[Federal Register Volume 86, Number 235 (Friday, December 10, 2021)]
[Notices]
[Pages 70508-70509]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-26734]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-2802]


Chemistry, Manufacturing, and Controls Postapproval Manufacturing 
Changes for Specified Biological Products To Be Documented in Annual 
Reports; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``CMC 
Postapproval Manufacturing Changes for Specified Biological Products to 
Be Documented in Annual Reports.'' This guidance provides 
recommendations to holders of biologics license applications (BLAs) for 
specified biological products 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 generally considers to have a minimal potential to 
have an adverse effect on the identity, strength, quality, purity, or 
potency of the product as they may relate to the safety or 
effectiveness of the product. Under FDA regulations, such minor changes 
in the product, production process, quality controls, equipment, 
facilities, or responsible personnel must be documented by applicants 
in an annual report. The guidance finalizes the draft guidance of the 
same title dated August 2017.

DATES: The announcement of the guidance is published in the Federal 
Register on December 10, 2021.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2017-D-2802 for ``CMC Postapproval Manufacturing Changes for 
Specified Biological Products To Be Documented in Annual Reports.'' 
Received comments will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not

[[Page 70509]]

in the body of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002; or to the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, 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.

FOR FURTHER INFORMATION CONTACT: Michail Alterman, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 4245, Silver Spring, MD 20993, 240-402-
9355, or Stephen Ripley, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``CMC Postapproval Manufacturing Changes for Specified 
Biological Products To Be Documented in Annual Reports.'' Applicants 
must notify FDA of a change to an approved BLA in accordance with all 
statutory and regulatory requirements--including section 506A of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356a) and 
Sec.  601.12 (21 CFR 601.12). Section 506A of the FD&C Act provides 
requirements for making and reporting manufacturing changes to an 
approved application or license and for distributing a drug made with 
such changes. Under Sec.  601.12, each postapproval change in the 
product, production process, quality controls, equipment, facilities, 
or responsible personnel established in an approved BLA is categorized 
into one of three reporting categories:
     Major change: Applicants must submit and receive FDA 
approval of a supplement to the BLA before the product produced with 
the manufacturing change is distributed.
     Moderate change: Applicants must submit a supplement at 
least 30 days before the product is distributed or, in some cases, the 
product may be distributed immediately upon FDA's receipt of the 
supplement.
     Minor change: Applicants may proceed with the change but 
must notify FDA of the change in an annual report.
    This guidance provides recommendations for reporting certain 
changes in an annual report. It discusses the contents of an annual 
report notification and lists examples of postapproval manufacturing 
changes for BLAs that FDA generally considers to have a minimal 
potential to have an adverse effect on the identity, strength, quality, 
purity, or potency of the product as they may relate to the safety or 
effectiveness of the product.
    This guidance finalizes the draft guidance of the same title issued 
on August 9, 2017 (82 FR 37232) in the Federal Register. FDA considered 
comments received on the draft guidance as the guidance was finalized. 
Based on comments received, FDA updated the guidance with additional 
manufacturing examples and made editorial changes to improve clarity.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on ``CMC Postapproval Manufacturing Changes for 
Specified Biological Products To Be Documented in Annual Reports.'' It 
does not establish any rights for any person and is not binding on FDA 
or the public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR 601.12 have been approved under OMB control 
number 0910-0338; and the collections of information in 21 CFR parts 
210 and 211 have been approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: December 6, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-26734 Filed 12-9-21; 8:45 am]
BILLING CODE 4164-01-P


