Document ID: FDA-2023-D-1275-0001
Agency: fda
Document Type: Notice
Title: 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To Be Poorly Soluble in Aqueous Media, That Exhibit Little to No Systemic Bioavailability, and Are Locally Acting; Draft Guidance for Industry; Availability
Posted Date: 2023-06-08T04:00Z

[Federal Register Volume 88, Number 110 (Thursday, June 8, 2023)]
[Notices]
[Pages 37551-37552]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-12206]

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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Bioavailability, and Are Locally Acting; Draft Guidance for Industry; 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the availability of a draft guidance for industry (GFI) #279 entitled 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Are Locally Acting; Draft Guidance for Industry.'' This draft guidance 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approach described in this draft guidance uses a combination of in 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DATES: Submit either electronic or written comments on the draft 
guidance by August 7, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-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 draft 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, [email protected].

[[Page 37552]]

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
#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.'' Section 512(c)(2)(A)(vi) of 
the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 
360b(c)(2)(A)(vi)) requires that generic new animal drug products be 
shown to be bioequivalent to the reference listed new animal drug 
(RLNAD), and section 512(n)(1)(E) of the FD&C Act requires that the 
sponsor provide information to show that the proposed product is 
bioequivalent to the RLNAD.
    FDA's Center for Veterinary Medicine (CVM) has issued guidance on 
demonstrating bioequivalence through in vivo studies, and guidance on 
product types that may be eligible for a waiver from the requirement to 
perform in vivo bioequivalence studies, including oral solutions and 
other solubilized forms, parenteral solutions, some topically applied 
dosage forms (see Guidance for Industry #35, ``Bioequivalence 
Guidance'') and TAMAs with APIs that are considered to be water soluble 
(see Guidance for Industry #171, ``Demonstrating Bioequivalence for 
Soluble Powder Oral Dosage Form Products, and Type A Medicated Articles 
Manufactured from Active Pharmaceutical Ingredients Considered To Be 
Soluble in Aqueous Media''). However, these guidance documents do not 
specifically address the unique challenges associated with 
demonstrating bioequivalence of TAMAs containing poorly soluble, 
locally acting APIs. Therefore, this guidance is intended to address 
these unique challenges. In particular, when the TAMA is not a 
candidate for a waiver from the requirement to conduct in vivo blood 
level bioequivalence studies, CVM recommends via this guidance that 
product bioequivalence be demonstrated using alternative test 
approaches to those relying exclusively on animal testing. This draft 
guidance, when finalized, is intended to address these situations.
    This level 1 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 
``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. 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 section 512(n)(1) of the FD&C Act have been approved 
under OMB control number 0910-0669.

III. Electronic Access

    Persons with access to the internet may obtain the draft 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: May 31, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-12206 Filed 6-7-23; 8:45 am]
BILLING CODE 4164-01-P