[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

[[Page 56531]]

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.


[[Page 56532]]

    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

[[Page 56533]]

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