[Federal Register Volume 89, Number 84 (Tuesday, April 30, 2024)]
[Notices]
[Pages 34251-34253]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-09287]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-1243]


Safety Testing of Human Allogeneic Cells Expanded for Use in 
Cell-Based Medical Products; Draft Guidance for Industry; Availability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 ``Safety Testing of Human 
Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Draft 
Guidance for Industry.'' Allogeneic cells of human origin may be 
expanded in culture to manufacture medical products consisting of live 
cells, inactivated cells, cell lysates, or other cell-based materials 
such as cell-derived particles. The draft guidance document provides 
sponsors of allogeneic cell-based medical products recommendations for 
determining the appropriate cell safety testing to support an 
investigational new drug application (IND) or a biologics license 
application (BLA). Cell safety testing should be based on a risk 
analysis that considers the expansion potential of the cells, the 
reagents that are used to expand the cells in culture, and the number 
of individuals the cell-based medical product is capable of treating.

DATES: Submit either electronic or written comments on the draft 
guidance by July 29, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2024-D-1243 for ``Safety Testing of Human Allogeneic Cells Expanded 
for Use in Cell-Based Medical 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.

[[Page 34252]]

     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: Tami Belouin, 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 
``Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-
Based Medical Products; Draft Guidance for Industry.'' Allogeneic cells 
of human origin may be expanded in culture to manufacture medical 
products consisting of live cells, inactivated cells, cell lysates, or 
other cell-based materials such as cell-derived particles. The draft 
guidance document provides sponsors of allogeneic cell-based medical 
products recommendations for determining the appropriate cell safety 
testing to support an IND or a BLA. Cell safety testing should be based 
on a risk analysis that considers the expansion potential of the cells, 
the reagents that are used to expand the cells in culture, and the 
number of individuals the cell-based medical product is capable of 
treating. This guidance does not address the measurement or analysis of 
cell characteristics that may be relevant to biological activity.
    Viral and microbial contamination is a potential risk for all cell-
based medical products, especially when the cells are cultured 
extensively during manufacturing. Contamination may be present in the 
source cells, or the cells may become contaminated with adventitious 
agents during manufacturing. In addition, genomic changes that result 
in tumorigenic cells can occur during extensive culture.
    The purpose of this draft guidance is to provide guidance on safety 
testing to assist manufacturers in addressing the requirements of 21 
CFR 610.18(c)(1) and 312.23(a)(7), and other relevant regulations, as 
applicable, with respect to human allogeneic cells expanded for use in 
cell-based medical products. FDA's recommendations for cell safety 
testing reflect a risk-based approach that takes into consideration 
both the specific characteristics of the cells and their proposed use.
    The recommendations in this draft guidance apply to cultured 
allogeneic cells, including cell banks, that are sources of the 
intended constituents of the final drug product, as well as combination 
products that contain an allogeneic cell or cell-based biologic 
constituent part in combination with a drug and/or device. The 
recommendations in this draft guidance also apply to genetically 
modified allogeneic cells that have been transduced with viral and/or 
plasmid vectors, and cells that have undergone genome editing. This 
guidance does not apply to cell substrates that are used during 
manufacturing of non-cell-based products such as viruses, gene therapy 
vectors, or recombinant proteins.
    The draft guidance, when finalized, is intended to supplement the 
following two final guidances: ``Chemistry, Manufacturing, and Control 
(CMC) Information for Human Gene Therapy Investigational New Drug 
Applications (INDs); Guidance for Industry'' dated January 2020, and 
``Guidance for FDA Reviewers and Sponsors: Content and Review of 
Chemistry, Manufacturing, and Control (CMC) Information for Human 
Somatic Cell Therapy Investigational New Drug Applications (INDs)'' 
dated April 2008.
    Elsewhere in this issue of the Federal Register, FDA is announcing 
the availability of another human gene therapy final guidance document 
entitled ``Considerations for the Use of Human-and Animal-Derived 
Materials and Components in the Manufacture of Cell and Gene Therapy 
and Tissue-Engineered Medical Products; Draft Guidance for Industry.''
    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 ``Safety 
Testing of Human Allogeneic Cells Expanded for Use in Cell-Based 
Medical 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 draft guidance contains no collection of information, it 
does refer to previously approved FDA collections of information. The 
previously approved collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information 
in 9 CFR 113.47 and 113.53 have been approved under OMB control number 
0579-0013; the collections of information in 21 CFR part 312 have been 
approved under OMB control number 0910-0014; the collections of 
information in 21 CFR part 601 have been approved under OMB control 
number 0910-0338; the collections of information in 21 CFR part 610 
have been approved under OMB control number 0910-0139; and the 
collections of information in 21 CFR part 1271 have

[[Page 34253]]

been approved under OMB control number 0910-0543.

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: April 25, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-09287 Filed 4-29-24; 8:45 am]
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