Notice2023-28210
Master Protocols for Drug and Biological Product Development; Draft Guidance for Industry; Availability
Primary source
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Published
December 22, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Master Protocols for Drug and Biological Product Development." The draft guidance addresses the design and analysis of trials conducted under a master protocol as well as the submission of documentation to support regulatory review. The primary focus is on randomized umbrella and platform trials that are intended to contribute to a demonstration of safety and substantial evidence of effectiveness. The considerations in this guidance apply to a range of therapeutic areas. The draft guidance is intended to clarify the Agency's thinking on the use of master protocols in drug and biological product development, which was previously addressed in FDA's guidance entitled "COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention." FDA is also announcing the withdrawal of the guidance entitled "COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention."
Full Text
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<title>Federal Register, Volume 88 Issue 245 (Friday, December 22, 2023)</title>
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[Federal Register Volume 88, Number 245 (Friday, December 22, 2023)]
[Notices]
[Pages 88623-88625]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-28210]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-D-5259]
Master Protocols for Drug and Biological Product Development;
Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Master
Protocols for Drug and Biological Product Development.'' The draft
guidance addresses the design and analysis of trials conducted under a
master protocol as well as the submission of documentation to support
regulatory review. The primary focus is on randomized umbrella and
platform trials that are intended to contribute to a demonstration of
safety and substantial evidence of effectiveness. The considerations in
this guidance apply to a range of therapeutic areas. The draft guidance
is intended to clarify the Agency's thinking on the use of master
protocols in drug and biological product development, which was
previously addressed in FDA's guidance entitled ``COVID-19: Master
Protocols Evaluating Drugs and Biological
[[Page 88624]]
Products for Treatment or Prevention.'' FDA is also announcing the
withdrawal of the guidance entitled ``COVID-19: Master Protocols
Evaluating Drugs and Biological Products for Treatment or Prevention.''
DATES: Submit either electronic or written comments on the draft
guidance by February 20, 2024 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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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-5259 for ``Master Protocols for Drug and Biological Product
Development.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 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 draft guidance document.
FOR FURTHER INFORMATION CONTACT: Scott N. Goldie, Center for Drug
Evaluation and Research, Office of Biostatistics, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 3557, Silver
Spring, MD 20993-0002, 301-796-2055; or Anne Taylor, 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 draft guidance for industry
entitled ``Master Protocols for Drug and Biological Product
Development.'' The draft guidance addresses the design and analysis of
trials conducted under a master protocol as well as the submission of
documentation to support regulatory review. The primary focus of this
guidance is on randomized umbrella and platform trials that are
intended to contribute to a demonstration of safety and substantial
evidence of effectiveness. The concepts discussed may also be useful to
consider for early-phase or exploratory umbrella and platform trials as
well as those conducted to satisfy post-marketing commitments or
requirements. The considerations in this draft guidance apply to a
range of therapeutic areas.
Well-designed and -conducted trials using master protocols can
accelerate drug development by maximizing the amount of information
obtained from the research effort. Compared with stand-alone trials
under separate protocols, a master protocol may offer certain
advantages by leveraging a shared control arm and other shared protocol
elements (e.g., visit schedule, measurement procedures), shared
infrastructure (e.g., network of clinical sites, central facilities,
central randomization system, data management systems), and shared
oversight (e.g., steering committee, data review committee). At the
same time, master protocols add elements of complexity, which can
increase startup time and can lead to design challenges such as
ensuring adequate blinding to treatment assignment. Additionally,
master protocols involving multiple stakeholders will require a high
degree of coordination.
[[Page 88625]]
FDA provided recommendations on master protocols for COVID-19 drug
and biological products in the guidance entitled ``COVID-19: Master
Protocols Evaluating Drugs and Biological Products for Treatment or
Prevention,'' which posted May 2021 and was announced in the Federal
Register on June 24, 2021 (86 FR 33309) (hereafter ``2021 COVID-19
Master Protocols Guidance''). FDA issued the guidance to communicate
its policy for the duration of the COVID-19 public health emergency
(PHE) declared by the Secretary of Health and Human Services (HHS) on
January 31, 2020, including any renewals made by the HHS Secretary in
accordance with section 319(a)(2) of the Public Health Service Act (42
U.S.C. 247d(a)(2)). Furthermore, in the Federal Register of March 13,
2023 (88 FR 15417), FDA listed the guidance documents that will no
longer be effective with the expiration of the PHE declaration,
guidances that FDA was revising to continue in effect for 180 days
after the expiration of the PHE declaration to provide a period for
stakeholder transition and then would no longer be in effect, and
guidances that FDA was revising to continue in effect for 180 days
after the expiration of the PHE declaration during which time FDA
planned to further revise the guidances. The 2021 COVID-19 Master
Protocols Guidance is included in the latter category. The 2021 COVID-
19 Master Protocols Guidance was revised to remain in effect for 180
days post expiration of the PHE declaration, and then revised again to
remain in effect until March 7, 2024, so that FDA could further revise
the 2021 guidance.
FDA is issuing this draft guidance because many of the issues
addressed in the 2021 guidance arise outside the context of the COVID-
19 PHE. The recommendations in this draft guidance apply to a range of
therapeutic areas, not just COVID-19. The draft guidance also provides
a more comprehensive discussion of many of the design and analysis
topics covered in the 2021 COVID-19 Master Protocols Guidance. For
example, the draft guidance provides more detailed considerations
related to randomization, the choice of control group, informed
consent, blinding to treatment assignment, adaptive design,
multiplicity, comparisons between drugs, and the evaluation of drug
safety. The draft guidance also expands on considerations for trial
oversight, data sharing, dissemination of information, and submissions
to support regulatory review. The draft guidance, when finalized, will
represent the Agency's current thinking on the use of master protocols
in drug and biological product development.
FDA is issuing this guidance to satisfy, in part, a mandate under
section 3607(b)(2)(C-F) of the Food and Drug Omnibus Reform Act of 2022
(FDORA). Consistent with the FDORA mandate, this guidance discusses
recommendations for clinical trials to streamline logistics and
facilitate the efficient collection and analysis of data, as well as
important principles for the evaluation of effectiveness,
recommendations for communication between sponsors and FDA, and
considerations related to ensuring participant safety and data
integrity in such trials.
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 ``Master
Protocols for Drug and Biological Product Development.'' 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.
FDA is also announcing that the 2021 COVID-19 Master Protocols
Guidance will be withdrawn upon publication of this draft guidance. FDA
has determined that the 2021 COVID-19 Master Protocols Guidance is no
longer needed because this new draft is available and its
recommendations, when finalized, will be applicable outside the context
of the COVID-19 PHE.
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 312 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. The information collections for new drug application (NDA)
regulations (including abbreviated new drug applications (ANDAs)) (21
CFR part 314) and related guidances are approved under OMB control
number 0910-0001, and our biological licensing applications (BLA)
regulations (21 CFR part 601) are approved under OMB control number
0910-0338. The collections of information in 21 CFR parts 50 and 56 for
the protection of human subjects and institutional review boards have
been approved under OMB control number 0910-0130. The collections of
information related to the protection of human subjects under 45 CFR
part 46 and to IRB recordkeeping under 45 CFR 46.115 have been approved
under OMB control number 0990-0260. The collections of information in
21 CFR part 11, Electronic Records; Electronic Signatures, have been
approved under OMB control number 0910-0303. The information collection
requirements 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. The information collection
requirements in FDA's guidance for industry entitled ``Oversight of
Clinical Investigations--A Risk-Based Approach to Monitoring'' and
FDA's final guidance for industry entitled ``A Risk-Based Approach to
Monitoring of Clinical Investigations'' have been approved under OMB
control number 0910-0733. The information 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.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: December 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-28210 Filed 12-21-23; 8:45 am]
BILLING CODE 4164-01-P
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