[Federal Register Volume 91, Number 75 (Monday, April 20, 2026)]
[Notices]
[Pages 21000-21002]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-07629]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-6130]
Establishing Impurity Specifications for Antibiotics; Draft
Guidance for Industry; Availability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, Agency, or we) is
announcing the availability of a draft guidance for industry entitled
``Establishing Impurity Specifications for Antibiotics.'' The draft
guidance provides recommendations regarding the establishment of
specifications for organic impurities in antibiotics manufactured by
fermentation and semi-synthesis. This draft guidance applies to
antibiotic drugs subject to approval under new drug applications (NDAs)
and abbreviated new drug applications (ANDAs) and associated type II
drug substance drug master files (DMFs) referenced in antibiotic NDAs
and ANDAs. This guidance also applies to nonprescription antibiotic
drugs, often referred to as over-the-counter (OTC) monograph drugs. By
providing these recommendations, FDA intends to clarify effective
control strategies, support the development of high-quality antibiotic
products, and promote consistency in quality standards.
DATES: Submit either electronic or written comments on the draft
guidance by June 22, 2026.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comment on this draft guidance before it begins work on the final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-6130 for ``Establishing Impurity Specifications for
Antibiotics.'' 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
[[Page 21001]]
``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.gpo.gov/fdsys/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. 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: Ashley Boam, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4192, Silver Spring, MD 20993-0002, 240-
402-6341.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Establishing Impurity Specifications for Antibiotics.'' This
draft guidance provides recommendations for establishing specifications
for organic impurities in antibiotics manufactured by fermentation and
semi-synthesis. These recommendations can be used to establish
consistent standards for impurity testing and ensure that batches of
antibiotic drug products meet appropriate impurity specifications.
This draft guidance applies to antibiotic drugs subject to approval
under NDAs and ANDAs submitted under section 505 of the Federal Food,
Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355), associated type II
drug substance DMFs referenced in antibiotic NDAs and ANDAs, and
nonprescription antibiotic drugs marketed pursuant to section 505G of
the FD&C Act (21 U.S.C. 355h) (often referred to as OTC monograph
drugs). INDs submitted under 21 CFR part 312 should follow the general
principles outlined in the draft guidance.
The recommendations in the draft guidance are not intended to be
applied retroactively (i.e., to antibiotic drugs submitted in
applications or their supplements, or antibiotic drugs marketed before
finalization of this guidance). This is to prevent potential
manufacturing discontinuances or interruptions of marketed antibiotic
drugs that could lead to supply chain disruptions. However, applicants
and manufacturers of marketed antibiotic drugs should consider updating
impurity specifications in accordance with this draft guidance when
making major changes, such as replacing a source of active
ingredient(s), and to ensure the drugs are manufactured in compliance
with Current Good Manufacturing Practice (CGMP) requirements.
The ICH guidances for industry Q3A(R) Impurities in New Drug
Substances (June 2008) and Q3B(R2) Impurities in New Drug Products
(August 2006) provide recommendations on thresholds for the
identification, reporting, and qualification of impurities and
degradation products in new drug substances and drug products using
drug substances that are produced by chemical synthesis. However,
current guidances do not provide recommendations for the control of
impurities and degradation products in fermentation and semi-synthetic
products, including certain antibiotics manufactured from these
processes. Antibiotics manufactured by fermentation or semi-synthesis
are typically more complex than those produced solely by chemical
synthesis, often containing a mixture of the active ingredient and
impurities. The active ingredient is generally not a single molecular
entity but rather a collection of structurally related, biologically
active analogs that together define the active ingredient. To address
this gap, the draft guidance provides recommendations on the
identification, qualification, and control of impurities and
degradation products in fermentation-based and semi-synthetic
antibiotics. The principles described in ICH Q3A(R), ICH Q3B(R2), and
ICH M7(R2) should apply to antibiotics manufactured by fermentation and
semi-synthesis. Antibiotic drugs that have United States Pharmacopeia
(USP) monographs must meet the requirements outlined in the respective
USP monographs for the drug substance and the drug product (section
501(b) of the FD&C Act).
The 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 ``Establishing
Impurity Specifications for Antibiotics.'' 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 parts 210 and 211 pertaining to CGMP requirements have been
approved under OMB control number 0910-0139. The collections of
information in 21 CFR parts 312 and 314 have been approved under OMB
control numbers 0910-0014 and 0910-0001, respectively. The collections
of information pertaining to 21 CFR part 201 Subpart C pertaining to
over-the-counter drug product labeling have been approved under OMB
control number 0910-0340.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-
information/search-fda-
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guidance-documents, or https://www.regulations.gov.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-07629 Filed 4-17-26; 8:45 am]
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