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

###### Food and Drug Administration

          - [Docket No. FDA-2023-D-3900]

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice of availability.

      ( print page 67302)    

# SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Graft-versus-Host Diseases: Developing Drugs, Biological Products, and Certain Devices for Prevention or Treatment.” The purpose of this guidance is to assist sponsors in the clinical development of drugs, biological products, and certain devices for the prevention or treatment of acute graft-versus-host disease (aGVHD) or chronic graft-vs-host disease (cGVHD). Specifically, this guidance addresses FDA's current thinking regarding the overall clinical development program and critical design elements for early and late phase trials for the intended populations. This guidance focuses on clinical trial design, statistical analysis, or other issues specific to aGVHD or cGVHD, and it does not contain a discussion of the general principles regarding statistical analysis, clinical trial design, or drug development. Additionally, this guidance is not intended to provide advice on the technical aspects of therapeutic or cell-processing devices.

# DATES:

Submit either electronic or written comments on the draft guidance by November 28, 2023 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.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-3900 for “Graft-versus-Host Diseases: Developing Drugs and Biological Products for Prevention or Treatment.” 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 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; 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; or to the Office of Policy, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, 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 draft guidance document.                

# FOR FURTHER INFORMATION CONTACT:

Robert Le, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2124, Silver Spring, MD 20993, 240-402-8320, or Anne Taylor, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7256, Silver Spring, MD 20993, 240-402-5683.

# SUPPLEMENTARY INFORMATION:

## I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Graft-versus-Host Diseases: Developing Drugs, Biological Products, and Certain Devices for Prevention or Treatment.” The purpose of this guidance is to assist sponsors in the clinical development of drugs, biological products, and certain devices for the prevention or treatment of aGVHD or cGVHD. Specifically, this guidance addresses FDA's current thinking regarding the overall clinical development program and critical design elements for early and late phase trials for the intended populations.

                    aGVHD and cGVHD are clinical syndromes that may arise after allogeneic hematopoietic stem cell transplantation as a result of                           ( print page 67303)                        immunocompetent donor cells recognizing and reacting to disparity with major or minor histocompatibility antigens on recipient tissues. The classical approach to prevention of GVHD involves pharmacological or physical methods to delete alloreactive T cells in the immediate peritransplant setting with or without additional drugs to prevent activation of naive T cells. Should aGVHD or cGVHD occur despite these measures, treatment has depended largely on drugs that impair T cells. Further basic science investigations have elucidated the molecular mechanisms behind the clinical manifestations of aGVHD and cGVHD, including cytokines, the innate immune system, and components of the adaptive immune system other than T cells. These scientific advances have provided opportunities for development of biomarkers to identify the specific immune dysfunction present in an individual patient and for development of drugs to modulate the immune system with precision rather than to just suppress the immune system globally.                

Given the complexity of the clinical manifestation of aGVHD and cGVHD and the potential for a paradigm shift in the management of GVHD, this guidance provides recommendations regarding the design and conduct of clinical trials and the types of supporting data that could facilitate efficient development of drugs and/or certain devices for the prevention or treatment of aGVHD or cGVHD. This guidance also provides recommendations on what should be included in the marketing application to facilitate review.

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 “Graft-versus-Host Diseases: Developing Drugs, Biological Products, and Certain Devices for Prevention or Treatment.” 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 part 314 have been approved under OMB control number 0910-0001; 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 812 have been approved under OMB control number 0910-0078; and the collections of information in 21 CFR parts 50 and 56 have been approved under OMB control number 0910-0130.

## III. Electronic Access

                    Persons with access to the internet may obtain the draft guidance at                     *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: September 26, 2023.

Lauren K. Roth,

Associate Commissioner for Policy.

[FR Doc. 2023-21524 Filed 9-28-23; 8:45 am]

BILLING CODE 4164-01-P