2024-09287. Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Draft Guidance for Industry; Availability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.

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of a draft document entitled “Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Draft Guidance for Industry.”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 The draft guidance document provides sponsors of allogeneic cell-based medical products recommendations for determining the appropriate cell safety testing to support an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Submit either electronic or written comments on the draft guidance by July 29, 2024 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.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.

• 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 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.