83 FR 49398 - Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 190 (October 1, 2018)

Page Range		49398-49400
FR Document		2018-21313

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics.''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 (FIH) 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.

Federal Register, Volume 83 Issue 190 (Monday, October 1, 2018)

[Federal Register Volume 83, Number 190 (Monday, October 1, 2018)]
[Notices]
[Pages 49398-49400]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2018-21313]


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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Expedite Development of Oncology Drugs and Biologics; Draft Guidance 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the availability of a draft guidance for industry entitled ``Master 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: 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 (FIH) 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: Submit either electronic or written comments on the draft 
guidance by November 30, 2018 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-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 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.
     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.thefederalregister.org/fdsys/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.
    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, 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: Lee Pai-Scherf, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire

[[Page 49399]]

Ave., Bldg. 22, Rm. 2314, Silver Spring, MD 20993-0002, 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 draft 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 
treatment of cancer regarding the design and conduct of clinical 
trials, other than FIH 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.
    There is increased interest in expediting late-stage drug 
development through developing trial designs that test multiple drugs 
and/or multiple cancer subpopulations in parallel under a single 
protocol, without a need to develop new protocols for every trial. The 
term master protocol is often used to describe the design of such 
trials, with variable terms such as umbrella, basket, or platform 
describing specific designs. Examples of trials using master protocols 
include the Lung-MAP trial (NCT02154490), the NCI-MATCH trial (EAY131, 
NCT02465060), and the Pediatric MATCH trial (APEC1621, NCT03155620). 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.
    Because of the complexity of these trials evaluating multiple drugs 
and/or disease populations and the potential regulatory impact, it is 
important that such trials be well designed and well conducted to 
ensure patient safety and to obtain quality data that may support drug 
approval.
    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: 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. This guidance is not subject to 
Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act (PRA) of 1995 (44 U.S.C. 3501-3520).
    FDA has OMB approval under the PRA (control number 0910-0014) for 
the submission of investigational new drug applications (INDs), 
including protocols, protocol amendments, and information amendments, 
in 21 CFR part 312, subpart B. 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). Responsibilities of sponsors 
and investigators (21 CFR part 312, subpart D) is also covered under 
OMB control number 0910-0014.
    In addition, the following collections of information that have 
been approved by OMB would cover other submissions discussed in the 
draft guidance:
     Collections of information referred to in the guidance for 
industry entitled ``Special Protocol Assessment'' (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm498793.pdf) have been approved under OMB control number 
0910-0470;
     Collections of information referred to in the guidance for 
industry entitled ``Establishment and Operation of Clinical Trial Data 
Monitoring Committees'' (available at https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm127073.pdf) have been approved under 
OMB control number 0910-0581;
     Collections of information referred to in the guidance for 
industry entitled ``Oversight of Clinical Investigations--A Risk-Based 
Approach to Monitoring (available at https://www.fda.gov/downloads/Drugs/Guidances/UCM269919.pdf) has been approved under OMB control 
number 0910-0733;
     Collections of information referred to in the ICH guidance 
for industry entitled ``E6(R2) Good Clinical Practice: Integrated 
Addendum to E6(R1) (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm464506.pdf) has been 
approved under OMB control number 0910-0843.
     Collections of information in 21 CFR parts 50 and 56 have 
been approved under OMB control number 0910-0755;
     Collections of information under 21 CFR 56.115 have been 
approved under OMB control number 0910-0130;
     Collections of information referred to in the guidance for 
industry entitled ``Expedited Programs for Serious Conditions--Drugs 
and Biologics,'' (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm358301.pdf) including 
fast track designation, breakthrough therapy designation, accelerated 
approval, and priority review designation, have been approved under OMB 
control number 0910-0765.
     Collections of information referred to in the draft 
guidance for industry entitled ``Formal Meetings Between the FDA and 
Sponsors and Applicants for PDUFA Products'' (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm590547.pdf) have been approved under OMB control number 
0910-0429;
     Requirements on content and format of labeling for human 
prescription drug and biological products have been approved under OMB 
control number 0910-0572.
     The submission of new drug applications, including 21 CFR 
314.50(d)(5) (clinical data section) and (d)(6) (statistical section), 
has been approved under OMB control number 0910-0001.
    In accordance with the PRA, before publication of any final 
guidance document, FDA intends to solicit public comment and obtain OMB 
approval for any information collections recommended in this guidance 
that are new or that would represent material modifications to those 
previously approved collections of information found in FDA regulations 
or guidances.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.


[[Page 49400]]


    Dated: September 25, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-21313 Filed 9-28-18; 8:45 am]
 BILLING CODE 4164-01-P

Federal Register / Vol. 83, No. 190 / Monday, October 1, 2018 / Notices 49399

Ave., Bldg. 22, Rm. 2314, Silver Spring, Biologics.’’ It does not establish any ucm464506.pdf) has been approved
MD 20993–0002, 301–796–3400; or rights for any person and is not binding under OMB control number 0910–0843.
Stephen Ripley, Center for Biologics on FDA or the public. You can use an • Collections of information in 21
Evaluation and Research, Food and alternative approach if it satisfies the CFR parts 50 and 56 have been
Drug Administration, 10903 New requirements of the applicable statutes approved under OMB control number
Hampshire Ave., Bldg. 71, Rm. 7301, and regulations. This guidance is not 0910–0755;
Silver Spring, MD 20993–0002, 240– subject to Executive Order 12866.
402–7911. • Collections of information under 21
II. Paperwork Reduction Act of 1995 CFR 56.115 have been approved under
SUPPLEMENTARY INFORMATION:
This draft guidance refers to OMB control number 0910–0130;
I. Background previously approved collections of • Collections of information referred
FDA is announcing the availability of information found in FDA regulations. to in the guidance for industry entitled
a draft guidance for industry entitled These collections of information are ‘‘Expedited Programs for Serious
‘‘Master Protocols: Efficient Clinical subject to review by the Office of Conditions—Drugs and Biologics,’’
Trial Design Strategies to Expedite Management and Budget (OMB) under (available at https://www.fda.gov/ucm/
Development of Oncology Drugs and the Paperwork Reduction Act (PRA) of groups/fdagov-public/@fdagov-drugs-
Biologics.’’ This guidance provides 1995 (44 U.S.C. 3501–3520). gen/documents/document/
advice to sponsors of drugs and FDA has OMB approval under the ucm358301.pdf) including fast track
biologics for treatment of cancer PRA (control number 0910–0014) for the designation, breakthrough therapy
regarding the design and conduct of submission of investigational new drug designation, accelerated approval, and
clinical trials, other than FIH trials, applications (INDs), including priority review designation, have been
intended to simultaneously evaluate protocols, protocol amendments, and approved under OMB control number
more than one investigational drug and/ information amendments, in 21 CFR 0910–0765.
or more than one cancer type within the part 312, subpart B. Sponsors may
same overall trial structure (master request comment and advice on an IND • Collections of information referred
protocols) in adult and pediatric as well as request meetings with FDA to in the draft guidance for industry
cancers. under 21 CFR part 312, subpart C (OMB entitled ‘‘Formal Meetings Between the
There is increased interest in control number 0910–0014). FDA and Sponsors and Applicants for
expediting late-stage drug development Responsibilities of sponsors and PDUFA Products’’ (available at https://
through developing trial designs that investigators (21 CFR part 312, subpart www.fda.gov/ucm/groups/fdagov-
test multiple drugs and/or multiple D) is also covered under OMB control public/@fdagov-drugs-gen/documents/
cancer subpopulations in parallel under number 0910–0014. document/ucm590547.pdf) have been
a single protocol, without a need to approved under OMB control number
In addition, the following collections
develop new protocols for every trial. 0910–0429;
of information that have been approved
The term master protocol is often used • Requirements on content and
by OMB would cover other submissions
to describe the design of such trials, format of labeling for human
discussed in the draft guidance:
with variable terms such as umbrella,
basket, or platform describing specific • Collections of information referred prescription drug and biological
to in the guidance for industry entitled products have been approved under
designs. Examples of trials using master
‘‘Special Protocol Assessment’’ OMB control number 0910–0572.
protocols include the Lung-MAP trial
(NCT02154490), the NCI–MATCH trial (available at https://www.fda.gov/ucm/ • The submission of new drug
(EAY131, NCT02465060), and the groups/fdagov-public/@fdagov-drugs- applications, including 21 CFR
Pediatric MATCH trial (APEC1621, gen/documents/document/ucm498 314.50(d)(5) (clinical data section) and
NCT03155620). In contrast to traditional 793.pdf) have been approved under (d)(6) (statistical section), has been
trial designs, where a single drug is OMB control number 0910–0470; approved under OMB control number
tested in a single disease population in • Collections of information referred 0910–0001.
one clinical trial, master protocols use a to in the guidance for industry entitled
‘‘Establishment and Operation of In accordance with the PRA, before
single infrastructure, trial design, and publication of any final guidance
protocol to simultaneously evaluate Clinical Trial Data Monitoring
Committees’’ (available at https:// document, FDA intends to solicit public
multiple drugs and/or disease comment and obtain OMB approval for
populations in multiple substudies, www.fda.gov/downloads/regulatoryi
nformation/guidances/ucm127073.pdf) any information collections
allowing for efficient and accelerated recommended in this guidance that are
drug development. have been approved under OMB control
number 0910–0581; new or that would represent material
Because of the complexity of these
• Collections of information referred modifications to those previously
trials evaluating multiple drugs and/or
to in the guidance for industry entitled approved collections of information
disease populations and the potential
‘‘Oversight of Clinical Investigations—A found in FDA regulations or guidances.
regulatory impact, it is important that
such trials be well designed and well Risk-Based Approach to Monitoring III. Electronic Access
conducted to ensure patient safety and (available at https://www.fda.gov/
to obtain quality data that may support downloads/Drugs/Guidances/ Persons with access to the internet
drug approval. UCM269919.pdf) has been approved may obtain the draft guidance at either
This draft guidance is being issued under OMB control number 0910–0733; https://www.fda.gov/Drugs/Guidance
amozie on DSK3GDR082PROD with NOTICES

consistent with FDA’s good guidance • Collections of information referred ComplianceRegulatoryInformation/
practices regulation (21 CFR 10.115). to in the ICH guidance for industry Guidances/default.htm, https://
The draft guidance, when finalized, will entitled ‘‘E6(R2) Good Clinical Practice: www.fda.gov/BiologicsBloodVaccines/
represent the current thinking of FDA Integrated Addendum to E6(R1) GuidanceCompliance
on ‘‘Master Protocols: Efficient Clinical (available at https://www.fda.gov/ucm/ RegulatoryInformation/Guidances/
Trial Design Strategies to Expedite groups/fdagov-public/@fdagov-drugs- default.htm, or https://
Development of Oncology Drugs and gen/documents/document/ www.regulations.gov.

VerDate Sep<11>2014 17:50 Sep 28, 2018 Jkt 247001 PO 00000 Frm 00047 Fmt 4703 Sfmt 4703 E:\FR\FM\01OCN1.SGM 01OCN1

Document Created: 2018-09-29 04:26:59
Document Modified: 2018-09-29 04:26:59

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of availability.
Dates		Submit either electronic or written comments on the draft guidance by November 30, 2018 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.
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 20993-0002, 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.
FR Citation		83 FR 49398

83 FR 49398 - Master Protocols: Efficient Clinical Trial Design Strategies To Expedite Development of Oncology Drugs and Biologics; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 190 (October 1, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration