[Federal Register Volume 88, Number 134 (Friday, July 14, 2023)]
[Notices]
[Pages 45222-45223]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-14917]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-2436]


Manufacturing Changes and Comparability for Human Cellular and 
Gene Therapy Products; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft document entitled ``Manufacturing Changes 
and Comparability for Human Cellular and Gene Therapy Products; Draft 
Guidance for Industry.'' The management of manufacturing changes 
presents many challenges for human cellular therapy or gene therapy 
(CGT) products due to the complexity of these products. The draft 
guidance provides sponsors of Investigational New Drug Applications 
(INDs) and applicants of Biologics License Applications (BLAs) for CGT 
products, with recommendations regarding product comparability and the 
management of manufacturing changes for investigational and licensed 
CGT products. The purpose of this draft guidance is to provide FDA's 
current thinking on management and reporting of manufacturing changes 
for CGT products based on a life-cycle approach, and comparability 
studies to assess the effect of manufacturing changes on product 
quality.

DATES: Submit either electronic or written comments on the draft 
guidance by September 12, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-2023-D-2436 for ``Manufacturing Changes and Comparability for Human 
Cellular and Gene Therapy Products; Draft Guidance for Industry.'' 
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 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 the draft guidance to 
the Office of Communication, Outreach and Development, Center for 
Biologics Evaluation and Research (CBER), 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 the office in 
processing your requests. The draft guidance may also be obtained by 
mail by calling CBER at 1-800-835-4709 or 240-402-8010. See the 
SUPPLEMENTARY INFORMATION section for electronic access to the draft 
guidance document.

FOR FURTHER INFORMATION CONTACT: Phillip Kurs, 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 draft document entitled 
``Manufacturing Changes and Comparability for Human Cellular and Gene 
Therapy Products; Draft Guidance for Industry.'' The management of 
manufacturing changes presents many challenges for human CGT products 
due to the complexity of these products. The draft guidance provides 
sponsors of INDs and applicants who intend to submit or currently hold 
BLAs for CGT products, with recommendations on product comparability 
and the management of manufacturing changes for investigational and 
licensed CGT products, considering the unique challenges that apply to 
these products.

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While existing guidances provide general principles and recommendations 
regarding comparability studies and management of manufacturing changes 
for biological products, they generally do not address specific CGT 
product challenges. The purpose of this draft guidance is to provide 
FDA's current thinking on: (1) management and reporting of 
manufacturing changes for CGT products based on a life-cycle approach 
and (2) comparability studies to assess the effect of manufacturing 
changes on CGT product quality.
    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 current thinking of FDA on 
``Manufacturing Changes and Comparability for Human Cellular and Gene 
Therapy Products.'' 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 part 211 have been approved under OMB control 
number 0910-0139; the collections of information in 21 CFR part 312 
have been approved under OMB control number 0910-0014; and the 
collections of information in 21 CFR 601.2 and 601.12 have been 
approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at 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: July 10, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-14917 Filed 7-13-23; 8:45 am]
BILLING CODE 4164-01-P


