[Federal Register Volume 88, Number 248 (Thursday, December 28, 2023)]
[Notices]
[Pages 89706-89707]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-28595]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-4177]


Quality Considerations for Topical Ophthalmic Drug Products; 
Revised Draft Guidance for Industry; Availability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the availability of a revised draft guidance for industry entitled 
``Quality Considerations for Topical Ophthalmic Drug Products.'' This 
revised draft guidance discusses certain quality considerations for 
ophthalmic drug products (i.e., gels, ointments, creams, and liquid 
formulations such as solutions, suspensions, and emulsions) intended 
for topical delivery in and around the eye. Specifically, this revised 
draft guidance discusses microbiological considerations; approaches to 
evaluating visible particulate matter, extractables and leachables, and 
impurities and degradation products; use of in vitro drug release/
dissolution testing as an optional quality control strategy for certain 
ophthalmic dosage forms; recommendations for design and delivery and 
dispensing features of container closure systems; and recommendations 
for stability studies. The revised draft guidance applies to marketed 
products including ophthalmic drug products approved under new drug 
applications (NDAs), abbreviated new drug applications (ANDAs), and 
biologics license applications (BLAs), as well as to over-the-counter 
(OTC) monograph drugs, drugs compounded by outsourcing facilities, and 
the drug or biological product constituent part of a combination 
product. This guidance revises the draft guidance for industry of the 
same name issued in October 2023.

DATES: Submit either electronic or written comments on the revised 
draft guidance by February 26, 2024 to ensure that the Agency considers 
your comment on this revised draft guidance before it begins work on 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-4177 for ``Quality Considerations for Topical Ophthalmic 
Drug Products.'' 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 revised 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 revised draft guidance document.

[[Page 89707]]


FOR FURTHER INFORMATION CONTACT: Ranjani Prabhakara, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 6648, Silver Spring, MD 20993-0002, 240-
402-4652.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Quality Considerations for Topical Ophthalmic Drug 
Products.'' This revised draft guidance provides information regarding 
quality considerations for ophthalmic drug products consistent with the 
requirements outlined in section 501(a)(2)(B) of the Federal Food, 
Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)) and 21 CFR 
parts 210 and 211 for all drug products, 21 CFR part 601 for biological 
products, 21 CFR part 4 for combination products, and, for ophthalmic 
drug products with a U.S. Pharmacopeia (USP) monograph, the applicable 
criteria from the USP. The revised draft guidance also provides 
recommendations to industry on the documentation that should be 
submitted in the chemistry, manufacturing, and controls (CMC) section 
of NDAs, ANDAs, and BLAs for certain CMC attributes for ophthalmic drug 
products.
    This revised draft guidance revises the guidance of the same name 
published on October 13, 2023 (88 FR 70997). FDA is revising this draft 
guidance to address microbiological considerations related to product 
sterility for all ophthalmic drug products subject to current good 
manufacturing practice (CGMP) requirements and the prevention of 
contamination of ophthalmic drug products packaged in multidose 
containers, given several recent recalls of ophthalmic drug products 
and instances of consumer injury and death from microbiologically 
contaminated ophthalmic drug products.
    FDA is also revising the draft guidance to clarify its stated 
scope. As originally published, the scope explicitly included NDA, 
ANDA, and BLA products regulated by the Center for Drug Evaluation and 
Research; OTC monograph drugs marketed under section 505G of the FD&C 
Act (21 U.S.C. 355h); and combination products. It was not FDA's 
intention to specifically exclude products that are not marketed under 
an approved application or under section 505G of the FD&C Act; however, 
the draft guidance may have been interpreted that way. Therefore, FDA 
is clarifying that the guidance also applies to other drugs that, while 
also subject to CGMP requirements, are not marketed under a drug 
application, including drugs compounded by outsourcing facilities 
pursuant to section 503B of the FD&C Act (21 U.S.C. 353b).
    This revised draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The revised draft 
guidance, when finalized, will represent the current thinking of FDA on 
``Quality Considerations for Topical Ophthalmic Drug Products.'' 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. Previous Submission of Comments

    In commenting on this revised draft guidance, you do not need to 
reiterate comments that you previously submitted regarding the draft 
guidance issued on October 13, 2023. Your previously submitted comments 
will still be considered. You may instead submit updates to previously 
submitted comments, as needed, and comments related to the new section 
on microbiological considerations and the clarified scope of this 
revised draft guidance.

III. 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 21 CFR part 314 for NDAs and ANDAs have been approved under OMB 
control number 0910-0001. The collections of information in 21 CFR part 
601 for BLAs have been approved under OMB control number 0910-0338. The 
collections of information in 21 CFR parts 210 and 211 pertaining to 
CGMP have been approved under OMB control number 0910-0139. The 
collections of information in 21 CFR 201.56 and 201.57 relating to 
certain prescription product labeling requirements have been approved 
under OMB control number 0910-0572. The collections of information for 
section 351(k) submission of the Public Health Service Act (42 U.S.C. 
262(k)) have been approved under OMB control number 0910-0718. The 
collections of information pertaining to human drug compounding under 
section 503B of the FD&C Act have been approved under OMB control 
number 0910-0858.

IV. Electronic Access

    Persons with access to the internet may obtain the revised 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: December 21, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-28595 Filed 12-27-23; 8:45 am]
BILLING CODE 4164-01-P