[Federal Register Volume 88, Number 188 (Friday, September 29, 2023)]
[Notices]
[Pages 67301-67303]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-21524]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Graft-Versus-Host Diseases: Developing Drugs, Biological 
Products, and Certain Devices for Prevention or Treatment; Draft 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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[[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the availability of a draft guidance for industry entitled ``Graft-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DATES: Submit either electronic or written comments on the draft 
guidance by November 28, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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.
    <bullet> 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

[[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