[Federal Register Volume 90, Number 228 (Monday, December 1, 2025)]
[Notices]
[Pages 55130-55131]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-21702]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-4678]
Q3E Guideline for Extractables and Leachables; International
Council for Harmonisation; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Q3E
Guideline for Extractables and Leachables'' and a draft supporting
document entitled ``Supporting Documentation: Class 3 Leachable
Monographs.'' The draft guidance and supporting document were prepared
under the auspices of the International Council for Harmonisation of
Technical Requirements for Pharmaceuticals for Human Use (ICH). The
draft guidance presents a holistic framework and process for the
assessment and control of extractables and leachables (E&L) for
pharmaceutical products. The draft guidance builds upon ICH impurity
guidances on new drug substances (ICH Q3A) and new drug products (ICH
Q3B), residual solvents (ICH Q3C), and elemental impurities (ICH Q3D),
as well as DNA reactive (mutagenic) impurities (ICH M7). In addition to
outlining E&L safety assessment principles, the draft guidance includes
draft supporting documentation of Class 3 leachable monographs. The
draft guidance is intended to provide approaches to risk-based
assessment and control of E&L to ensure patient safety and
pharmaceutical product quality.
DATES: Submit either electronic or written comments on the draft
guidance by January 30, 2026 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final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-2025-D-4678 for ``Q3E Guideline for Extractables and Leachables.''
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 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.
[[Page 55131]]
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Edwin Jao, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Silver Spring, MD 20993-0002, 301-796-1684, [email protected]; or
Phillip Kurs, Center for Biologics Evaluation and Research, Food and
Drug Administration, 240-402-7911.
Regarding the ICH: Brooke Dal Santo, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6304, Silver Spring, MD 20993-0002, 301-348-1967,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Q3E Guideline for Extractables and Leachables'' and a draft
supporting document entitled ``Supporting Documentation: Class 3
Leachable Monographs.'' The draft guidance was prepared under the
auspices of ICH. ICH seeks to achieve greater regulatory harmonization
worldwide to ensure that safe, effective, high-quality medicines are
developed, registered, and maintained in the most resource-efficient
manner.
By harmonizing the regulatory requirements in regions around the
world, ICH guidelines enhance global drug development, improve
manufacturing standards, and increase the availability of medications.
For example, ICH guidelines have substantially reduced duplicative
clinical studies, prevented unnecessary animal studies, standardized
the reporting of important safety information, and standardized
marketing application submissions.
The six Founding Members of the ICH are the FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. ICH membership
continues to expand to include other regulatory authorities and
industry associations from around the world (refer to https://www.ich.org/).
ICH works by engaging global regulatory and industry experts in a
detailed, science-based, and consensus-driven process that results in
the development of ICH guidelines. The regulators around the world are
committed to consistently adopting these consensus-based guidelines,
realizing the benefits for patients and for industry.
As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
In August 2025, the ICH Assembly endorsed the draft guideline
entitled ``Q3E Guideline for Extractables and Leachables'' and agreed
that the guideline should be made available for public comment. The
draft guideline is the product of the Quality Expert Working Group of
the ICH. Comments about this draft will be considered by FDA and the
Quality Expert Working Group.
The draft guidance provides a holistic and risk-based framework for
the assessment and control of E&L in pharmaceutical products, expanding
upon existing ICH impurity guidelines. The draft guidance discusses
thresholds for identifying, quantifying, and reporting E&L. The draft
guidance includes draft Class 3 leachable monographs in its supporting
documentation.
This draft guidance has been left in the original ICH format. The
final guidance will be reformatted and edited to conform with FDA's
good guidance practices regulation (21 CFR 10.115) and style before
publication. The draft guidance, when finalized, will represent the
current thinking of FDA on ``Q3E Guideline for Extractables and
Leachables.'' 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.
As we develop final guidance on this topic, FDA will consider
comments on costs or cost savings the guidance may generate, relevant
for Executive Order 14192.
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 part 58 relating to good laboratory practice have been
approved under OMB control number 0910-0119. The collections of
information in 21 CFR parts 210 and 211 relating to current good
manufacturing practice in the manufacture, processing, packing and
storage of finished pharmaceuticals have been approved under OMB
control number 0910-0139. The collections of information in 21 CFR part
314 relating to the submission of new drug applications have been
approved under OMB control 0910-0001. The collections of information in
21 CFR part 601 relating to the submission of biological license
applications have been approved under OMB control number 0910-0338.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
and supporting documentation at https://www.regulations.gov, 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, or
https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
Lowell M. Zeta,
Acting, Deputy Commissioner for Policy, Legislation, and International
Affairs.
[FR Doc. 2025-21702 Filed 11-28-25; 8:45 am]
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