[Federal Register Volume 79, Number 43 (Wednesday, March 5, 2014)]
[Notices]
[Pages 12511-12512]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-04811]



[[Page 12511]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0283]


Guidance for Industry on Chemistry, Manufacturing, and Controls 
Postapproval Manufacturing Changes To Be Documented 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 guidance for industry entitled ``CMC Postapproval 
Manufacturing Changes To Be Documented in Annual Reports.'' This 
guidance provides recommendations to holders of new drug applications 
(NDAs) and abbreviated new drug applications (ANDAs) regarding the 
types of changes to be documented in annual reports. Specifically, the 
guidance describes chemistry, manufacturing, and controls (CMC) 
postapproval manufacturing changes that FDA has determined will likely 
have a minimal potential to have an adverse effect on product quality 
and, therefore, should be documented by applicants in an annual report. 
(The guidance excludes positron emission tomography drug products.)

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of this 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 
guidance document.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Robert Iser, Office of Pharmaceutical 
Science, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 4178, Silver 
Spring, MD 20993-0002, 301-796-2400, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``CMC Postapproval Manufacturing Changes To Be Documented in 
Annual Reports.'' This guidance provides recommendations to holders of 
NDAs and ANDAs regarding the types of CMC postapproval manufacturing 
changes that FDA has determined will likely have a minimal potential to 
have an adverse effect on product quality, and therefore, should be 
documented by applicants in an annual report under Sec.  314.70(d) (21 
CFR 314.70(d)).
    On June 25, 2010 (75 FR 36421), FDA announced the availability of 
the draft version of this guidance. The public comment period closed on 
September 23, 2010. A number of comments were received from the public, 
all of which the Agency considered carefully as it finalized the 
guidance and made appropriate changes. Any changes to the guidance were 
minor and made to clarify statements in the draft guidance.
    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 low risk to 
the quality of the product and do not need to be submitted in 
supplements.
    Based on its risk-based evaluation, FDA developed a list (attached 
as an appendix to the guidance) to provide additional current 
recommendations to companies regarding some postapproval manufacturing 
changes for NDAs and ANDAs that may be considered to have a minimal 
potential to have an adverse effect on product quality, and, therefore, 
may be classified as a change to be documented in the next annual 
report (i.e., notification of a change after implementation) rather 
than in a supplement.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on CMC postapproval manufacturing changes to 
be documented in annual reports. 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 either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of 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, and will be posted to the docket at http://www.regulations.gov.

III. Paperwork Reduction Act of 1995

    This guidance contains collections of information 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 collections 
of information have been approved under OMB control number 0910-0758. 
This guidance also refers to the following previously approved 
collections of information: (1) The submission of supplements to FDA 
for certain changes to an approved application in accordance with Sec.  
314.70 and 21 CFR 314.71; (2) the submission of annual reports to FDA 
(Form FDA 2252) in accordance with Sec.  314.81(b)(2) (21 CFR 
314.81(b)(2)); (3) the submission of supplements to an approved ANDA 
for changes that require FDA approval; and (4) other post-marketing 
reports for ANDAs in accordance with 21 CFR 314.98(c), of which the 
estimate for annual reports is included under Sec.  314.81(b)(2). FDA 
currently has OMB approval for these collections of information under 
OMB control number 0910-0001.

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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: February 27, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-04811 Filed 3-4-14; 8:45 am]
BILLING CODE 4160-01-P