Master Protocols for Drug and Biological Product Development; Draft Guidance for Industry; Availability, 88623-88625 [2023-28210]
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Federal Register / Vol. 88, No. 245 / Friday, December 22, 2023 / Notices
ddrumheller on DSK120RN23PROD with NOTICES1
1320.3(c) and includes agency requests
or requirements that members of the
public submit reports, keep records, or
provide information to a third party.
Section 3506(c)(2)(A) of the PRA
requires Federal agencies to publish a
60-day notice in the Federal Register
concerning each proposed collection of
information, including each proposed
extension or reinstatement of an existing
collection of information, before
submitting the collection to OMB for
approval. To comply with this
requirement, CMS is publishing this
notice.
Information Collection
1. Type of Information Collection
Request: New collection; Title of
Information Collection: American
Dental Association (ADA) Dental Claim
Form; Use: Medicare has traditionally
accepted the Professional (CMS–1500/
837P transaction) and Institutional
(UB04/837I transaction) claims forms to
provide payment for Medicare-covered
services. The Centers for Medicare &
Medicaid Services (CMS) now plans to
allow providers to submit Medicarecovered dental services on the dental
claim form, a similar information
collection as the already-approved
professional and institutional claim
forms. The ADA Dental Claim Form will
be used to deliver information from
dental providers to CMS for CMS to
reimburse for provided dental services.
Medicare Part B MACs will use the data
collected on the ADA dental form to
determine the proper amount of
reimbursement for Part B dental services
provided to Medicare beneficiaries.
Submission of information on the ADA
Dental Claim Form and associated
HIPAA-standard 837D transaction
format permits Medicare Part B MACs to
receive consistent data for proper
benefit payment. Form Number: CMS–
10883 (OMB control number: 0938New); Frequency: Occasionally;
Affected Public: Private sector,
Businesses and other for-profits;
Number of Respondents: 50,000; Total
Annual Responses: 50,000; Total
Annual Hours: 12,500. (For policy
questions regarding this collection
contact Charlene Parks at 410–786–
8684.)
2. Type of Information Collection
Request: Reinstatement without change
of a previously approved collection;
Title of Information Collection: Indirect
Medical Education and Direct Graduate
Medical Education; Use: Section
1886(d)(5)(B) of the Social Security Act
requires additional payments to be
made under the Medicare Prospective
Payment System (PPS) for the indirect
medical educational costs a hospital
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incurs in connection with interns and
residents (IRs) in approved teaching
programs. In addition, title 42, part 413,
sections 75 through 83 implement
section 1886(d) of the Act by
establishing the methodology for
Medicare payment for the costs of direct
graduate medical educational activities.
The information collected on IRs is
used by Part-A Medicare Administrative
Contractors (MAC) to verify the number
of IRs FTE used in the calculation of
Medicare payments for IME and GME.
The IR data submitted by the hospitals
to the MACs is uploaded into CMS’
Intern and Resident Information System
(IRIS) database to identify duplicate
FTEs reported for any IR.
The MACs use the information
collected on IRs to ensure that all
program payments for IME and GME are
accurate and are in accordance with
Medicare regulations. The IR data
submitted by the hospitals to the MACs
are used to audit the Medicare cost
reports filed by the hospitals. Form
Number: CMS–R–64 (OMB control
number: 0938–0456); Frequency:
Monthly; Affected Public: Private sector
and Federal Government; Number of
Respondents: 1,245; Total Annual
Responses: 1,245; Total Annual Hours:
2,490. (For policy questions regarding
this collection contact Owen Osaghae at
410–786–7550.)
3. Type of Information Collection
Request: Extension without change of a
currently approved collection; Title of
Information Collection: Medication
Therapy Management Program
Improvements—Standardized Format;
Use: Section 1860D–4(c)(2)(C)(i) of the
Act requires plan sponsors to offer MTM
services that include an annual CMR
with a written summary and action plan
provided in a standardized format
developed in consultation with
stakeholders. This requirement is
codified at § 423.153(d)(1)(vii)(D),
which requires that the standardized
action plan and summary comply with
requirements specified by CMS for the
standardized format. Components of the
CMR summary in Standardized Format
should include a cover letter,
personalized medication list, and action
plan if applicable.
Users include members in a Part D
sponsors’ plan who are eligible are
enrolled in the sponsors’ MTM program
and offered a CMR. The CMR is a
consultation between the MTM provider
(such as a pharmacist) with the
beneficiary to review their medications.
The MTM provider is either an
employee/contractor of the plan itself or
of a downstream entity contracted by
the plan to provide MTM services. After
a CMR is performed, the sponsor creates
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88623
and sends a summary of the CMR to the
beneficiary that includes a medication
action plan and personal medication list
using the Standardized Format.
Information collected by Part D MTM
programs as required by the
Standardized Format for the CMR
summary is used by beneficiaries or
their authorized representatives,
caregivers, and their healthcare
providers to improve medication use
and achieve better healthcare outcomes.
Form Number: CMS–10396 (OMB
control number: 0938–1154); Frequency:
Yearly; Affected Public: Private Sector
and Business or other for-profits;
Number of Respondents: 842; Total
Annual Responses: 2,382,774; Total
Annual Hours: 1,588,595. (For policy
questions regarding this collection
contact Victoria Dang at 410–786–3991
or Victoria.dang@cms.hhs.gov.)
Dated: December 19, 2023.
William N. Parham, III,
Director, Paperwork Reduction Staff, Office
of Strategic Operations and Regulatory
Affairs.
[FR Doc. 2023–28292 Filed 12–21–23; 8:45 am]
BILLING CODE 4120–01–P
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.
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
SUMMARY:
E:\FR\FM\22DEN1.SGM
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Federal Register / Vol. 88, No. 245 / Friday, December 22, 2023 / Notices
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.’’
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:
DATES:
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’’).
ddrumheller on DSK120RN23PROD with NOTICES1
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–5259 for ‘‘Master Protocols for
Drug and Biological Product
Development.’’ Received comments will
be placed in the docket and, except for
VerDate Sep<11>2014
18:10 Dec 21, 2023
Jkt 262001
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-201509-18/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 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–
PO 00000
Frm 00066
Fmt 4703
Sfmt 4703
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.
E:\FR\FM\22DEN1.SGM
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ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 88, No. 245 / Friday, December 22, 2023 / Notices
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
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18:10 Dec 21, 2023
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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
PO 00000
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88625
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 https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, https://
www.fda.gov/regulatory-information/
search-fda-guidance-documents, or
https://www.regulations.gov.
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2019–E–3017]
Determination of Regulatory Review
Period for Purposes of Patent
Extension; Emgality
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
E:\FR\FM\22DEN1.SGM
Notice.
22DEN1
Agencies
[Federal Register Volume 88, Number 245 (Friday, December 22, 2023)]
[Notices]
[Pages 88623-88625]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-28210]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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:
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-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 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 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 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: December 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-28210 Filed 12-21-23; 8:45 am]
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