[Federal Register Volume 88, Number 111 (Friday, June 9, 2023)]
[Notices]
[Pages 37888-37890]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-12370]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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finalizes the draft guidance ``Clinical Drug Interaction Studies With 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:
     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-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 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 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, 
[email protected].

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 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    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