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###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. FDA-2021-D-0398]

# 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 entitled “Human Gene Therapy Products Incorporating Human Genome Editing; Guidance for Industry.” The guidance document provides recommendations to sponsors developing human gene therapy products incorporating genome editing (GE) of human somatic cells. Specifically, the guidance provides recommendations regarding information that should be provided in an investigational new drug (IND) application to assess the safety and quality of the investigational GE product, including information on product design, product manufacturing and testing, nonclinical safety assessment, and clinical trial design. The guidance announced in this notice finalizes the draft guidance of the same title dated March 2022.

# DATES:

                        The announcement of the guidance is published in the                         **Federal Register**                         on January 30, 2024.                    

# 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-2021-D-0398 for “Human Gene Therapy Products Incorporating Human Genome Editing.” 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 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 guidance may also be obtained by mail by calling CBER at 1-800-835-4709 or 240-402-8010. See                           ( print page 5914)                        the                     **SUPPLEMENTARY INFORMATION**                     section for electronic access to the 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 document entitled “Human Gene Therapy Products Incorporating Human Genome Editing; Guidance for Industry.” The guidance document provides recommendations to sponsors developing human gene therapy products incorporating GE of human somatic cells. Specifically, the guidance provides recommendations regarding information that should be provided in an IND application to assess the safety and quality of the investigational GE product, including information on product design, product manufacturing and testing, nonclinical safety assessment, and clinical trial design.

                    In the                     **Federal Register**                     of March 16, 2022 (87 FR 14897), FDA announced the availability of the draft guidance of the same title dated March 2022. FDA received numerous comments on the draft guidance and those comments were considered as the guidance was finalized. Changes to the guidance include clarifying the recommendations for GE components used only once (for example, in the manufacture of a master cell bank), expectations for potency assays, considerations for nonclinical studies with respect to potential for off-target toxicity, and applicability of accelerated approval to GE products. In addition, editorial changes were made to improve clarity. The guidance announced in this notice finalizes the draft guidance dated March 2022.                

                    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 Development of Chimeric Antigen Receptor (CAR) T Cell Products; Guidance for Industry.”                

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 “Human Gene Therapy Products Incorporating Human Genome Editing.” 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. 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 (44 U.S.C. 3501-3521). 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 parts 210 and 211 have been approved under OMB control number 0910-0073; 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 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: January 24, 2024.

Lauren K. Roth,

Associate Commissioner for Policy.

[FR Doc. 2024-01788 Filed 1-29-24; 8:45 am]

BILLING CODE 4164-01-P