Notice2023-12370
Clinical Drug Interaction Studies With Combined Oral Contraceptives; Guidance for Industry; Availability
Primary source
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Published
June 9, 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 final guidance for industry entitled "Clinical Drug Interaction Studies With Combined Oral Contraceptives." This guidance is intended to help sponsors of investigational new drug applications and new drug applications evaluate the need for drug-drug interaction (DDI) studies with combined oral contraceptives (COCs), design such studies, and determine how to communicate DDI study results and risk mitigation strategies to address potential risks associated with increased or decreased exposure of COCs in labeling. The guidance finalizes the draft guidance "Clinical Drug Interaction Studies With Combined Oral Contraceptives" issued on November 23, 2020.
Full Text
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<title>Federal Register, Volume 88 Issue 111 (Friday, June 9, 2023)</title>
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[Federal Register Volume 88, Number 111 (Friday, June 9, 2023)]
[Notices]
[Pages 37888-37890]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-12370]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1848]
Clinical Drug Interaction Studies With Combined Oral
Contraceptives; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``Clinical
Drug Interaction Studies With Combined Oral Contraceptives.'' This
guidance is intended to help sponsors of investigational new drug
applications and new drug applications evaluate the need for drug-drug
interaction (DDI) studies with combined oral contraceptives (COCs),
design such studies, and determine how to communicate DDI study results
and risk mitigation strategies to address potential risks associated
with increased or decreased exposure of COCs in labeling. The guidance
finalizes the draft guidance ``Clinical Drug Interaction Studies With
Combined Oral Contraceptives'' issued on November 23, 2020.
DATES: The announcement of the guidance is published in the Federal
Register on June 9, 2023.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
[[Page 37889]]
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-2020-D-1848 for ``Clinical Drug Interaction Studies With Combined
Oral Contraceptives.'' 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 this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Xinning Yang, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave, Silver Spring, MD 20993, 301-796-7412,
<a href="/cdn-cgi/l/email-protection#cd95a4a3a3a4a3aae394aca3aa8daba9ace3a5a5bee3aaa2bb"><span class="__cf_email__" data-cfemail="461e2f28282f2821681f27282106202227682e2e3568212930">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Clinical Drug Interaction Studies With Combined Oral
Contraceptives.'' COCs can effectively prevent pregnancy; however, the
use of concomitant medications could result in DDIs that affect the
safety and/or efficacy of COCs. For example, the induction of drug
metabolizing enzymes could cause lower levels of progestin and/or
estrogen and compromise the efficacy of COCs, while inhibition of
metabolizing enzymes could cause higher levels of these hormones and
increase the risk of safety events, such as venous thromboembolism.
This guidance discusses when clinical DDI studies with COCs should be
conducted. It also provides recommendations on the design and conduct
of such studies, including but not limited to, the study population,
the choice of COC, study design, pharmacokinetic sampling schedule, and
pharmacodynamic assessments. In addition, this guidance discusses the
interpretation of results from clinical DDI studies with COCs and
whether it is possible to extrapolate the results of such studies to
other COCs. This guidance also provides recommendations to sponsors on
communicating DDI study results and risk mitigation strategies in
labeling to address potential risks associated with increased or
decreased exposure of COCs. A decision tree regarding whether a DDI
study with a COC is recommended based on the metabolizing enzyme
inhibition or induction potential of the investigational drug is also
included.
This guidance finalizes the draft guidance entitled ``Clinical Drug
Interaction Studies With Combined Oral Contraceptives'' issued on
November 23, 2020 (85 FR 74737). FDA considered comments received on
the draft guidance as the guidance was finalized. Changes from the
draft to the final guidance include the addition of more explanations/
scenarios when a DDI study with COCs may or may not be recommended,
clarifications for non-teratogenic drugs that are intended to be used
as a combination therapy with teratogenic drugs, removal of food intake
recommendations, addition of alternative options for choosing COCs, and
more examples of pharmacodynamic parameters for the DDI study.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Clinical Drug Interaction Studies With
Combined Oral Contraceptives.'' 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.
[[Page 37890]]
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR part 312 pertaining to investigational new
drug applications have been approved under OMB control number 0910-
0014. The collections of information in 21 CFR part 314 pertaining to
new drug applications have been approved under OMB control number 0910-
0001. The collections of information in 21 CFR part 601 pertaining to
biologic license applications have been approved under OMB control
number 0910-0338. The collections of information in 21 CFR 201.56 and
201.57 pertaining to the content and format of labeling have been
approved under OMB control number 0910-0572.
III. Electronic Access
Persons with access to the internet may obtain the 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/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: June 6, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-12370 Filed 6-8-23; 8:45 am]
BILLING CODE 4164-01-P
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