[Federal Register Volume 88, Number 11 (Wednesday, January 18, 2023)]
[Notices]
[Pages 2932-2933]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-00837]


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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Products for the Treatment of Oncologic Diseases; Draft Guidance for 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the availability of a draft guidance for industry entitled ``Optimizing 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 the optimal 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 nor does it 
address dosage optimization for radiopharmaceuticals, cellular and gene 
therapy products, microbiota, or cancer vaccines.

DATES: Submit either electronic or written comments on the draft 
guidance by March 20, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-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 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; 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 draft 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 Stephen 
Ripley, Center of Biologics Evaluation

[[Page 2933]]

and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 71, Rm, 7301, Silver Spring, MD 20993, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft 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 chemotherapy drugs based on their observed 
steep dose-response, their limited drug target specificity, and the 
willingness of patients and providers to accept substantial toxicity to 
treat a serious, life-threatening disease. Most modern oncology drugs, 
such as kinase inhibitors and monoclonal antibodies, are designed to 
interact with a molecular pathway unique to an oncologic disease(s) 
(i.e., targeted therapies). These targeted therapies demonstrate 
different dose-response relationships compared to cytotoxic 
chemotherapy, such that doses below the MTD may have similar efficacy 
to the MTD but with fewer toxicities.
    This draft guidance is intended to assist sponsors in identifying 
the optimal 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 and does not address selection of the starting 
dosage for first-in-human trials nor does it address dosage 
optimization for radiopharmaceuticals, cellular and gene therapy 
products, microbiota, or cancer vaccines. This guidance should be 
considered along with the International Conference on Harmonisation 
(ICH) E4 guidance entitled ``Dose-Response Information to Support Drug 
Registration'' when identifying the optimal dosage(s).
    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 ``Optimizing 
the Dosage of Human Prescription Drugs and Biological Products for the 
Treatment of Oncologic Diseases.'' 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. 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 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR parts 50 and 56 have been approved under OMB 
control number 0910-0130; 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/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: January 12, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-00837 Filed 1-17-23; 8:45 am]
BILLING CODE 4164-01-P


