[Federal Register Volume 87, Number 233 (Tuesday, December 6, 2022)]
[Notices]
[Pages 74635-74637]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-26464]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-0691]


Pharmacokinetic-Based Criteria for Supporting Alternative Dosing 
Regimens of Programmed Cell Death Receptor-1 or Programmed Cell Death-
Ligand 1 Blocking Antibodies for Treatment of Patients With Cancer; 
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 final guidance for industry entitled 
``Pharmacokinetic-Based Criteria for Supporting Alternative Dosing 
Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell 
Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients 
with Cancer.'' This guidance provides recommendations for sponsors of 
investigational new drug applications (INDs) and biologics license 
applications (BLAs) on the use of pharmacokinetic (PK)-based criteria 
to support the approval of alternative dosing regimens for programmed 
cell death receptor-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) 
blocking antibodies. This guidance is based on accumulated scientific 
and regulatory experience for PD-1 and PD-L1 drugs, and as such, does 
not address development of alternative dosing regimens for other drugs 
or biologics, changes in route of administration, or novel formulations 
of previously approved PD-1/PD-L1 products. This guidance finalizes the 
draft guidance of the same title issued on August 26, 2021.

DATES: The announcement of the guidance is published in the Federal 
Register on December 6, 2022.

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

[[Page 74636]]

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-0691 for ``Pharmacokinetic-Based Criteria for Supporting 
Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) 
or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for 
Treatment of Patients with Cancer.'' 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 this 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. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Brian Booth, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Avenue, Building 51, Silver Spring, MD 20993, 301-796-1508.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Pharmacokinetic-Based Criteria for Supporting Alternative 
Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or 
Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for 
Treatment of Patients with Cancer.'' This guidance provides 
recommendations for sponsors of INDs and BLAs on the use of PK-based 
criteria to support the approval of alternative dosing regimens for PD-
1 or PD-L1 blocking antibodies. The guidance is based on accumulated 
scientific and regulatory experience for PD-1 and PD-L1 drugs, as such, 
does not address development of alternative dosing regimens for any 
other drugs or biologics, changes in route of administration, or novel 
formulations of previously approved PD-1/PD-L1 products.
    Sponsors may seek approval of alternative intravenous (IV) dosing 
regimens that are different from those tested in the original clinical 
efficacy and safety trials that served as the basis of approval of the 
current dosing regimen, or in the pre-approval setting, dosing regimens 
that differ from those tested in earlier PK and efficacy studies 
conducted during development. These alternative IV dosing regimens are 
typically designed to change doses and dosing intervals. Longer dosing 
intervals can minimize patient burden and reduce risks associated with 
more frequent administration (e.g., infusion reactions), as well as 
exposure to communicable diseases (e.g., SARS-CoV-2) associated with 
visits to hospitals or infusion centers. The guidance describes the 
criteria for using the PK-based approach and the documents that should 
be included in the submissions seeking approval.
    This guidance finalizes the draft guidance of the same title issued 
on August 26, 2021 (86 FR 47649). FDA considered comments received on 
the draft guidance as it finalized the guidance. Changes from the draft 
to the final guidance include: (1) PK-based approach to support 
approval of alternative dosing regimens for PD-1/PD-L1 blocking 
antibody products may apply to pre- and post-approval setting and (2) 
this approach may apply to PD-1/PD-L1 monotherapies and combination 
regimens where the dose and/or dose schedule of the PD-1/PD-L1 is the 
only proposed change. In addition, editorial changes were made to 
improve clarity.
    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 ``Pharmacokinetic-Based Criteria for 
Supporting Alternative Dosing Regimens of Programmed Cell Death 
Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking 
Antibodies for Treatment of Patients with Cancer.'' It does not 
establish any rights for any person and is not binding on FDA or the 
public. You can use another 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. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of

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information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 312 have been approved under OMB control 
number 0910-0014; and the collections of information in 21 CFR part 601 
have been approved under OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: November 30, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-26464 Filed 12-5-22; 8:45 am]
BILLING CODE 4164-01-P


