[Federal Register Volume 87, Number 204 (Monday, October 24, 2022)]
[Notices]
[Pages 64230-64232]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-23016]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-1864]


Physicochemical and Structural (Q3) Characterization of Topical 
Drug Products Submitted in Abbreviated New Drug Applications; Draft 
Guidance for Industry, Availability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the availability of a draft guidance for industry entitled 
``Physicochemical and Structural (Q3) Characterization of Topical Drug 
Products Submitted in ANDAs.'' This draft guidance is intended to 
assist applicants who submit abbreviated new drug applications (ANDAs) 
for liquid-based and/or other semisolid products applied to the skin, 
including integumentary and mucosal (e.g., vaginal) membranes (referred 
to as ``topical products''). This draft guidance document provides 
recommendations for physicochemical and structural (collectively, 
``Q3'') characterizations that can be used to identify the dosage form 
of a proposed generic (test) topical product, and to describe 
properties of the drug product that may be critical to its performance 
(to support a demonstration of bioequivalence (BE)).

DATES: Submit either electronic or written comments on the draft 
guidance by December 23, 2022 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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

[[Page 64231]]

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-2022-D-1864 for ``Physicochemical and Structural (Q3) 
Characterization of Topical Drug Products Submitted in 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 the office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Susan Levine, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 1674, Silver Spring, MD 20993-0002, 240-
402-7936.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Physicochemical and Structural (Q3) Characterization of 
Topical Drug Products Submitted in ANDAs.'' This draft guidance is 
intended to assist applicants who submit ANDAs for liquid-based and/or 
other semisolid products applied to the skin, including integumentary 
and mucosal (e.g., vaginal) membranes. This draft guidance document 
provides recommendations for physicochemical and structural 
(collectively, ``Q3'') characterizations that can be used: (1) to 
identify the dosage form of a proposed generic (test) topical product 
and (2) to describe properties of the drug product that may be critical 
to its performance (to support a demonstration of BE). This draft 
guidance does not address Q3 characterization of topical products for 
purposes of product quality control.
    Basic Q3 characterization of a topical product can be used to 
describe its dosage form (e.g., an emulsion). The nomenclature used to 
describe the dosage form of topical products (e.g., solutions, 
suspensions, gels, lotions, creams, shampoos, ointments, pastes, etc.) 
is not precisely defined by a systematic classification of the 
compositional, physicochemical, or structural attributes of the drug 
product. Consequently, for topical products, it may not be possible to 
infer the Q3 attributes of a particular dosage form based upon the 
dosage form nomenclature.
    Comprehensive Q3 characterization of a topical product can be used 
to establish a detailed profile of Q3 attributes that specifically 
describes the nature of that product and identifies a collection of 
attributes that describe the arrangement of matter (e.g., the 
polymorphic form(s) of the active ingredient(s) and/or the pH of the 
drug product) that may modulate the systemic or local availability of 
the active ingredient(s) from the product. Because Q3 characterization 
describes essential attributes of a drug product that may be critical 
to its performance, differences in Q3 attributes between a test product 
and the reference standard selected by FDA can indicate a risk that the 
differences may impact the respective bioavailability and/or BE of the 
two products. Conversely, a demonstration that there are no differences 
in Q3 attributes between a test and reference standard substantially 
mitigates the risk of potential failure modes for BE that may otherwise 
arise from any differences in Q3 attributes.
    This draft guidance provides recommendations on the types of 
characterizations that constitute a basic and comprehensive Q3 
characterization. This draft guidance also describes the concepts of 
``sameness,'' ``similarity,'' and ``difference'' in comparing Q3 
characterizations of two topical products, and how a showing of ``Q3 
sameness,'' ``Q3 similarity,'' or ``Q3 difference'' between a test 
topical product and the reference standard may impact what additional 
evidence may be recommended to demonstrate BE, as part of a comparative 
product characterization-based approach.
    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 
``Physicochemical and Structural (Q3) Characterization of Topical Drug 
Products Submitted in 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

[[Page 64232]]

it satisfies the requirements of the applicable statutes and 
regulations.

II. Paperwork Reduction Act of 1995

    While this 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 for the submission of ANDAs have been approved under OMB 
control number 0910-0001. Applicant submission of controlled 
correspondence related to generic drug development and FDA approval is 
approved under OMB control number 0910-0797. The collections of 
information that support Good Laboratory Practice (GLP) for Nonclinical 
Laboratory Studies have been approved under OMB control number 0910-
0119. The collections of information in 21 CFR part 320 for 
``Investigational New Drug Safety Reporting Requirements for Human Drug 
and Biological Products and Safety Reporting Requirements for 
Bioavailability and Bioequivalence Studies in Humans'' have been 
approved under OMB control number 0910-0014. The recordkeeping 
requirement for Current Good Manufacturing Practice (CGMP) sample 
retention in 21 CFR 211.170 has been approved under OMB control number 
0910-0139.

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: October 18, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-23016 Filed 10-21-22; 8:45 am]
BILLING CODE 4164-01-P


