiple manipulations
which introduces more variables than formulation of products that are
terminally sterilized.
Question 2. Do you think that the compounded products typically
used in a hospital or in-patient setting are different from other
products typically used in outpatient settings, and if so, do you think
that they should be subject to additional or different regulation?
Answer 2. The environment in which these medications are used is
less important than the environment in which they must be prepared. The
difference is whether the compounded product is a sterile preparation,
such as an injectable, or ophthalmic medication. The preparation area
is highly controlled to prevent contamination using methods that
include in-process and final product quality assurance procedures. The
applicable standards, USP 797, are adequate for compounding sterile
preparations in hospitals.
Question 3. Under the current patchwork system of State and Federal
regulation, do you think products compounded in a hospital pharmacy are
safer or less safe than products compounded at freestanding compounding
pharmacies?
Answer 3. Compounded sterile products from pharmacies that are made
pursuant to or in anticipation of a medication order or prescription
and according to USP 797 standards are equally safe, whether the
pharmacy is in a hospital or community setting.
However, a sterile compounding business entity that does not fill
prescriptions for individual patients is not a pharmacy. Regulatory
oversight of these entities should be dependent on the scope and scale
of their operations, which may range from patient-specific small
batches to large-scale production of commonly used drugs or dose forms
based on historical demand. The beyond use date (BUD) or shelf life
these entities assign to final products as well as the risk level (low,
medium, high) of the compounding activity are also factors.
These entities are neither a pharmacy nor a manufacturer, but fall
somewhere in between into a regulatory gray area. An intermediate
category of drug establishment with criteria for inclusion and
clarification of regulatory oversight should be developed.
senator franken
Question 1. In a report on meningitis in 2002, the Centers for
Disease Control and Prevention reported that ``some health-system
pharmacists might not realize that they are purchasing injectables
prepared through compounding.'' In your experience, is this sometimes
the case? If so, what responsibility do you believe that purchasers--
including health systems--have to ensure that they are providing their
patients with safe medicines?
Answer 1. Lack of clarity regarding the nature of drug
establishments that register with the FDA may in fact mislead
pharmacists to believing they are purchasing products from a legitimate
manufacturer, rather than a compounding pharmacy. Compounding
businesses advertise that they are ``registered with FDA,'' and are
listed on FDA's Web site, however, their registration categories are
not disclosed. Thus, pharmacists may not be aware they are contracting
with a retail pharmacy, a regional admixture pharmacy, or a
manufacturing pharmacy, rather than an entity with FDA oversight.
Pharmacists are accountable for the safety and quality of the
products they dispense, including those obtained from contracted
services. It should be recognized, however, that pharmacists have
little control over how these businesses are operated. Regardless of
State or Federal oversight, a licensed business subject to statutory
and regulatory requirements and offering products or services for sale
should not be allowed to shift liability for its products to the end
users.
Question 2. In your written testimony, you state, ``Previous court
rulings have made FDA's authority to inspect these facilities unclear
and subject to legal action.'' Would you expand on this statement?
In order to determine whether a pharmacy is acting like a
manufacturer, should FDA have the authority to inspect the records and
processes of pharmacies that they believe may be acting improperly?
Answer 2. It is our understanding that FDA has limited authority to
inspect large scale compounding entities since most are essentially
operating as pharmacies. We believe that FDA's authority needs to be
clarified or new authorities given to FDA to regulate compounding
businesses that produce large amounts of compounded products, and sell
those products to entities other than the end user. We believe that FDA
and State boards of pharmacy will need to work together more closely to
determine when a compounding pharmacy should be placed into a new or
clarified category of FDA oversight.
[Whereupon, at 12:51 p.m., the hearing was adjourned.]