[Federal Register Volume 73, Number 189 (Monday, September 29, 2008)]
[Proposed Rules]
[Pages 56529-56533]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-22829]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 314
[Docket No. FDA-2008-N-0341]
Applications for Food and Drug Administration Approval to Market
a New Drug; Postmarketing Reports; Reporting Information About
Authorized Generic Drugs; Companion Document to Direct Final Rule
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is publishing this
companion proposed rule to the direct final rule, published elsewhere
in this issue of the Federal Register, which is intended to amend our
regulations to require that the holder of a new drug application (NDA)
submit certain information in an annual report regarding authorized
generic drugs. We are taking this action as part of our implementation
of the Food and Drug Administration Amendments Act of 2007 (FDAAA).
FDAAA requires that FDA publish a list of all authorized generic drugs
included in an annual report since 1999, and that the agency update the
list quarterly.
DATES: Submit written or electronic comments on the proposed rule by
December 15, 2008. If FDA receives any significant adverse comments,
the agency will publish a document withdrawing the direct final rule
within 30 days after the comment period ends. FDA will then proceed to
respond to comments under this proposed rule using the usual notice and
comment procedures. Submit comments on information collection issues
under the Paperwork Reduction Act of 1995 by October 29, 2008 (see the
``Paperwork Reduction Act of 1995'' section of this document).
[[Page 56530]]
ADDRESSES: You may submit comments, identified by Docket No. FDA-2008-
N-0341, by any of the following methods, except that comments on
information collection issues under the Paperwork Reduction Act of 1995
must be submitted to the Office of Regulatory Affairs, Office of
Management and Budget (OMB) (see the ``Paperwork Reduction Act of
1995'' section of this document).
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal, as described previously, in the ADDRESSES portion
of this document under Electronic Submissions.
Instructions: All submissions received must include the agency name
and docket number for this rulemaking. All comments received may be
posted without change to http://www.regulations.gov, including any
personal information provided. For additional information on submitting
comments, see the ``Request for Comments'' heading of the SUPPLEMENTARY
INFORMATION section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number(s), found in brackets in the heading of this document,
into the ``Search'' box and follow the prompts and/or go to the
Division of Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
FOR FURTHER INFORMATION CONTACT: Michelle D.D. Bernstein, Center for
Drug Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave. Bldg. 51, rm. 6223, Silver Spring, MD 20993-0002, 301-
796-3601.
SUPPLEMENTARY INFORMATION:
I. Background
As described more fully in the direct final rule, FDAAA requires
that FDA take the following actions: (1) Publish on its Internet site a
complete list of all authorized generic drugs included in an annual
report submitted to the agency after January 1, 1999; (2) update the
list quarterly; and (3) notify relevant Federal agencies that the list
has been published and will be updated quarterly. For purposes of
publishing the list, section 505(t)(3) of the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 355(t)) defines the term ``authorized
generic drug'' as a ``listed drug (as that term is used in [section
505(j) of the act]) that has been approved [under section 505(c) of the
act] and is marketed, sold, or distributed directly or indirectly to
retail class of trade under a different labeling, packaging (other than
repackaging as the listed drug in blister packs, unit doses, or similar
packaging for use in institutions), product code, labeler code, trade
name, or trade mark than the listed drug.''
We are proposing to amend Sec. 314.3 (21 CFR 314.3) of our
regulations by adding a definition of ``authorized generic drug.'' To
allow FDA to accurately report a complete list of all authorized
generic drugs included in annual reports and to update the list in a
timely fashion, we are proposing to amend Sec. 314.81 (21 CFR 314.81)
by adding paragraph (b)(2)(ii)(b), which would require that annual
reports specifically and clearly include the information we are
required to report. In addition, we propose to require that the NDA
holder report the date the authorized generic drug ceased being
distributed to ensure that the list is as accurate and up-to-date as
possible. The first annual report submitted after implementation of
this regulation must provide information regarding any authorized
generic drug that was marketed during the time period covered by an
annual report submitted after January 1, 1999. When information is
included in an annual report about an authorized generic drug, we would
require that a copy of that portion of the annual report be sent to a
central office in the agency that will compile the list and update it
quarterly. This proposed rule assumes that the copy of the relevant
portion of the annual report may currently be submitted in any number
of formats (e.g., a paper copy, a PDF document on a computer disc).
Current capabilities do not permit direct electronic submission through
a Web-based system. However, FDA is committed to adapting its business
practices to evolving technology, including using the significant
advancements in Web-based, electronic systems. We anticipate that, in
future rulemakings, Web-based submission of annual reports will
eventually be required. In anticipation of that future change, this
proposed rule provides that once an electronic submission format is
adopted for annual reports, the submission to the agency of the
information required under this regulation will also be required in
that electronic format. We anticipate that when such a change is
implemented, future guidance will address any technical questions
related to such submissions.
II. Additional Information
This proposed rule is a companion to the direct final rule
published elsewhere in this issue of the Federal Register. This
companion proposed rule and the direct final rule are identical in
substance. This companion proposed rule will provide the procedural
framework to proceed with standard notice-and-comment rulemaking in the
event the direct final rule receives significant adverse comment and is
withdrawn. The comment period for the companion proposed rule runs
concurrently with the comment period of the direct final rule. Any
comments received under the companion proposed rule will be treated as
comments regarding the direct final rule and vice versa.
A significant adverse comment is one that explains why the rule
would be inappropriate, including challenges to the rule's underlying
premise or approach, or would be ineffective or unacceptable without
change. A comment recommending a rule change in addition to this rule
will not be considered a significant adverse comment unless the comment
states why this rule would be ineffective without the additional
change.
If no significant adverse comment is received in response to the
direct final rule, no further action will be taken related to the
companion proposed rule. Instead, we will publish a confirmation notice
within 30 days after the comment period ends. We intend the direct
final rule to become effective 30 days after publication of the
confirmation notice.
If we receive significant adverse comments, we will withdraw the
direct final rule. We will proceed to respond to all the comments
received regarding the direct final rule, treating those comments as
comments to this proposed rule. The agency will address the comments in
the subsequent final rule. We will not provide additional opportunity
for comment. If we receive
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a significant adverse comment which applies to part of the rule and
that part may be severed from the remainder of the rule, we may adopt
as final those parts of the rule that are not the subject of
significant adverse comment.
For additional background information, see the corresponding direct
final rule published elsewhere in this issue of the Federal Register.
All persons who may wish to comment should review the complete
rationale for this amendment set out in the preamble of the direct
final rule.
III. Environmental Impact
We have carefully considered, under 21 CFR part 25, the potential
environmental effects of this action. We have concluded that this
action will not have a significant impact on the human environment and
that an environmental impact statement is not required.
IV. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agency believes that
this proposed rule is not a significant regulatory action as defined by
the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because this proposed rule imposes only minimal
regulatory obligations, the agency certifies that the proposed rule
will not have a significant economic impact on a substantial number of
small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $130 million, using the most current (2007) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
The only costs of this proposed rule are associated with the
Paperwork Reduction Act burden, described in section V of this
document. If we assume an average hourly wage plus benefits of $56 for
the reporting personnel, the annual cost is about $29,000 ($56 per hour
x 520 hours).
V. The Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A
description of these provisions is given with an estimate of the annual
reporting and recordkeeping burden in Table 1 of this document.
Included in the estimate is the time for reviewing instructions,
searching existing data sources, gathering and maintaining the data
needed, and completing and reviewing each collection of information.
FDA invites comments on the following: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Applications for FDA Approval to Market a New Drug;
Postmarketing Reports; Reporting Information About Authorized Generic
Drugs.
Description: This rulemaking requires the holder of an NDA to
notify the agency if an authorized generic drug is marketed by clearly
including this information in annual reports in an easily accessible
place and by sending a copy of the relevant portion of the annual
reports to a central office. We are taking this action as part of our
implementation of FDAAA, which requires that FDA publish a list of all
authorized generic drugs included in an annual report after January 1,
1999, and that the agency update the list quarterly. We plan to publish
this list on the Internet and to notify relevant Federal agencies that
the list has been published and will be updated.
Description of Respondents: Current holders of an NDA under which
an authorized generic drug was marketed during the time period covered
by an annual report submitted after January 1, 1999.
Table 1.--Estimated Annual Reporting Burden\1\
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Number of Annual Frequency Total Annual Hours Per
21 CFR 314.81(b)(2)(ii)(b) Respondents per Response Responses Response Total Hours
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Authorized generic drug information in the first 60 6.7 400 1 hour 400
annual report submitted after the implementation of
Sec. 314.81(b)(2)(ii)(b)
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Authorized generic drug information submitted in each 60 6.7 400 15 minutes 100
subsequent annual report
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The submission of a copy of that portion of each 60 6.7 400 3 minutes 20
annual report containing authorized generic drug
information
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
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During the past several years, FDA has reviewed a small sample of
annual reports it has received under Sec. 314.81(b)(2) to discern
whether an authorized generic drug is being marketed by the NDA holder.
Based on information learned from this review and based on the number
of annual reports the agency currently receives under Sec.
314.81(b)(2),\1\ we estimate that, after the implementation of Sec.
314.81(b)(2)(ii)(b), we will receive approximately 400 annual reports
containing the information required under Sec. 314.81(b)(2)(ii)(b) for
authorized generic drugs that were marketed during the time period
covered by an annual report submitted after January 1, 1999. Based on
the number of sponsors that currently submit all annual reports, we
estimate that approximately 60 sponsors will submit these 400 annual
reports with authorized generics. As indicated in Table 1 of this
document, we are estimating that the same number of annual reports will
be submitted each subsequent year from the same number of sponsors
containing the information required under Sec. 314.81(b)(2)(ii)(b),
and that the same number of copies of that portion of each annual
report containing the authorized generic drug information will be
submitted from the same number of sponsors. Concerning the hours per
response, based on our estimate of 40 hours to prepare each annual
report currently submitted under Sec. 314.81(b)(2),\2\ we estimate
that sponsors will need approximately 1 hour to prepare the information
required under Sec. 314.81(b)(2)(ii)(b) for each authorized generic
drug that was marketed during the time period covered by an annual
report submitted after January 1, 1999, approximately 15 minutes to
prepare the information required under Sec. 314.81(b)(2)(ii)(b) for
each subsequent annual report, and approximately 3 minutes to submit to
FDA a copy of that portion of each annual report containing the
authorized generic drug information.
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\1\ During fiscal year 2006, the Center for Drug Evaluation and
Research received 2,569 annual reports under Sec. 314.81(b)(2) from
374 sponsors.)
\2\ See the Federal Register of January 4, 2008 (73 FR 865).
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The information collection provisions of this proposed rule have
been submitted to OMB for review. Interested persons are requested to
fax comments regarding information collection by October 29, 2008, to
the Office of Information and Regulatory Affairs, OMB. To ensure that
comments on information collection are received, OMB recommends that
written comments be faxed to the Office of Information and Regulatory
Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-6974.
VI. Legal Authority
The Federal Food, Drug, and Cosmetic Act (the act), as amended by
the Food and Drug Administration Amendments Act of 2007 (FDAAA),
provides authority for FDA to issue this proposed rule. Section 505(t)
of the act (21 U.S.C. 355(t); FDAAA section 920) requires that FDA
publish a complete list of all authorized generic drugs included in an
annual report submitted to the agency after January 1, 1999, and to
update that list quarterly. In addition, section 701(a) of the act (21
U.S.C. 371(a)) provides general authority for FDA to issue regulations
for the efficient enforcement of the act. This proposed rule would
amend FDA's existing regulations regarding annual reports in order to
ensure that the information necessary for the agency to fulfill its
obligation under section 505(t) is clearly reported.
VII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the rule does not contain policies that have substantial direct effects
on the States, on the relationship between the National Government and
the States, or on the distribution of power and responsibilities among
the various levels of government. Accordingly, the agency has concluded
that the rule does not contain policies that have federalism
implications as defined in the Executive order and, consequently, a
federalism summary impact statement is not required.
VIII. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
This comment period runs concurrently with the comment period for the
direct final rule; any comments received will be considered as comments
regarding the direct final rule. Submit a single copy of electronic
comments or two paper copies of any mailed comments, except that
individuals may submit one paper copy. Comments are to be identified
with the docket number found in brackets in the heading of this
document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
Please note that on January 15, 2008, the FDA Division of Dockets
Management Web site transitioned to the Federal Dockets Management
System (FDMS). FDMS is a Government-wide, electronic docket management
system. Electronic comments or submissions will be accepted by FDA only
through FDMS at http://www.regulations.gov.
List of Subjects in 21 CFR Part 314
Administrative practice and procedure, Confidential business
information, Drugs, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 314 be amended as follows:
PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG
1. The authority citation for 21 CFR part 314 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 356a,
356b, 356c, 371, 374, 379e.
2. Section 314.3 is amended in paragraph (b) by adding the
following definition for authorized generic drug in alphabetical order:
Sec. 314.3 Definitions.
* * * * *
(b) * * *
Authorized generic drug means a listed drug, as defined in this
section, that has been approved under section 505(c) of the act and is
marketed, sold, or distributed directly or indirectly to retail class
of trade with labeling, packaging (other than repackaging as the listed
drug in blister packs, unit doses, or similar packaging for use in
institutions), product code, labeler code, trade name, or trade mark
that differs from that of the listed drug.
* * * * *
3. Section 314.81 is amended by redesignating paragraph (b)(2)(ii)
as paragraph (b)(2)(ii)(a) and by adding new paragraph (b)(2)(ii)(b) as
follows:
Sec. 314.81 Other postmarketing reports.
* * * * *
(b) * * *
(2) * * *
(ii) * * *
(b) Authorized generic drugs. If applicable, the date each
authorized generic drug (as defined in Sec. 314.3) entered the market,
the date each authorized generic drug ceased being distributed, and the
corresponding trade or brand name. Each dosage form and/or strength is
a different authorized generic drug and should be listed separately.
The first annual report
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submitted on or after February 11, 2009, must include the information
listed in this paragraph for any authorized generic drug that was
marketed during the time period covered by an annual report submitted
after January 1, 1999. If information is included in the annual report
with respect to any authorized generic drug, a copy of that portion of
the annual report must be sent to the Food and Drug Administration,
Center for Drug Evaluation and Research, Office of Pharmaceutical
Science, 10903 New Hampshire Ave., Bldg. 51, rm. 4183, Silver Spring,
MD 20993-0002 and marked ``Authorized Generic Submission'' or, if FDA
has required that annual reports be submitted in an electronic format,
the information required by this section must also be submitted in the
electronic format.
* * * * *
Dated: September 16, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-22829 Filed 9-26-08; 8:45 am]
BILLING CODE 4160-01-S