[Federal Register Volume 85, Number 226 (Monday, November 23, 2020)]
[Notices]
[Pages 74737-74738]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-25744]


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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Contraceptives; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Clinical 
Drug Interaction Studies With Combined Oral Contraceptives.'' This 
guidance assists sponsors of investigational new drug applications and 
new drug applications in evaluating the need for and design drug-drug 
interaction (DDI) studies involving combined oral contraceptives (COCs) 
during drug development as well as determining how to communicate the 
results and recommendations from the DDI studies. Specifically, this 
guidance focuses on the conduct of clinical studies to evaluate the DDI 
potential of an investigational drug on a COC, including the need for 
and design of the clinical studies and the interpretation of the study 
results.

DATES: Submit either electronic or written comments on the draft 
guidance by February 22, 2021 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-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 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-

[[Page 74738]]

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: Lauren Milligan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3159, Silver Spring, MD 20903-0002, 301-
796-5008, or [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft 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 draft guidance discusses when 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. 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. 
Based on the study results, specific recommendations for labeling are 
provided. Decision trees regarding whether a DDI study with a COC is 
recommended based on the metabolizing enzyme inhibition or induction 
potential of the investigational drug are also included.
    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 ``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.

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 for submissions of investigational new drug 
applications, new drug applications, and biologic license applications 
in 21 CFR parts 312, 314, and 601 have been approved under OMB control 
numbers 0910-0014; 0910-0001; and 0910-0338, respectively. In addition, 
the submission of prescription drug labeling under 21 CFR 201.56 and 
201.57 has been approved under OMB control number 0910-0572.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.

    Dated: November 13, 2020.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2020-25744 Filed 11-20-20; 8:45 am]
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