Direct Final Rule: Applications for Food and Drug Administration Approval 
to Market a New Drug; Postmarketing Reports; Reporting Information About 
Authorized Generic Drugs

Federal Register: September 29, 2008 (Volume 73, Number 189)             
                  Page 56487-56491

AGENCY: Food and Drug Administration, HHS.

ACTION: Direct final rule.

SUMMARY: The Food and Drug Administration (FDA) is amending its 
regulations to require that the holder of a new drug application (NDA) 
submit certain information regarding authorized generic drugs in an 
annual report. 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. We are using direct final rulemaking for this action 
because the agency expects that there will be no significant adverse 
comment on the rule. In the proposed rule section of this issue of the 
Federal Register, we are concurrently proposing and soliciting comments 
on this rule. If significant adverse comments are received, we will 
withdraw this final rule and address the comments in a subsequent final 
rule. FDA will not provide additional opportunity for comment.

DATES: This direct final rule is effective February 11, 2009. Submit 
written or electronic comments on or before December 15, 2008. If we 
receive no timely significant adverse comments, we will publish a 
notice in the Federal Register before January 12, 2009, confirming the 
effective date of the direct final rule. If we receive any timely 
significant adverse comments, we will publish a notice of significant 
adverse comment in the Federal Register withdrawing this direct final 
rule before February 11, 2009.

[[Page 56488]]


ADDRESSES: You may submit comments, identified by Docket No. FDA-2008-
N-0341, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following way:
     Federal eRulemaking Portal: 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov 
and insert the 
docket number, 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

    On September 27, 2007, the President signed into law FDAAA (Public 
Law 110-85, 121 Stat. 823). Section 920 of FDAAA adds new section 
505(t) to the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 
355(t)) and requires that FDA take the following actions:
     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, consisting of the drug trade name, the 
brand company manufacturer, and the date the authorized generic drug 
entered the market;
     Update the list quarterly; and
     Notify relevant Federal agencies, including the Centers 
for Medicare and Medicaid Services and the Federal Trade Commission, 
that the list has been published and will be updated quarterly.
    For purposes of publishing the list, section 505(t)(3) of the act 
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.''
    Currently, there is no requirement that an NDA holder specifically 
report that it is marketing an ``authorized generic drug.'' NDA holders 
are required to include information about distribution or certain 
changes to manufacturing or labeling in annual reports, which may 
indicate that an authorized generic is being marketed. However, annual 
reports may not include all the information necessary for FDA to 
publish the list required by FDAAA. For example, sponsors rarely 
include the date the authorized generic entered the market.
    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 adding a requirement that annual reports 
specifically and clearly include the information we are required to 
report. In addition, we are requiring 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.
    There are currently 15 divisions in FDA that receive annual reports 
for over 2,200 active NDAs. When information is included in an annual 
report about an authorized generic drug, we are requiring 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.

II. Direct Final Rulemaking

    We have determined that the subject of this rulemaking is suitable 
for a direct final rule. FDA expects this amendment to be 
noncontroversial, and the agency does not anticipate receiving any 
significant adverse comments on this rule. We have determined that 
publishing a direct final rule is the most appropriate method to meet 
the requirement, under section 505(t) of the act, that the agency 
publish a list of all authorized generic drugs.
    If we receive no significant adverse comment, we will publish a 
document in the Federal Register confirming the effective date of the 
direct final rule. 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 a 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 timely significant adverse comments are received, 
we will publish a notice of significant adverse comment in the Federal 
Register withdrawing this direct final rule within 30 days after the 
comment period ends.
    Elsewhere in this issue of the Federal Register, we are publishing 
a companion proposed rule, identical in substance to this direct final 
rule, that provides a procedural framework from which to proceed with 
standard notice-and-comment rulemaking in the event the direct final 
rule is withdrawn because of significant adverse comment. The comment 
period for the direct final rule runs concurrently with that of the 
companion proposed rule. Any comments received under the companion 
proposed rule will be treated as comments regarding the direct final 
rule. Likewise, significant adverse comments submitted to the direct 
final rule will be considered as comments to the companion proposed 
rule, and we will consider those comments in developing a final rule. 
We will not provide additional opportunity for comment on the companion 
proposed rule.
    If a significant adverse comment applies to part of this 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 a 
significant adverse comment. A full description of our policy on direct 
final

[[Page 56489]]

rule procedures may be found in a guidance document published in the 
Federal Register of November 21, 1997 (62 FR 62466).

III. Description of the Direct Final Rule

    We are defining the term ``authorized generic drug'' as a listed 
drug (as defined in Sec.  314.3 (21 CFR 314.3)) 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 either 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.
    We are amending our regulations in Sec.  314.81 (21 CFR 314.81) to 
require that an NDA holder specifically report that it has marketed an 
authorized generic drug during the applicable time period. Section 
314.81(b)(2) requires that an NDA holder submit an annual report within 
60 days of the anniversary date of approval of an NDA for every NDA it 
holds. We are amending Sec.  314.81 by redesignating paragraph 
(b)(2)(ii) regarding distribution data, as paragraph (b)(2)(ii)(a), and 
adding a new paragraph (b)(2)(ii)(b) regarding marketing of authorized 
generic drugs. This new paragraph states that, if an authorized generic 
drug was marketed under an NDA, or ceased to be marketed, during the 
reporting year, the annual report must list the date each authorized 
generic drug 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 submitted 
after implementation of this regulation must include the required 
marketing information 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 the portion of the annual report 
with that information 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.'' This final 
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 final 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.

IV. 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 direct final 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 direct final 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.

V. 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.

VI. Analysis of Impacts

    FDA has examined the impacts of the direct final 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 direct final 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 direct final rule imposes only minimal 
regulatory obligations, the agency certifies that the direct 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 
direct final rule to result in any 1-year expenditure that would meet 
or exceed this amount.
    The only costs of this direct final rule are associated with the 
Paperwork Reduction Act burden, described in section VII 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).

VII. The Paperwork Reduction Act of 1995

    This direct final 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). The 
title, description, and respondent description of the information 
collection provisions are shown 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.
    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

[[Page 56490]]

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\
----------------------------------------------------------------------------------------------------------------
       21 CFR             Number of        Annual Frequency       Total Annual     Hours per
 314.81(b)(2)(ii)(b)     Respondents         per Response          Responses        Response      Total Hours
----------------------------------------------------------------------------------------------------------------
Authorized generic                   60                   6.7                400  1 hour                     400
 drug information in
 the first annual
 report submitted
 after the
 implementation of
 Sec.
 314.81(b)(2)(ii)(b)
----------------------------------------------------------------------------------------------------------------
Authorized generic                   60                   6.7                400  15 minutes                 100
 drug information
 submitted in each
 subsequent annual
 report
----------------------------------------------------------------------------------------------------------------
The submission of a                  60                   6.7                400  3 minutes                   20
 copy of that
 portion of each
 annual report
 containing
 authorized generic
 drug information
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

VIII. Federalism

    FDA has analyzed this direct final 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.

IX. Request for Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
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://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov. 

List of Subjects in 21 CFR Part 314

    Administrative practice and procedure, Confidential business 
information, Drugs, Reporting and recordkeeping requirements.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
314 is amended as follows:

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

0
1. The authority citation for 21 CFR part 314 continues to read as 
follows:


[[Page 56491]]


    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 356a, 
356b, 356c, 371, 374, 379e.

0
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.
* * * * *

0
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 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. E8-22833 Filed 9-26-08; 8:45 am]

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