[Federal Register Volume 75, Number 122 (Friday, June 25, 2010)]
[Notices]
[Pages 36421-36423]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-15415]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-D-0283]
Draft Guidance for Industry on Chemistry, Manufacturing, and
Controls Postapproval Manufacturing Changes Reportable in Annual
Reports; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``CMC
Postapproval Manufacturing Changes Reportable in Annual Reports.'' This
draft guidance provides recommendations to holders of new drug
applications (NDAs) and abbreviated new drug applications (ANDAs)
regarding the types of changes that may be reported in annual reports.
Specifically, the draft guidance describes chemistry, manufacturing,
and controls (CMC) postapproval manufacturing changes that FDA has
determined will likely present minimal potential to have adverse
effects on product quality and, therefore, may be reported by
applicants in an annual report. (The draft guidance excludes positron
emission tomography (PET) drug products.)
DATES: Although you can comment on any guidance at any time (see 21
CFR 10.115(g)(5)), to ensure that the agency considers your comment on
this draft guidance before it begins work on the final version of the
guidance, submit either electronic or written comments on the draft
guidance by September 23, 2010.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments, including comments
regarding the proposed collection of information, to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Jon Clark, Center for Drug Evaluation
and Research, Food and Drug Administration, Bldg. 51, rm. 4178, 10903
New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-2400.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``CMC Postapproval Manufacturing Changes Reportable in Annual
Reports.'' This draft guidance provides recommendations to holders of
NDAs and ANDAs regarding the types of CMC postapproval manufacturing
changes that FDA has determined will likely present minimal potential
to have adverse effects on product quality, and therefore, may be
reported by applicants in an annual report under Sec. 314.70 (21 CFR
314.70).
In its September 2004 final report, ``Pharmaceutical Current Good
Manufacturing Practices (CGMPs) for the 21st Century--A Risk-Based
Approach'' (Pharmaceutical Product Quality Initiative, http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm137175.htm), FDA stated that to keep pace with the many advances in
quality management practices in manufacturing and to enable the agency
to more effectively allocate its limited regulatory resources, FDA
would implement a cooperative, risk-based approach for regulating
pharmaceutical manufacturing. As part of this approach, FDA determined
that to provide the most effective public health protection, its CMC
regulatory review should be based on an understanding of product risk
and how best to manage this risk.
The number of CMC manufacturing supplements for NDAs and ANDAs has
continued to increase over the last several years. In connection with
FDA's Pharmaceutical Product Quality Initiative and its risk-based
approach to CMC review, FDA has evaluated the types of changes that
have been submitted in CMC postapproval manufacturing supplements and
determined that many of the changes being reported present very low
risk to the quality of the product and do not need to be submitted in
supplements.
[[Page 36422]]
Based on this recent evaluation, FDA developed a list (attached as
an appendix to the draft guidance) to provide current recommendations
to companies regarding which postapproval manufacturing changes for
NDAs and ANDAs may be considered to have a minimal potential for an
adverse effect on the identity, strength, quality, purity, or potency
of the drug product and, therefore, may be classified as a change
reportable in an annual report (e.g., notification of a change after
implementation) rather than in a supplement.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the agency's current thinking on CMC
postapproval manufacturing changes reportable in annual reports for
NDAs and ANDAs. It does not create or confer any rights for or on any
person and does not operate to bind FDA or the public. An alternative
approach may be used if such approach satisfies the requirements of the
applicable statutes and regulations.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed comments. Identify
comments 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.
III. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act (44 U.S.C. 3501-3520) (the PRA),
Federal agencies must obtain approval from the Office of Management and
Budget (OMB) for each collection of information they conduct or
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3)
and 5 CFR 1320.3(c) and includes agency requests or requirements that
members of the public submit reports, keep records, or provide
information to a third party. Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day
notice in the Federal Register concerning each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing notice of the proposed
collection of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (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: CMC Postapproval Manufacturing Changes Reportable in Annual
Reports.
Description of Respondents: Respondents to this collection of
information are applicants of approved NDAs and ANDAs.
Burden Estimate: FDA is requesting public comment on estimates of
annual submissions from these respondents, as required by Sec. 314.70
and Sec. Sec. 314.71, 314.81(b)(2), and 314.97 (21 CFR 314.71,
314.81(b)(2), and 314.97) and described in this draft guidance.
Sections 314.70 and 314.71 require that supplements be submitted to FDA
for certain changes to an approved application. Section 314.81(b)(2)
requires that annual reports be submitted to FDA (Form FDA 2252).
Section 314.97 sets forth requirements for submitting supplements to an
approved ANDA for changes that require FDA approval. Section 314.98(c)
requires annual reports and other postmarketing reports for ANDAs. The
estimate for annual reports for ANDAs is included under Sec.
314.81(b)(2). Other postmarketing reports under Sec. 314.98(c) are not
implicated by this notice.
The draft guidance describes our current thinking on the
interpretation of these requirements. Part of the intent for this draft
guidance is to reduce the burden of reporting some manufacturing
changes. Currently, for postapproval changes considered to be major,
applicants of NDAs and ANDAs must submit and receive FDA approval of a
supplement before the product made with the manufacturing change is
distributed. If a change is considered to be moderate, an applicant
must submit a supplement at least 30 days before the product is
distributed or, in some cases, submit a supplement at the time of
distribution. If a change is considered to be minor, an applicant may
proceed with the change, but must notify FDA of the change in an annual
report. When a change is approved via a supplemental application, these
changes currently also must be reported in the annual report. The draft
guidance describes the types of postapproval changes that applicants of
NDAs and ANDAs currently submit in supplements to NDAs or ANDAs but
that, under the draft guidance, may now be reported only in annual
reports and do not need prior FDA approval. As a result, applicants
would no longer need to submit supplements for such changes.
FDA currently has OMB approval for the collection of information
entitled, ``Application for Food and Drug Administration Approval to
Market a New Drug'' (OMB Control Number 0910-0001). This collection of
information includes all information requirements imposed by the
regulations under part 314 (21 CFR part 314) on applicants who apply
for approval of an NDA or ANDA to market or change an approved
application. In particular, among other things, this collection of
information includes: (1) The submission of supplements to FDA for
certain changes to an approved application in accordance with
Sec. Sec. 314.70 and 314.71; (2) the submission of annual reports to
FDA (Form FDA 2252) in accordance with Sec. 314.81(b)(2); (3) the
submission of supplements to an approved ANDA for changes that require
FDA approval; and (4) other postmarketing reports for ANDAs in
accordance with Sec. 314.98(c), of which the estimate for annual
reports is included under Sec. 314.81(b)(2). Therefore, this
information collection includes the supplements to NDAs and ANDAs and
the annual reports for NDAs and ANDAs that are described in the draft
guidance.
Under the applicable regulations and the draft guidance, the
following change to the current approval by OMB under the PRA is
estimated: Supplements to NDAs under Sec. Sec. 314.70 and 314.71 and
supplements to ANDAs under Sec. 314.97. Although the submission of
supplements to NDAs and ANDAs is approved under OMB Control Number
0910-0001, the total number of supplements submitted per year is
estimated to be reduced based on the recommendations in the draft
guidance because certain changes submitted as supplements would now be
submitted in annual reports. Therefore, for such changes, the
information collection with respect to the submission of supplements
will be reduced. Because the number of supplements per year is
estimated to be reduced, the total number of hours for preparing
supplements is also estimated to be reduced.
[[Page 36423]]
Based on FDA's knowledge of supplements and annual reports to NDAs
and ANDAs, as well as the agency's familiarity with the time needed to
prepare supplements and annual reports, our estimates for this
information collection are as follows: The total number of supplements
submitted per year is estimated to be reduced based on the
recommendations in the draft guidance. Based on the number of CMC
manufacturing supplements received for NDAs and ANDAs during 2008, FDA
estimates that it will receive annually approximately 800 responses
under Sec. Sec. 314.70 and 314.71 for NDAs and approximately 2,075
responses under Sec. 314.97 for ANDAs. The number of annual
frequencies per response will decrease accordingly. FDA estimates that
approximately the same number of respondents will submit responses
under Sec. Sec. 314.70, 314.71, and 314.97 and each response will take
approximately the same amount of time to prepare as in the information
collection currently approved under OMB Control Number 0910-0001.
Table 1.--Estimated Annual Reporting Burden\1\
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Annual Frequency Total Annual Hours Per
21 CFR Section No. of Respondents per Response Responses Response Total Hours
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314.70 and 314.71 281 (same as 2.85 800 150 (same as 120,000
currently currently
approved) approved)
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314.97 215 (same as 9.65 2,075 80 (same as 166,000
currently currently
approved) approved)
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Total Hours 286,000
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
Therefore, the estimated annual reporting burden for this
information collection is 286,000 hours.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.
Dated: June 21, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-15415 Filed 6-24-10; 8:45 am]
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