Notice2023-20228
Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence; Draft Guidance for Industry; Availability
Primary source
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Published
September 19, 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The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence." This guidance complements the 2019 draft guidance for industry entitled "Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products" (the 2019 Effectiveness draft guidance) and the 1998 guidance for industry entitled "Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products" (the 1998 Effectiveness guidance). Although FDA's evidentiary standard has not changed since 1998, there is a need for more Agency guidance to describe how one adequate and well-controlled clinical investigation and confirmatory evidence can be used to meet the substantial evidence requirement.
Full Text
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<title>Federal Register, Volume 88 Issue 180 (Tuesday, September 19, 2023)</title>
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[Federal Register Volume 88, Number 180 (Tuesday, September 19, 2023)]
[Notices]
[Pages 64445-64446]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-20228]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-D-2318]
Demonstrating Substantial Evidence of Effectiveness Based on One
Adequate and Well-Controlled Clinical Investigation and Confirmatory
Evidence; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled
``Demonstrating Substantial Evidence of Effectiveness Based on One
Adequate and Well-Controlled Clinical Investigation and Confirmatory
Evidence.'' This guidance complements the 2019 draft guidance for
industry entitled ``Demonstrating Substantial Evidence of Effectiveness
for Human Drug and Biological Products'' (the 2019 Effectiveness draft
guidance) and the 1998 guidance for industry entitled ``Providing
Clinical Evidence of Effectiveness for Human Drug and Biological
Products'' (the 1998 Effectiveness guidance). Although FDA's
evidentiary standard has not changed since 1998, there is a need for
more Agency guidance to describe how one adequate and well-controlled
clinical investigation and confirmatory evidence can be used to meet
the substantial evidence requirement.
DATES: Submit either electronic or written comments on the draft
guidance by December 18, 2023 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.
ADDRESSES: You may submit comments on any guidance at any time as
follows:
Electronic Submissions
Submit electronic comments in the following way:
<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-2318 for ``Demonstrating Substantial Evidence of
Effectiveness Based on One Adequate and Well-Controlled Clinical
Investigation and Confirmatory Evidence.'' 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, 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: Eithu Lwin, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 22, Rm. 6236, Silver Spring, MD 20993-0002, 301-796-0728; or Anne
Taylor, Center for Biologics Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7242, Silver
Spring, MD 20993-0002, 240-402-8113.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Demonstrating Substantial Evidence of Effectiveness Based on
One Adequate and Well-Controlled Clinical Investigation and
Confirmatory Evidence.'' This guidance complements the 2019 draft
guidance entitled ``Demonstrating Substantial Evidence of Effectiveness
for Human Drug and
[[Page 64446]]
Biological Products'' issued on December 20, 2019 (84 FR 70196) and the
1998 guidance entitled ``Providing Clinical Evidence of Effectiveness
for Human Drug and Biological Products'' issued on May 15, 1998 (63 FR
27093).
In 1962, Congress required for the first time that new drugs be
shown to be effective as well as safe. A new drug's effectiveness must
be established by substantial evidence. FDA has interpreted this
substantial evidence requirement as generally requiring two adequate
and well-controlled clinical investigations, each convincing on its
own, to establish effectiveness.
In 1997, Congress amended section 505(d) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C. 355(d)) to make clear that FDA
may consider data from one adequate and well-controlled investigation
and confirmatory evidence to constitute substantial evidence if FDA
determines that such data are sufficient to establish effectiveness.
FDA issued the 1998 Effectiveness guidance in response to this
legislative change. In 2019, the Agency concluded that more guidance
was needed on the flexibility in the amount and type of evidence needed
to meet the substantial evidence standard and issued the 2019
Effectiveness draft guidance, which discussed a number of approaches
that can yield evidence that meets the statutory standard for
substantial evidence.
Although both the 1998 Effectiveness guidance and the 2019
Effectiveness draft guidance provide examples of how a single adequate
and well-controlled clinical investigation and confirmatory evidence
can be used to support a marketing application, these guidances are not
intended to provide a comprehensive discussion of meeting the
substantial evidence standard based on one adequate and well-controlled
clinical investigation and confirmatory evidence. Thus, there is a need
for more Agency guidance to describe how one adequate and well-
controlled clinical investigation and confirmatory evidence can be used
to meet the substantial evidence requirement.
When one adequate and well-controlled clinical investigation and
confirmatory evidence are considered together to assess effectiveness,
the quality and quantity of the confirmatory evidence are also
important considerations. Confirmatory evidence should be evidence
generated from quality data derived from an appropriate source. The
quantity of confirmatory evidence needed in a development program will
be impacted by the features of, and results from, the single adequate
and well-controlled clinical investigation that the confirmatory
evidence is intended to substantiate.
This draft guidance describes these considerations in greater
detail. It also provides examples of the types of evidence that could
be considered confirmatory evidence that can be used with one adequate
and well-controlled clinical investigation to demonstrate substantial
evidence of effectiveness. Finally, the draft guidance includes
recommendations for early engagement with the Agency for sponsors who
intend to establish substantial evidence of effectiveness with one
adequate and well-controlled clinical investigation and confirmatory
evidence.
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
``Demonstrating Substantial Evidence of Effectiveness Based on One
Adequate and Well-Controlled Clinical Investigation and Confirmatory
Evidence.'' 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 new 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 parts 58, 312, 314, and 601 have been approved under OMB
control numbers 0910-0119, 0910-0014, 0910-0001, and 0910-0338,
respectively. In addition, the collections of information pertaining to
FDA's guidance entitled ``Formal Meetings Between the FDA and Sponsors
or Applicants of PDUFA Products'' have been approved under OMB control
number 0910-0001.
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">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics</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: September 14, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-20228 Filed 9-18-23; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on September 19, 2023.
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