4164-01-P
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-D-1275]
Demonstrating Bioequivalence for Type A Medicated Articles Containing Active
Pharmaceutical Ingredient(s) Considered To Be Poorly Soluble in Aqueous Media, That
Exhibit Little to No Systemic Bioavailability, and Are Locally Acting; 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 (GFI) #279 entitled “Demonstrating Bioequivalence
for Type A Medicated Articles Containing Active Pharmaceutical Ingredient(s) Considered to be
Poorly Soluble in Aqueous Media, That Exhibit Little to No Systemic Bioavailability, and Are
Locally Acting.” This final guidance describes an approach to satisfy the requirements for the
completion of the Bioequivalence technical section for generic Type A medicated articles
(TAMAs) containing poorly soluble, locally acting, active pharmaceutical ingredients (APIs) that
have little to no systemic absorption, and for which blood level studies are not considered
appropriate to demonstrate product bioequivalence. The suggested approach described in this
guidance uses a combination of in vitro and in vivo data to support a determination of
bioequivalence to address the unique challenges associated with demonstrating bioequivalence of
TAMAs containing poorly soluble, locally acting APIs that have little to no systemic absorption.
DATES: The announcement of the guidance is published in the Federal Register on [INSERT
DATE OF PUBLICATION IN THE FEDERAL REGISTER].
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-2023-D-1275

for “Demonstrating Bioequivalence for Type A Medicated Articles Containing Active
Pharmaceutical Ingredient(s) Considered to be Poorly Soluble in Aqueous Media, That Exhibit

Little to No Systemic Bioavailability, and Are Locally Acting.” 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 guidance to the Policy and Regulations
Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish
Pl., Rockville, MD 20855. 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: Ian Hendricks, Center for Veterinary
Medicine (HFV-172), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855,
240-402-0853, Ian.Hendricks@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of June 8, 2023 (88 FR 37551), FDA published the notice of
availability for a draft guidance entitled “Demonstrating Bioequivalence for Type A Medicated
Articles Containing Active Pharmaceutical Ingredient(s) Considered to be Poorly Soluble in
Aqueous Media, That Exhibit Little to No Systemic Bioavailability, and Are Locally Acting,”
giving interested persons until August 7, 2023, to comment on the draft guidance. In response to
a request for an extension, we extended the comment period for the draft guidance to October 16,
2023 (August 16, 2023, 88 FR 55702).
FDA received two comment submissions on the draft guidance and those comments were
considered as the guidance was finalized. For example, we revised the final guidance to clearly
state that it does not cover APIs that are systemically absorbed because they are already
addressed in other guidances. In addition, several editorial changes were made to improve
clarity. The guidance announced in this notice finalizes the draft guidance dated June 8, 2023.
This level 1 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
“Demonstrating Bioequivalence for Type A Medicated Articles Containing Active
Pharmaceutical Ingredient(s) Considered to be Poorly Soluble in Aqueous Media, That Exhibit

Little to No Systemic Bioavailability, and Are Locally Acting.” 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. The previously approved collections of information
are subject to review by the Office of Management and Budget (OMB) under the Paperwork
Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information in section
512(n)(1) of the Federal Food Drug and Cosmetic Act (21 U.S.C. 360b(n)(1)) have been
approved under OMB control number 0910-0669.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry,
https://www.fda.gov/regulatory-information/search-fda-guidance-documents , or
https://www.regulations.gov.
Dated: June 17, 2024.

Lauren K. Roth,
Associate Commissioner for Policy.

[FR Doc. 2024-13690 Filed: 6/20/2024 8:45 am; Publication Date: 6/21/2024]