Document ID: FDA-2018-D-1456-0012
Agency: fda
Document Type: Notice
Title: Maximal Usage Trials for Topically Applied Active Ingredients Being
Considered for Inclusion in an Over-the-Counter Monograph: Study
Elements and Considerations;Guidance for Industry; Availability
Posted Date: 2019-09-03T04:00Z

[Federal Register Volume 84, Number 91 (Friday, May 10, 2019)]
[Notices]
[Pages 20633-20634]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-09692]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-1798]

Maximal Usage Trials for Topically Applied Active Ingredients 
Being Considered for Inclusion in an Over-the-Counter Monograph: Study 
Elements and Considerations; 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 ``Maximal 
Usage Trials for Topically Applied Active Ingredients Being Considered 
for Inclusion in an Over-the-Counter Monograph: Study Elements and 
Considerations.'' This guidance represents FDA's current thinking on 
the conduct of in vivo absorption trials for topically applied active 
ingredients that are under consideration for inclusion in an over-the-
counter (OTC) monograph.

DATES: The announcement of the guidance is published in the Federal 
Register on May 10, 2019.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances 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-2019-D-1798 for ``Maximal Usage Trials for Topically Applied Active 
Ingredients Being Considered for Inclusion in an Over-the-Counter 
Monograph: Study Elements and Considerations; Guidance for Industry.'' 
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.gpo.gov/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

[[Page 20634]]

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 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: Kristen Hardin, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5443, Silver Spring, MD 20993-0002, 240-
402-4246.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Maximal Usage Trials for Topically Applied Active 
Ingredients Being Considered for Inclusion in an Over-the-Counter 
Monograph: Study Elements and Considerations.'' This guidance 
represents FDA's current thinking on the conduct of in vivo absorption 
trials for topically applied active ingredients that are under 
consideration for inclusion in an OTC monograph. A maximal usage trial 
(MUsT) is a standard approach to assessing the in vivo bioavailability 
of topical drug products. The methodology described in this guidance 
adapts MUsT principles for active ingredients being considered for 
inclusion in an OTC monograph. Because information from a MUsT can help 
identify the potential for systemic exposure to a topically applied 
active ingredient, such information can help inform an FDA 
determination of whether additional safety data are needed to support a 
finding that a topical OTC drug containing that active ingredient is 
generally recognized as safe and effective for its intended use.
    This guidance was written, in part, in response to comments 
submitted to Docket No. FDA-2015-D-4021 for the draft guidance entitled 
``Over-the-Counter Sunscreens: Safety and Effectiveness Data'' (80 FR 
72975, November 23, 2015) and the final guidance that replaced it, 
entitled ``Nonprescription Sunscreen Drug Products--Safety and 
Effectiveness Data,'' (81 FR 84594, November 23, 2016), requesting that 
FDA provide further guidance and details on the MUsT recommended in 
that document. FDA has also recommended a MUsT to address data gaps 
regarding active ingredients under consideration for inclusion in the 
OTC monograph for topical antimicrobial drug products, and in the OTC 
sunscreen monograph rulemaking (see proposed rules ``Safety and 
Effectiveness of Consumer Antiseptics, Topical Antimicrobial Drug 
Products for Over-the-Counter Human Use; Proposed Amendment of the 
Tentative Final Monograph; Reopening of Administrative Record'' (81 FR 
42912, June 30, 2016) and ``Sunscreen Drug Products for Over-the-
Counter Human Use'' (84 FR 6204, February 26, 2019)). This guidance 
provides additional information on the study elements, data analysis, 
and considerations when designing a MUsT for a topically applied active 
ingredient being considered for inclusion in an OTC monograph.
    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 ``Maximal Usage Trials for Topically Applied 
Active Ingredients Being Considered for Inclusion in an Over-the-
Counter Monograph: Study Elements and Considerations.'' 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. Electronic Access

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

    Dated: May 7, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-09692 Filed 5-9-19; 8:45 am]
 BILLING CODE 4164-01-P