[Federal Register Volume 89, Number 154 (Friday, August 9, 2024)]
[Notices]
[Pages 65366-65368]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-17771]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-2827]


Optimizing the Dosage of Human Prescription Drugs and Biological 
Products for the Treatment of Oncologic Diseases; 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 ``Optimizing 
the Dosage of Human Prescription Drugs and Biological Products for the 
Treatment of Oncologic Diseases.'' This guidance is intended to assist 
sponsors in identifying an optimized dosage(s) for human prescription 
drugs or biological products for the treatment of oncologic diseases 
during clinical development prior to submitting an application for 
approval for a new indication and usage. This guidance does not address 
selection of the starting dosage for first-in-human trials. In 
addition, this guidance does not address dosage optimization for 
radiopharmaceuticals, cellular and gene therapy products, oncolytics, 
microbiota, or cancer vaccines, nor does it specifically address 
pediatric drug development. However, some of the principles outlined 
may be applicable to these therapeutic modalities or to dosage 
optimization for pediatric patients. This guidance finalizes the draft 
guidance of the same title ``Optimizing the Dosage of Human 
Prescription Drugs and Biological Products for the Treatment of 
Oncologic Diseases'' issued on January 23, 2023.

DATES: The announcement of the guidance is published in the Federal 
Register on August 9, 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

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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-2022-D-2827 for ``Optimizing the Dosage of Human Prescription Drugs 
and Biological Products for the Treatment of Oncologic Diseases.'' 
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 or Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, 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 that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Mirat Shah, Center for Drug Evaluation 
and Research (HFD-150), Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-8547; or James 
Myers, Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver 
Spring, MD 20993, 240-402-7910.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Optimizing the Dosage of Human Prescription Drugs and 
Biological Products for the Treatment of Oncologic Diseases.'' Dose-
finding trials (i.e., trials that include dose-escalation and dose-
expansion portions with the primary objective of selecting the 
recommended phase II dose) for oncology drugs have historically been 
designed to determine the maximum tolerated dose (MTD). This paradigm 
was developed for cytotoxic chemotherapies based on their observed 
steep dose-response relationships, their limited drug target 
specificity, and the willingness of patients and providers to accept 
substantial toxicity due to the lack of effective alternatives for this 
serious, life-threatening disease. Most modern oncology drugs, such as 
kinase inhibitors and antibodies, are designed to interact with a 
molecular pathway critical to an oncologic disease(s) (i.e., targeted 
therapies). These drugs demonstrate different dose-response 
relationships compared to cytotoxic chemotherapy, such that doses below 
the MTD may have similar activity to the MTD but with fewer toxicities 
or the MTD may never be reached.
    This guidance finalizes the draft guidance entitled ``Optimizing 
the Dosage of Human Prescription Drugs and Biological Products for the 
Treatment of Oncologic Disease'' issued on January 23, 2023 (88 FR 
2932). FDA considered comments received on the draft guidance as the 
guidance was finalized. Changes from the draft to the final guidance 
include emphasis on FDA's availability to provide product-specific 
advice since there is not a one size fits all approach and clarity on 
the collection and analysis of key pharmacologic data. 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 ``Optimizing the Dosage of Human 
Prescription Drugs and Biological Products for the Treatment of 
Oncologic Disease.'' 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 (PRA) (44 U.S.C. 3501-3521). 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 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 draft guidance 
at https://www.fda.gov/drugs/guidance-compliance-regulatory-
information/

[[Page 65368]]

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: August 6, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-17771 Filed 8-8-24; 8:45 am]
BILLING CODE 4164-01-P