[Federal Register Volume 90, Number 175 (Friday, September 12, 2025)]
[Notices]
[Pages 44194-44196]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-17698]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-D-3031]


Alternative Tools: Assessing Drug Manufacturing Facilities 
Identified in Pending Applications; 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 final guidance for industry entitled 
``Alternative Tools: Assessing Drug Manufacturing Facilities Identified 
in Pending Applications.'' This guidance provides information to 
applicants on how FDA intends to use alternative tools to assess drug 
manufacturing facilities identified in a marketing application (i.e., a 
new drug application (NDA), an abbreviated new drug application (ANDA), 
a biologics license application (BLA), or a supplement to any of these 
types of applications). As part of the negotiations relating to the 
reauthorization of the Prescription Drug User Fee Act (PDUFA) and the 
Biosimilar User Fee Act (BsUFA), as described in ``PDUFA 
Reauthorization Performance Goals and Procedures Fiscal Years 2023 
Through 2027'' (PDUFA VII commitment letter) and ``Biosimilar 
Biological Product Reauthorization Performance Goals and Procedures for 
Fiscal Years 2023 Through 2027'' (BsUFA III commitment letter), FDA 
agreed to issue guidance on the use of alternative tools to assess 
manufacturing facilities named in pending applications and to 
incorporate best practices from the use of such tools during the 
Coronavirus Disease 2019 (COVID-19) pandemic. This guidance finalizes 
the draft guidance of the same title issued on September 22, 2023.

DATES: The announcement of the guidance is published in the Federal 
Register on September 12, 2025.

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:

[[Page 44195]]

     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-3031 for ``Alternative Tools: Assessing Drug Manufacturing 
Facilities Identified in Pending Applications.'' 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 
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 guidance document.

FOR FURTHER INFORMATION CONTACT: Jessica Dunn, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 4214, Silver Spring, MD 20993-0002, 240-
402-8985; or Phillip Kurs, Center for Biologics Evaluation and 
Research, Food and Drug Administration, 240-402-0467.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Alternative Tools: Assessing Drug Manufacturing Facilities 
Identified in Pending Applications.'' This guidance provides 
information to applicants on how FDA intends to use alternative tools 
to assess drug manufacturing facilities identified in an NDA, an ANDA, 
a BLA, or a supplement to any of these types of applications. As part 
of the negotiations relating to the reauthorization of BsUFA and PDUFA, 
FDA agreed to issue guidance on the use of alternative tools to assess 
manufacturing facilities named in pending applications and to 
incorporate best practices from the use of such tools during the COVID-
19 pandemic. This guidance, within the context of approval and 
licensure decisions by FDA, describes the use of alternative tools to 
assess manufacturing facilities identified in an NDA, an ANDA, or a BLA 
to establish that these facilities meet the applicable requirements, 
including under section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 
351(a)(2)(B)) and either section 505 of the FD&C Act (21 U.S.C. 355) or 
section 351 of the Public Health Service Act (42 U.S.C. 262). FDA 
considered the applicability of Executive Order 14192, per OMB guidance 
in M-25-20, and finds this action to be deregulatory in nature.
    During the pandemic, FDA expanded its use of alternative tools to 
evaluate drug manufacturing facilities to support regulatory decision 
making when facility inspections were not feasible. The following 
alternative tools were used during the COVID-19 public health 
emergency:
     Requesting records and other information, pursuant to 
section 704(a)(4) of the FD&C Act (21 U.S.C. 374(a)(4)), directly from 
facilities and other entities subject to inspection
     Performing remote interactive evaluations (e.g., remote 
live streaming video of operations, teleconferences, screen sharing)
     Requesting existing inspection reports and other 
information from trusted foreign regulatory partners through mutual 
recognition agreements and other agreements
    FDA has strategically used these tools within the context of 
decisions related to preapproval inspections (PAIs) or prelicense 
inspections (PLIs) to maximize facility assessment efficiency as part 
of appropriate, risk-based assessments. Given the success of these 
innovative approaches, FDA intends to continue risk-based use of these 
alternative tools and to apply certain virtual technological 
capabilities within a specific inspectional context defined within this 
guidance. When used in advance or in lieu of PAIs and PLIs or to 
support PAIs and PLIs, the appropriate use of these approaches will 
help FDA maintain operational flexibility to support timely facility 
evaluations and application decisions.
    This guidance finalizes the draft guidance entitled ``Alternative 
Tools: Assessing Drug Manufacturing Facilities Identified in Pending 
Applications'' issued on September 22, 2023 (88 FR 65396). FDA 
considered comments received on the draft guidance as the guidance was 
finalized. Based on the comments received, FDA updated the guidance 
with additional clarification on: (1) the recommended timeframe for 
facilities to respond to section 704(a)(4) of the FD&C Act records 
requests; (2) the timeframes for when facilities may expect to receive 
requests from FDA to use a remote subject matter expert (SME) during an 
inspection; (3) Agency efforts to coordinate logistical approaches and 
technologies with facilities regarding FDA's use of alternative tools; 
and (4) the effect of a facility declining to allow FDA to use a remote 
SME or when a facility is unable to support the virtual interaction 
with a remote SME.
    This 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 ``Alternative Tools:

[[Page 44196]]

Assessing Drug Manufacturing Facilities Identified in Pending 
Applications.'' 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 21 CFR parts 210 and 211 relating to current good manufacturing 
practice requirements and electronic records and signatures have been 
approved under OMB control numbers 0910-0139 and 0910-0303, 
respectively. The collections of information in 21 CFR part 314 
relating to the submission of NDAs and ANDAs have been approved under 
OMB control number 0910-0001. The collections of information in 21 CFR 
part 601 relating to the submission of BLAs have been approved under 
OMB control number 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, 
https:/www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-17698 Filed 9-11-25; 8:45 am]
BILLING CODE 4164-01-P