[Federal Register Volume 90, Number 3 (Monday, January 6, 2025)]
[Rules and Regulations]
[Pages 563-565]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-31356]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 211

[Docket No. FDA-2024-D-5374]


Considerations for Complying With 21 CFR 211.110; Draft Guidance 
for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Availability of draft guidance.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Considerations for Complying With 21 CFR 211.110.'' This guidance, 
when finalized, will describe considerations for complying with the 
requirements for ensuring batch uniformity and drug product integrity. 
In addition, this guidance discusses related quality considerations for 
drug products that are manufactured using advanced manufacturing. FDA 
is committed to supporting and enabling pharmaceutical innovation and 
modernization as part of the Agency's mission to protect and promote 
the public health. FDA encourages industry representatives and 
manufactures who are interested in using innovative control strategies 
to contact the Agency.

DATES: Submit either electronic or written comments on the draft 
guidance by April 7, 2025 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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

[[Page 564]]

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-2024-D-5374 for ``Considerations for Complying With 21 CFR 
211.110.'' 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 this 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; the 
Office of Communication, Outreach and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or 
Policy and Regulations Staff, HFV-6, Center for Veterinary Medicine, 
Food and Drug Administration, 7500 Standish Place, 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: Brittany Avaritt, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 6649, Silver Spring, MD 20993-0002, 240-
402-5982; James Myers, Center for Biologics Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bld. 71, Rm. 
7301, Silver Spring, MD 20993-002, 240-402-7911; or Kevin Rice, Center 
for Veterinary Medicine, Food and Drug Administration, 7500 Standish 
Place, Rockville, MD 20855, 240-402-0680.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Considerations for Complying with 21 CFR 211.110.'' This 
guidance, when finalized, will describe considerations for complying 
with the requirements in Sec.  211.110 (21 CFR 211.110) to ensure batch 
uniformity and drug product integrity. In addition, this guidance 
discusses related quality considerations for drug products that are 
manufactured using advanced manufacturing. It also discusses how 
manufacturers can incorporate process models into commercial 
manufacturing control strategies. This guidance applies to the 
manufacture of human drug products, including biological products, and 
animal drug products. This guidance does not apply to the manufacture 
of active ingredients.
    To ensure batch uniformity and drug product integrity, the current 
good manufacturing practice (CGMP) regulations \1\ require, among other 
things, that manufacturing processes are designed and controlled to 
ensure that in-process materials consistently and reliably meet 
predetermined quality requirements.\2\ This guidance explains the 
requirements for drug product manufacturing in Sec.  211.110. This 
guidance also describes considerations for the use of advanced 
manufacturing (e.g., 3D printing, continuous manufacturing) and the use 
of process models as a part of commercial manufacturing control 
strategies. FDA supports the adoption of advanced manufacturing as a 
foundation for improving the overall quality and availability of drug 
products for patients.
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    \1\ See 21 CFR parts 210 and 211. Positron emission tomography 
drug products are subject to CGMP regulations at 21 CFR part 212 and 
are not covered by this guidance.
    \2\ See Sec.  211.110.
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    All manufacturers, regardless of whether they are using advanced 
manufacturing, should apply a scientific- and risk-based approach to 
controlling processes and ensuring drug product quality. This approach 
should be based on robust product and process understanding. Advanced 
manufacturing (such as continuous manufacturing) generally lends itself 
to more extensive understanding and control of the manufacturing 
process; thus, it is generally suitable for implementing process models 
as part of the control strategy. FDA is aware of industry's interest in 
using in-process control strategies that rely solely on process models 
to satisfy the requirements of Sec.  211.110. However, control 
strategies that rely solely on current process models would be 
insufficient to satisfy the requirements of Sec.  211.110.
    FDA is committed to supporting and enabling pharmaceutical 
innovation and modernization as part of the Agency's mission to protect 
and promote the public health. This guidance provides information on 
how process models can be paired with in-process material testing or 
process monitoring to meet current regulatory requirements. As the 
science supporting innovative in-process control tools and methods 
continues to develop, FDA anticipates that these scientific 
advancements can be leveraged to pursue in-process control strategies 
that increasingly rely on process models. FDA encourages industry 
representatives and manufacturers to discuss their proposed innovative 
control strategies with the Agency to help inform future policy 
development.
    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 
``Considerations for Complying With

[[Page 565]]

21 CFR 211.110.'' 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.\3\
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    \3\ The Office of the Federal Register has published this 
document under the category ``Rules and Regulations'' pursuant to 
its interpretation of 1 CFR 5.9(b). We note that the categorization 
as such for purposes of publication in the Federal Register does not 
affect the content or intent of the document. See 1 CFR 5.1(c).
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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 (44 U.S.C. 3501-3521). The collections of information in 
parts 210 and 211 relating to CGMP have been approved under OMB control 
number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain an electronic 
version of the draft 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, https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or 
https://www.regulations.gov.

    Dated: December 23, 2024.
P. Ritu Nalubola,
Associate Commissioner for Policy.
[FR Doc. 2024-31356 Filed 1-3-25; 8:45 am]
BILLING CODE 4164-01-P