[Federal Register Volume 88, Number 58 (Monday, March 27, 2023)]
[Notices]
[Pages 18148-18149]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-05910]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-0110]


Clinical Trial Considerations To Support Accelerated Approval of 
Oncology Therapeutics; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Clinical 
Trial Considerations to Support Accelerated Approval of Oncology 
Therapeutics.'' The purpose of this guidance is to provide 
recommendations to sponsors of anti-cancer drugs or biological products 
on considerations for designing trials intended to support accelerated 
approval. The accelerated approval pathway is commonly used for 
approval of oncology drugs due to the serious and life-threatening 
nature of cancer. Although single-arm trials have been commonly used to 
support accelerated approval, a randomized controlled trial is the 
preferred approach as it provides a more robust efficacy and safety 
assessment and allows for direct comparisons to an available therapy. 
This guidance describes considerations for designing, conducting, and 
analyzing data for trials intended to support accelerated approvals of 
oncology therapeutics.

DATES: Submit either electronic or written comments on the draft 
guidance by May 26, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-0110 for ``Clinical Trial Considerations to Support 
Accelerated Approval of Oncology Therapeutics.'' 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

[[Page 18149]]

and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 
4th Floor, Silver Spring, MD 20993-0002; or to the 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: Lola Fashoyin-Aje, Oncology Center of 
Excellence, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2352, Silver 
Spring, MD 20993, 240-402-0205; or Diane Maloney, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7242, Silver Spring, MD 20993, 240-402-
8113.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Clinical Trial Considerations to Support Accelerated 
Approval of Oncology Therapeutics.'' The purpose of this guidance is to 
provide recommendations to sponsors of anti-cancer drugs or biological 
products on considerations for designing trials intended to support 
accelerated approval. The accelerated approval pathway is commonly used 
for approval of oncology drugs in part due to the serious and life-
threatening nature of cancer and because of available surrogate or 
intermediate clinical endpoints considered reasonably likely to predict 
clinical benefit. Single-arm trial designs and response rate endpoints 
(with duration of response as supportive) have most commonly been used 
in oncology because response rate is a marker of drug activity since 
malignant tumors do not typically regress on their own, and response 
rate can be interpreted in single-arm trials for monotherapy drug 
regimens. However, there are limitations to the use of single-arm 
trials in support of accelerated approval, including but not limited 
to: small safety datasets, low magnitude response rates that may not be 
reasonably likely to predict clinical benefit, and the inability to 
establish differential contribution of effect for combination regimens. 
Additionally, the reliance on cross-trial comparisons to historical 
trials to assess whether the observed treatment effect represents an 
improvement over available therapy is challenging. These limitations 
add uncertainty to the assessment of the safety and/or effectiveness of 
a drug such that accelerated approval based on a single-arm trial may 
not be justified in a given clinical setting.
    Given the limitations of single-arm trials, FDA considers a 
randomized controlled trial to be the most appropriate trial design to 
support accelerated approval of oncology drugs. When properly designed 
and executed, a randomized controlled trial provides a more robust 
efficacy and safety assessment and allows for direct comparisons to a 
concurrent control arm. Sponsors can, as appropriate, elect to conduct 
a single randomized controlled trial to support an accelerated approval 
and to verify clinical benefit (i.e., follow the ``one-trial'' 
approach), or they can conduct separate trials--one to support the 
accelerated approval and another, a confirmatory trial, to verify 
clinical benefit. The ``one-trial'' approach maintains efficiency in 
drug development by providing early access to an investigational drug 
using the accelerated approval pathway, while ensuring that a 
postmarketing trial is fully accrued and well underway to verify longer 
term benefit in a timely fashion.
    This guidance describes considerations for designing, conducting, 
and analyzing data for trials intended to support accelerated approval 
of oncology drugs. Specifically, the guidance provides recommendations 
addressing the design, conduct, and analyses of data for either two 
separate randomized controlled trials or for using the ``one-trial'' 
approach for accelerated approval. The guidance also provides 
recommendations for designing, conducting, and analyzing data from a 
single-arm trial intended to support accelerated approval (when 
appropriate), and the considerations for determining whether the data 
may be adequate for this purpose. Regardless of the approach under 
consideration, FDA recommends early discussion before study initiation 
and during trials, as appropriate.
    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 ``Clinical 
Trial Considerations to Support Accelerated Approval of Oncology 
Therapeutics.'' 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 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; 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/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: March 17, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-05910 Filed 3-24-23; 8:45 am]
BILLING CODE 4164-01-P


