Document ID: FDA-2018-D-3292-0020
Agency: fda
Document Type: Notice
Title: Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics; Guidance for Industry; Availability
Posted Date: 2022-03-02T05:00Z

[Federal Register Volume 87, Number 41 (Wednesday, March 2, 2022)]
[Notices]
[Pages 11722-11724]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-04398]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3292]

Master Protocols: Efficient Clinical Trial Design Strategies To 
Expedite Development of Oncology Drugs and Biologics; 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 ``Master 
Protocols: Efficient Clinical Trial Design Strategies to Expedite 
Development of Oncology Drugs and Biologics.'' This guidance provides 
advice to sponsors of drugs and biologics for cancer treatment 
regarding the design and conduct of clinical trials, other than first-
in-human trials, intended to simultaneously evaluate more than one 
investigational drug and/or more than one cancer type within the same 
overall trial structure (master protocols) in adult and pediatric 
cancers. In contrast to traditional trial designs, where a single drug 
is tested in a single disease population in one clinical trial, master 
protocols use a single infrastructure, trial design, and protocol to 
simultaneously evaluate multiple drugs and/or disease populations in 
multiple substudies, allowing for efficient and accelerated drug 
development.

DATES: The announcement of the guidance is published in the Federal 
Register on March 2, 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 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-2018-D-3292 for ``Master Protocols: Efficient Clinical Trial Design 
Strategies to Expedite Development of Oncology Drugs and Biologics.'' 
Received comments will be placed in the docket

[[Page 11723]]

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 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. 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: Lee Pai-Scherf, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2314, Silver Spring, MD 20993, 301-796-
3400; or Stephen Ripley, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 
7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a final guidance for industry 
entitled ``Master Protocols: Efficient Clinical Trial Design Strategies 
to Expedite Development of Oncology Drugs and Biologics.''
    This guidance provides recommendations to sponsors of drugs or 
biologics for the treatment of cancer regarding the design and conduct 
of clinical trials intended to simultaneously evaluate more than one 
investigational drug and/or more than one cancer type within the same 
overall trial structure (master protocols) in adult and pediatric 
cancers. In general, the recommended phase 2 dose should have been 
established for an investigational drug or drugs evaluated in a master 
protocol. It also describes aspects of master protocol designs and 
trial conduct and related considerations, such as biomarker 
codevelopment and statistical analysis considerations, and provides 
advice on the information that sponsors should submit to FDA and on how 
sponsors can interact with FDA to facilitate efficient review.
    This guidance does not address all issues relating to clinical 
trial design, statistical analysis, or the biomarker development 
process. Those topics are addressed in the International Council for 
Harmonisation (ICH) guidances for industry ``E9 Statistical Principles 
for Clinical Trials'' and ``E10 Choice of Control Group and Related 
Issues in Clinical Trials'' and the guidance for industry and FDA staff 
``In Vitro Companion Diagnostic Devices.''
    This guidance finalizes the draft guidance of the same name issued 
on October 1, 2018 (83 FR 49398). FDA considered comments received on 
the draft guidance as the guidance was finalized. Changes from the 
draft to the final guidance include adding information about a dose-
finding or safety lead-in component in basket trials when evaluating an 
investigational drug combination and comparison between experimental 
arms in umbrella trials and acceptable statistical approaches. 
Revisions were also made to various sections of the draft guidance to 
clarify the information to be submitted to FDA to support amendments to 
expand the protocol, the frequency of cumulative safety updates, the 
role of ad hoc institutional review board meetings, the role of the 
safety assessment committee, and informed consent requirements.
    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 ``Master Protocols: Efficient Clinical Trial 
Design Strategies to Expedite Development of Oncology Drugs and 
Biologics.'' 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 314.50(d)(5) (clinical data section) and 
(d)(6) (statistical section) have been approved under OMB control 
number 0910-0001; the collections of information in 21 CFR part 312, 
subpart B, for the submission of investigational new drug applications 
(INDs), including protocols, protocol amendments, and information 
amendments, have been approved under OMB control number 0910-0014. 
Sponsors may request comment and advice on an IND as well as request 
meetings with FDA under 21 CFR part 312, subpart C (OMB control number 
0910-0014).
    The collections of information in 21 CFR part 11 have been approved 
under OMB control number 0910-0303; the collections of information in 
parts 50 and 56 for the protection of human subjects and institutional 
review boards have been approved under OMB control numbers 0910-0130; 
Responsibilities of sponsors and investigators (21 CFR part 312, 
subpart D) are also covered under OMB control number 0910-0014; the 
collections of information in 21 CFR part 601 have been approved under

[[Page 11724]]

OMB control number 0910-0338; the collections of information in 
Sec. Sec.  201.56 and 201.57 for the content and format requirements 
for labeling of human prescription drug and biological products have 
been approved under OMB control number 0910-0572.
    In addition, the following collections of information in FDA's 
guidances have been approved by OMB (https://www.fda.gov/regulatory-information/search-fda-guidance-documents):
     Collections in FDA's draft guidance for industry entitled 
``Formal Meetings Between the FDA and Sponsors and Applicants for PDUFA 
Products'' have been approved under OMB control number 0910-0429.
     Collections in FDA's guidance for industry entitled 
``Special Protocol Assessment'' have been approved under OMB control 
number 0910-0470.
     Collections in FDA's guidance for industry entitled 
``Establishment and Operation of Clinical Trial Data Monitoring 
Committees'' have been approved under OMB control number 0910-0581.
     Collections in FDA's guidance for industry entitled 
``Oversight of Clinical Investigations--A Risk-Based Approach to 
Monitoring'' have been approved under OMB control number 0910-0733.
     Collections in FDA's guidance for industry entitled 
``Expedited Programs for Serious Conditions--Drugs and Biologics'' have 
been approved under OMB control number 0910-0765.
     Collections in FDA's guidance for industry entitled 
``E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1)'' 
have been approved under OMB control number 0910-0843.

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, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: February 24, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-04398 Filed 3-1-22; 8:45 am]
BILLING CODE 4164-01-P