[Federal Register Volume 88, Number 71 (Thursday, April 13, 2023)]
[Notices]
[Pages 22457-22459]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07769]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3546]


Assessing the Irritation and Sensitization Potential of 
Transdermal and Topical Delivery Systems for ANDAs; Revised Draft 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

[[Page 22458]]


ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a revised draft guidance for industry entitled 
``Assessing the Irritation and Sensitization Potential of Transdermal 
and Topical Delivery Systems for ANDAs.'' This revised draft guidance 
provides recommendations for the design and conduct of studies to 
evaluate the in vivo skin irritation and sensitization (I/S) potential 
of a proposed transdermal or topical delivery system (collectively 
referred to as TDS). The recommendations in this revised draft guidance 
relate to studies submitted in support of an abbreviated new drug 
application (ANDA). The revised draft guidance is intended to clarify 
FDA's recommendations and expectations related to in vivo skin I/S 
studies. This guidance revises the October 2018 draft guidance entitled 
``Assessing the Irritation and Sensitization Potential of Transdermal 
and Topical Delivery Systems for ANDAs.''

DATES: Submit either electronic or written comments on the draft 
guidance by June 12, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:
     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-2018-D-3546 for ``Assessing the Irritation and Sensitization 
Potential of Transdermal and Topical Delivery Systems for ANDAs.'' 
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 20993-0002. 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: Melissa Mannion, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 1611, Silver Spring, MD 20993-0002, 301-
796-2747.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Assessing the Irritation and Sensitization 
Potential of Transdermal and Topical Delivery Systems for ANDAs.'' This 
guidance revises the draft guidance entitled ``Assessing the Irritation 
and Sensitization Potential of Transdermal and Topical Delivery Systems 
for ANDAs'' that was published in the Federal Register on October 10, 
2018 (83 FR 50945). FDA received eight comments on the draft guidance, 
which were considered before publication of this revised draft 
guidance.
    The components and composition of a TDS formulation, including the 
nature of the drug substance and/or the occlusivity of the TDS 
materials, in conjunction with other factors such as the environmental 
humidity or the condition of the skin, may have the potential to 
irritate the skin or lead to a sensitization reaction. Such reactions 
can be unpleasant to the patient and may affect patient compliance, 
skin permeability, and/or adhesion of the TDS to the skin. The 
collective consequence of these potential effects could create 
uncertainty about the resulting drug delivery profile and uncertainty 
about the rate and extent of drug absorption from the TDS. Therefore, 
when appropriate, applicants should perform a comparative assessment of 
the test (T) and reference

[[Page 22459]]

(R) TDS products using an appropriately designed skin I/S study with 
human subjects to demonstrate that the potential for a skin irritation 
or sensitization reaction with the T TDS is no worse than the reaction 
observed with the R TDS.
    This revised draft guidance provides the following updates to the 
original draft guidance:
    (1) Clarifies recommendations for the design and conduct of studies 
to evaluate the in vivo skin I/S potential of a proposed TDS.
    (2) Clarifies when an in vivo study to assess the sensitization 
potential of a TDS product may not be needed.
    (3) Provides guidance to applicants intending to utilize 
alternative scoring scales or alternative approaches to compare 
irritation and sensitization between the T and R TDS.
    The recommendations in this revised draft guidance relate to 
studies submitted in support of an ANDA. The Agency is seeking comments 
on the recommendations reflected in the revised draft guidance 
announced in this notice. In addition, FDA invites comments on the 
scoring scales and any alternative approaches, including those 
recommended by international regulatory agencies, that may have been 
used for the comparative assessment of the I/S potential for proposed 
generic TDS products. FDA also specifically invites comments regarding 
the comparative assessment of sensitization itself, i.e., whether there 
are clinical scenarios where a comparative sensitization assessment may 
be uninformative when conducted in addition to a comparative irritation 
assessment.
    This revised 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 
``Assessing the Irritation and Sensitization Potential of Transdermal 
and Topical Delivery Systems for ANDAs.'' 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 revised draft 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 314 relating to the 
submission of abbreviated new drug applications have been approved 
under OMB control number 0910-0001. The collections of information 
relating to good clinical practice have been approved under OMB control 
number 0910-0843.

III. Electronic Access

    Persons with access to the internet may obtain the draft 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: April 7, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-07769 Filed 4-12-23; 8:45 am]
BILLING CODE 4164-01-P