[Federal Register Volume 66, Number 163 (Wednesday, August 22, 2001)]
[Notices]
[Pages 44146-44149]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-21145]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Notice of Meeting
AGENCY: Office of the Secretary, HHS.
ACTION: Notice of meeting.
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At the request of the Secretary, a meeting will be held to
determine if and how the Public Health Service Bovine Spongiform
Encephalopathy/Transmissible Spongiform Encephalopathy (BSE/TSE) Action
Plan can be expanded to capitalize on the human and physical resources
of the pharmaceutical and biotechnology industries. A copy of this plan
is appended to this Notice. The meeting will be held in the Office of
the Secretary, Hubert H. Humphrey Building, 200 Independence Ave. SW.,
Washington, DC 20201 on Monday, September 24, 2001, from 9 a.m. to 3
p.m. Because of space limitations, attendance at the meeting will be
limited to approximately 100 persons, and will therefore be limited to
those who have preregistered.
Up to 30 of the approximately 100 spaces available will be reserved
for those who submit a written proposal of no more than two single-
spaced pages in length, and preferably no more than one page, that
describes in general terms (1) needs in areas of basic research on any
aspect of BSE or any TSE that are currently unmet and (2) human and
physical resources under their control that could be recruited to
support this research. This solicitation of ``industries'' is directed
at industries of all sizes, and to non-profit as well as for-profit
entities.
Preference for the 30 reserved spaces will be given to those whose
proposals are received by the undersigned no later than close of
business Friday, August 31, 2001. A paper copy and an electronic copy
in either Microsoft Word (R) or WordPerfect (R) format are requested,
but fax and e-mail submissions will be accepted. Proposals must include
a return mailing address, individual to contact, and telephone number
of that individual. If available, a fax number and an e-mail address
should also be provided.
A period of up to one hour will be reserved for public comment.
Persons who wish to comment on their own proposal or any other matter
will be asked to do so for no more than 5 minutes.
The sole purpose of this meeting is to gather information. No
decisions will be made at this meeting. A transcript and a summary of
the meeting will be available from the undersigned on or before October
8, 2001.
Those considering submission of a proposal or speaking at the
meeting are advised that all information received in response to this
Notice will be considered to be in the public domain.
For Registration or Further Information Contact
Stephen D. Nightingale, M.D., Office of Public Health and Science,
Department of Health and Human Services, 200 Independence Ave., SW.,
Washington, DC 20201, phone (202) 690-5558, fax (202) 260-9372, e-mail
[email protected].
Dated: August 17, 2001.
Stephen D. Nightingale,
Executive Secretary, Advisory Committee on Blood Safety and
Availability.
Bovine Spongiform Encephalopathy/Transmissible Spongiform
Encephalopathy (BSE/TSE) Action Plan
Background
Bovine spongiform encephalopathy (BSE), or ``mad cow disease,'' was
first recognized in the United Kingdom in 1986. Major efforts were
undertaken to control the BSE epidemic that followed. These included
the precautionary slaughter of about 4.5 million asymptomatic cattle,
and increasingly broader prohibitions against recycling animal tissues
and byproducts into the food chain through livestock feed supplements.
There is compelling epidemiological evidence that these actions
reversed the course of the BSE epidemic within the United Kingdom.
Unfortunately, these measures were insufficient, or not instituted
in time, to prevent the occurrence of BSE in other European countries.
These initially included France, Ireland, Portugal, and
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Switzerland, and have more recently included Belgium, Denmark, Germany,
Italy, Netherlands, and Spain. However, BSE has not yet been found in
the United States.
BSE is one of several transmissible spongiform encephalopathies
(TSEs). Other animal TSEs include scrapie in sheep and goats, and
chronic wasting disease (CWD) of deer and elk. Scrapie and CWD are
found in the United States. Human TSEs include kuru, a disease of the
South Pacific Fore people; Creutzfeldt-Jakob disease (CJD), which
occurs throughout the world, including the United States (where it
occurs at a stable rate of about 1 per million population per year);
and new variant CJD (vCJD), which was first reported in the United
Kingdom in 1996. There is no evidence to date of vCJD in the United
States. There is no known treatment for any TSE, and they are all
invariably fatal.
The TSEs are named for the characteristic spongelike appearance
associated with deposits of proteins, called prions, that are found in
patients' brains. In some but not all TSEs, there are characteristic
deposits of prions, sometimes detectable preclinically, in other
tissues as well. Prions are proteins that have been highly conserved in
mammalian evolution, but whose function is not well understood. They do
not cause disease in their native state, but only when they become
abnormally folded.
What causes the abnormal folding to occur, why affected individuals
cannot dispose of or develop immunity to these proteins, and what
factors other than the prions themselves affect the transmission or the
pathogenesis of the TSEs are poorly understood. In particular, the lack
of a sensitive and specific noninvasive test for either animal or human
TSEs, or methods for identifying those at increased risk of a TSE, are
major obstacles to progress. However, recent investigations in this
field appear to hold substantial promise.
Issue
The report of vCJD (a disease of humans) in the United Kingdom only
ten years after the recognition of BSE (a disease of animals) was by
itself an event of great concern. This concern has been reinforced by
the findings that the transmissible agent of BSE and the transmissible
agent of vCJD are indistinguishable by current bioassays from each
other; that BSE has spread from the United Kingdom to other countries,
and that vCJD has begun to appear in some countries to which BSE has
spread. These events call for a vigorous DHHS effort--coordinated with
those of other government agencies, the private sector, and the
international community--to contain this epidemic and assist those
affected by it.
Response
The BSE/TSE Action Plan of the Department of Health and Human
Services (DHHS) has four major components: Surveillance, Protection,
Research, and Oversight. Surveillance for human disease is primarily
the responsibility of the Centers for Disease Control and Prevention
(CDC). Protection is primarily the responsibility of the Food and Drug
Administration (FDA). Surveillance of animals, feeds, and foods is also
a responsibility of FDA, which it shares with the United States
Department of Agriculture (USDA). Research is primarily the
responsibility of the National Institutes of Health (NIH). Oversight is
primarily the responsibility of the Office of the Secretary (OS). Core
actions in each area are as follows:
1. Surveillance--CDC
A foundation of CDC disease surveillance and outbreak investigation
activities is its relationship with--and support of--state and local
health agencies and officials, who are often the first to encounter
newly emerging human diseases or changes in the epidemiology of
recognized human diseases. These relationships complement those that
CDC maintains with health care providers and institutions such as
healthcare facilities. These relationships are designed to maximize the
likelihood that a sentinel event will be detected as soon as it occurs,
whether in an expected or an unexpected location.
CDC collects, reviews, and when indicated actively investigates
reports by health care personnel or institutions of possible CJD or
vCJD cases. CDC also monitors overall mortality data and carefully
scrutinizes mortality data in certain populations (for example, persons
with hemophilia). In addition, after the report of vCJD in the United
Kingdom in 1996, CDC augmented its domestic CJD surveillance. Because
of the striking age differences between vCJD and CJD patients, CDC, in
partnership with state and local health departments, initiated post-
mortem followup investigations of patients diagnosed with CJD who were
less than 55 years of age at death. In 1996-1997, CDC established, in
collaboration with the American Association of Neuropathologists, the
National Prion Disease Pathology Surveillance Center at Case Western
Reserve University, which performs special post-mortem tests for vCJD.
Under this Action Plan, CDC will provide additional financial and
technical support for state and local health department surveillance
for CJD and vCJD cases. The Action Plan anticipates the need for more
case investigations and risk assessments, particularly if the
epidemiology of vCJD changes. The action plan will increase the range,
accuracy and timeliness of current efforts.
The proposals are as follows:
A. By the end of 2001, CDC will support cooperative agreements with
state and local health departments to:
i. Enhance pre-mortem surveillance to increase the number of post-
mortem studies on individuals, who by virtue of their symptoms (e.g.,
ataxia or dementia) and situations (e.g., long exposure to food
products from the United Kingdom) might be at increased risk for TSEs,
and
ii. Expedite national surveillance of CJD through accelerated
review of CJD mortality data and clinical investigation of all such
cases under 55 years of age to identify possible cases of vCJD.
B. CDC will enhance its current collaborative agreement with the
National Prion Disease Pathology Surveillance Center at Case Western
Reserve University by the end of FY 2001.
C. CDC will enhance and expand infection control recommendations to
protect patients and health care workers from the potential
transmission of TSE in healthcare facilities by the end of FY 2002.
D. CDC will maintain and, as appropriate, expand its contact with
national and local health officials in countries that have found, or
may find, new or increasing numbers of animal or human TSEs within
their borders (FDA and NIH, in the course of actions described below,
will do the same with their regulatory and scientific counterparts).
The following additional activities and expansion of A above will
require additional or reallocated resources.
A. CDC will enhance and expand its technical assistance to the
increasing number of state and local health personnel whom these
cooperative agreements will make available to identify and investigate
possible cases of TSEs.
B. CDC will develop laboratory capacity at its main campus to
provide analytic support for health investigations, and to conduct
research on methods to improve these investigations by the end of FY
2003. This activity will depend on the
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completion of new laboratory space, anticipated to become available in
FY 2004.
2. Protection--FDA
The foundations of FDA consumer protection and health promotion
activities are rigorous application of scientific knowledge to
regulatory policies and actions, appropriate caution when scientific
knowledge is insufficient to determine the optimal policy or action, a
strong regulatory infrastructure to assure compliance with established
regulations, and aggressive pursuit of the scientific knowledge
necessary to anticipate as well as resolve regulatory issues.
Maintenance of an environment in which these practices can flourish
requires timely and open dialogue about the agency's actions, and the
reasons for its actions, with both stakeholders on specific issues and
with the public at large.
Consistent with this overall strategy, FDA has undertaken five
major initiatives to enhance, sustain, and communicate safeguards.
These are:
A. FDA, in partnership with USDA, seeks to prevent exposure of the
public to TSE agent(s) through food products. FDA will continue and as
necessary expand its import and animal feed surveillance/inspection
programs and enforcement actions to control the use of mammalian
protein in ruminant feed, to keep potentially infected products out of
the United States, and to address further the issue of CWD in domestic
deer and elk.
B. FDA will continue and as necessary expand its policies designed
to prevent potential exposure to TSE agent(s) through blood transfusion
and tissue transplantation. Reevaluations occur both on a routine, at
least semi-annual basis in conjunction with meetings of the FDA TSE
Advisory Committee, and whenever new information becomes available.
C. FDA will continue and as necessary expand its policies to
prevent potential exposure of the public to TSE agent(s) through drugs,
devices, vaccines, other biologics, cosmetics, food, food additives, or
dietary supplements that use in their manufacture at-risk bovine
materials. These efforts are routinely incorporated into the pre-
approval review of new entities that are required to undergo such
review, and by targeted post-marketing review of specific entities that
may either contain at-risk bovine materials, or entities that may be
exposed to at-risk bovine materials during their manufacture. Ongoing
enhancements to guidances and regulations regarding acceptability of
source materials for these products are an integral component of this
effort.
D. FDA will continue and as necessary expand its coordinated
education and outreach program to inform consumers, patients,
practitioners, and industry of the risks of TSEs and of their potential
transmission through the products that FDA regulates.
E. FDA will continue and as necessary expand its regulatory
research agenda regarding TSEs. As noted above, the lack of a
sensitive, specific, and non-invasive test to detect either humans or
animals with an increased risk of developing or incubating a TSE is a
major obstacle to progress against TSEs, and to FDA's efforts to meet
its consumer protection and health promotion mandates. While FDA is
encouraged by recent progress in this field, FDA nevertheless feels
obligated to continue both intramural and extramural research to
support the development and evaluation of tests for premortem detection
of TSE agents(s) that will have sufficient sensitivity and specificity
for diagnostic, screening, and quality control purposes. FDA will also
pursue studies to evaluate the safety and effectiveness of
sterilization/decontamination/inactivation procedures for BSE/TSE
agent(s) so that these procedures can become part of Good Manufacturing
Practices.
3. Research--NIH
A foundation of NIH research portfolio management is to maintain a
balance between its support of research focused on health matters of
immediate concern, and research that aspires to address concerns that
may arise in the future. The NIH supports both intramural and
extramural research, some of which is guided by agency directives, and
some by proposals of individual investigators. In addition to fostering
individual proposals, the NIH fosters the training and professional
development of the young investigators necessary to sustain the
country's research efforts in the future.
The first scientific work on human TSE to be undertaken anywhere in
the world was initiated on the NIH campus in the early 1960's.
Currently NIH funding for TSE research, which is provided for
investigators throughout the United States, is focused on four areas:
i. Understanding the prions that cause TSEs;
ii. Defining how TSEs are transmitted among animal species and,
most importantly, across apparent species barriers;
iii. Developing diagnostic tests for animals and humans using
tissues and blood;
iv. Designing drug therapy.
Pursuant to these goals, major TSE research programs are currently
being supported by the following institutes:
i. The National Institute of Neurological Disorders and Stroke
(NINDS) supports basic and applied research on TSEs in both its
intramural and extramural programs. Prior accomplishments of the
intramural program have been recognized by the award of the Nobel Prize
to Dr. Carleton Gadjusek for demonstrating that both kuru and CJD were
transmissible, and prior accomplishments of the extramural program have
been recognized by the award of the Nobel Prize to Dr. Stanley Prusiner
for his work on prions. NINDS funding for TSE research was $8.87
million in FY 1999 and $12.75 million in FY 2000.
ii. The National Institute of Allergy and Infectious Diseases
(NIAID) also supports both intramural and extramural research on TSEs,
with a particular focus on chronic wasting disease (CWD) of deer and
elk. The intramural NIAID program, which is conducted at the NIAID
Rocky Mountain Laboratories in Hamilton, Montana, has developed
genetically engineered mouse models of scrapie and CWD and used these
to study the effects of particular genes and of species barriers on the
natural history of these diseases. The laboratory has also initiated a
drug discovery program. Renovation of the Rocky Mountain facilities
devoted to TSE research is currently under way, at a cost of $1.62
million dollars. In FY 2002, NIAID expects that roughly $1 million will
be allocated to the Rocky Mountain Laboratories for support of TSE-
related research.
iii. The National Heart, Lung, and Blood Institute (NHLBI) is the
lead institute within NIH for the development of tests for TSEs that
would be suitable for screening the blood supply. The research
currently funded is targeted at developing and validating test
strategies for various human and animal TSEs in samples of known
infectivity. This program includes two contracts jointly sponsored by
NHLBI and NINDS that run from fall 2000 to fall 2005 and three NHLBI-
initiated research grants that run from fall 2000 to fall 2003. NHLBI
funding for TSE research was $0.9 million in FY 1999 and $2.2 million
in FY 2000.
Efforts in all of the above areas are being expanded. However,
there is a critical shortage of investigators and specialized
laboratory facilities that can
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handle the hazardous material used in studies of TSEs. A goal of the
NIH is to address these needs by mounting a coordinated effort among
the Institutes at NIH as well as with other Federal agencies to achieve
these objectives:
A. Establish a repository for research reagents by the next fiscal
year;
B. Double the laboratory facilities available over the next two
years;
C. Triple the number of investigators involved in TSE research over
the next five years;
D. Double or if possible triple current spending for TSE research
by the end of FY 2002. To do this, the NIH will convene a special
meeting to identify the major needs and opportunities for research in
this field. The product of this workshop will form the basis of a
Request for Applications. The scientific quality of the applications
received will determine the total funding committed to this initiative.
The Acting Director, NIH, has agreed to provide funding as needed for
this purpose from the Director's Discretionary Fund.
E. Consider, in consultation with OS, the establishment of a
``prize'' of about $1 million for the first person(s) or
organization(s) to provide proof of principle for the development of a
minimally invasive test that would be sufficiently sensitive and
specific for screening random populations for presymptomatic infection
with CJD or vCJD, and a ``prize'' of about $5 million to the first
person(s) or institution(s) to obtain FDA approval and to place into
commercial distribution a minimally invasive screening test that would
be sufficiently sensitive and specific for screening random populations
for presymptomatic infection with CJD or vCJD.
4. Oversight--OS
The foundations of OS oversight activities are the statutory
obligations of the Secretary, and the lessons that have been learned
from experience with the HIV and hepatitis C epidemics.
In 1995, at the request of the Department, the Institute of
Medicine (IOM) issued a report titled ``HIV and the Blood Supply: An
Analysis of Crisis Decisionmaking.'' The IOM recommended that the
Secretary establish a Public Health Service (PHS) Blood Safety
Committee (BSC). The Secretary designated the Assistant Secretary for
Health to be the chair of this committee and to be the Blood Safety
Director for the Department. Other BSC members are the directors of
CDC, FDA, and NIH; the Assistant Secretary for Planning and Evaluation;
and the Associate General Counsel for Public Health. This committee
exists so that threats to the safety or availability of the blood
supply can be brought immediately to the highest levels of the
Department. The BSC has met on the issue of deferring blood donors at
risk of transmitting BSE by virtue of prior residence in the United
Kingdom. The BSC also met on issues relating to the development of CJD
at an unusually young age in a hunter who had been a long time plasma
donor, and on issues related to the discovery of a poorly characterized
TSE that recently appeared in two flocks of East Freisian sheep which
had been imported to Vermont from Belgium. The group stands ready to be
convened for similar matters in the future.
The Department has also established an Interdepartmental Steering
Committee for BSE/TSE Affairs. This committee is chaired by the
Commissioner of FDA and includes representatives of CDC, FDA, NIH,
USDA, the United States Trade Representative, the Office of Management
and Budget, the Customs Service, the Department of State, the
Department of Defense, the State Association of Feed Control Officials,
the National Association of State Departments of Agriculture, and the
White House Office of Science and Technology Policy. This committee
assures ongoing coordination between agencies; integrated contingency
planning in case BSE or of vCJD is found in the United States;
identification of and response to potential vulnerabilities in the
United States to BSE and vCJD; and coordination of risk communication
plans by the various agencies. A summary of each meeting of this group
will be forwarded through the Assistant Secretary of Health to the
Secretary within thirty days of each meeting, and on a more expedited
basis as necessary.
The Department must assure timely, accurate, thorough, and clear
communication to the public about the nature and extent of the threats
posed by BSE/TSE and about the actions that each agency of government
is taking to protect the public from these threats. In addition, each
agency must anticipate the worst case scenarios of a case of BSE or of
vCJD being recognized in the United States, and each agency must have a
plan not only for dealing with this contingency but also for
communicating the event itself, and the agency response to the event,
to the public. Furthermore, the communications of the various agencies
must be consistent with each other. For this reason, the BSE/TSE
Steering Committee will establish a communications workgroup to develop
an interdepartmental communications strategy and plan for dealing with
a potential occurrence of BSE and/or vCJD and serve as a public
affairs/communications resource in dealing with BSE/TSE issues.
Also, the FDA TSE Advisory Committee meets publicly on at least a
semi-annual basis. One standing agenda item of this committee is review
of current regulations and guidance to prevent exposure of the United
States population to the agent(s) of BSE/TSE through blood, tissues,
and other regulated products. A summary of this meeting, with
particular attention to this agenda item and to public comment about
it, will be forwarded through the Assistant Secretary for Health to the
Secretary within thirty days of each meeting, and on a more expedited
basis as necessary.
Issues that warrant OS oversight at this time include the
following:
A. Assurance of adequate program support to enhance TSE
surveillance by CDC as planned.
B. Assurance of adequate program support for FDA regulatory and
research activities related to TSEs.
C. Assurance of adequate program support for the TSE research
initiatives proposed by NIH.
D. Assurance and coordination of integrated risk communication
messages to the public and to industry regarding the true nature of
threats posed by BSE/TSEs, particularly in the event of a confirmed
case within the United States.
E. Assurance of a seamless collaboration with USDA and other
federal and state agencies on BSE/TSE issues.
[FR Doc. 01-21145 Filed 8-21-01; 8:45 am]
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