[Federal Register Volume 91, Number 41 (Tuesday, March 3, 2026)]
[Notices]
[Pages 10397-10399]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-04196]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-N-0809]
Recommendations on Scale-Up and Postapproval Changes Guidances
for Industry; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for information and comments.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing the opening of a public docket to solicit information and
comments on the Agency's series of guidances for industry on scale-up
and postapproval changes (SUPAC) for specific dosage forms.
Specifically, we are seeking comment on the following guidances for
industry: ``Immediate Release Solid Oral Dosage Forms Scale-Up and
Postapproval Changes: Chemistry, Manufacturing, and Controls, In Vitro
Dissolution Testing, and In Vivo Bioequivalence Documentation'' (SUPAC-
IR); ``SUPAC-IR Questions and Answers about SUPAC-IR Guidance'' (SUPAC-
IR Q&A); ``Nonsterile Semisolid Dosage Forms Scale-Up and Postapproval
Changes: Chemistry, Manufacturing, and Controls; In Vitro Release
Testing and In Vivo Bioequivalence Documentation'' (SUPAC-SS); ``SUPAC-
MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval
Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution
Testing and In Vivo Bioequivalence Documentation'' (SUPAC-MR); and
``SUPAC: Manufacturing Equipment Addendum'' (SUPAC-MEA). The Agency is
seeking public information and comment on the continued utility of and
suggestions for potential revisions to the recommendations in these
guidances.
DATES: Submit either electronic or written comments on the notice by
June 1, 2026 to ensure that the Agency considers your comment on these
guidance documents before it begins work on any revisions.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of June 1, 2026. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
[[Page 10398]]
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-2026-N-0809] for ``Recommendations on Scale-Up and Postapproval
Changes Guidances for Industry; Request for Comments.'' Received
comments, those filed in a timely manner (see ADDRESSES), 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.
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, 301-
796-6341, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
After a series of workshops with interested partners and FDA-
sponsored research in the 1990s, FDA's Center for Drug Evaluation and
Research developed a risk-based approach for implementing chemistry,
manufacturing, and controls (CMC) changes that could affect identity,
strength, quality, purity, or potency of a drug product as these
factors may relate to the safety or effectiveness of the drug product.
This risk-based approach was first explained in the SUPAC guidances,
which describe the recommended testing and documentation for component
and composition changes, manufacturing process and equipment changes,
manufacturing scale changes, and manufacturing site changes. The intent
of this risk-based approach was to reduce the regulatory burden of
obtaining FDA approval for certain CMC changes to approved applications
that were not likely to affect the identity, strength, quality, purity,
or potency of a drug product and, therefore, the safety or
effectiveness of the drug product.
In November 1997, the risk-based approach for implementing CMC
changes that was introduced in the SUPAC guidances was codified in
section 116 of the Food and Drug Administration Modernization Act
(FDAMA) (Pub. L. 105-115). Section 116 of FDAMA amended the Federal
Food, Drug, and Cosmetic Act (FD&C Act) by adding section 506A (21
U.S.C. 356a), which describes requirements and procedures for making
and reporting any CMC changes to approved applications, including new
and abbreviated new drug applications. On April 8, 2004, FDA issued the
final rule to implement section 506A of the FD&C Act (69 FR 18728). The
final rule requires applicants to assess the effects of CMC changes on
the identity, strength, quality, purity, and potency of a drug product
as they may relate to the safety and effectiveness of the product.
Further, the final rule sets forth submission requirements, based on
the characterization of the CMC change (e.g., major, moderate, or
minor), that must be met before the distribution of the product made
using the change (see 21 CFR 314.70). In the preamble to the final
rule, FDA acknowledged that when section 116 of FDAMA was written it
was anticipated that ``the science of manufacturing would evolve over
time,'' and that ``FDA may, by regulation or guidance, change the
designation of a particular category of change from major to nonmajor
or vice versa'' (69 FR 18728 at 18729). The final rule was effective on
June 22, 2004.
Except for SUPAC-MEA, which was updated in 2014, the SUPAC
guidances were finalized between 1995 and 1997. Since then, the use and
evolution of risk assessment tools in pharmaceutical development has
enhanced the ability to identify, categorize, and control risks
associated with a CMC change that impact product quality. We have
determined that the SUPAC guidances may benefit from additional public
comment on the topics outlined in this notice to ensure that these
guidances align with current expectations, risk assessment strategies,
and contemporary scientific and technical considerations.
II. Issues for Consideration and Requested Information and Comments
Despite the time that has elapsed since the SUPAC guidances were
implemented, the core principle of a risk-based approach for
implementing
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CMC changes as described in the guidances remains relevant. The SUPAC
guidances assist in reducing the number of CMC changes that require
approval of a supplemental application, which can minimize delays in
distribution of the product, give companies greater control over their
production resources, and result in significant net savings to
industry. In addition, the SUPAC guidances allow FDA to focus resources
on those changes that pose the greatest risk to product quality thereby
improving efficiency and promoting timely continual improvement in
accordance with current good manufacturing practice. We acknowledge,
however, that the effectiveness of the SUPAC guidances may be impacted
by subsequent guidances (e.g., ICH Q9(R1) and ICH Q12)), where
particular recommendations in those guidances either supersede or
potentially conflict with certain recommendations in the SUPAC
guidances. For example, the principles described in ICH Q12 (e.g., how
enhanced development can inform the nature and extent of established
conditions, further elaboration on change management as an aspect of
the pharmaceutical quality system) are intended to enhance industry's
ability to manage many CMC changes with greater efficiency and with
less regulatory oversight prior to implementation of the change.
Accordingly, FDA is considering updating the SUPAC guidances to improve
their utility and effectiveness in light of evolving science, to ensure
they continue to reflect the Agency's current thinking on risk-based
approaches to CMC changes, and to enable manufacturers to more
effectively evaluate changes within their quality systems prior to
submitting a CMC change for evaluation.
Interested persons are invited to provide detailed comments and
information related to the contents of this notice. To facilitate
input, we have developed the following questions about the SUPAC
guidances:
1. How are the recommendations provided in the SUPAC guidances
still helpful and meaningful to regulated industry?
a. Are there sections of the SUPAC guidances that are particularly
beneficial and are important to retain, either partially or in their
entirety, because they reflect current risk-based approaches and are
currently being referenced by applicants to support CMC changes?
b. Are the risk-based principles described in the SUPAC guidances
being used to help inform applicants in other ways in addition to
supporting CMC changes?
2. What challenges do you have when interpreting or applying the
recommendations in the SUPAC guidances?
a. Are there sections of the SUPAC guidances that should be removed
because they are no longer relevant or meaningful?
b. When referencing the SUPAC guidances for recommendations on a
CMC change, are you able to effectively evaluate changes within your
quality system and readily identify both the type and the corresponding
level of change (i.e., major, moderate, or minor) based on the
information provided in the SUPAC guidances? If not, please specify
what challenges you have when making this determination.
c. Are there areas of overlap or inconsistencies among the various
SUPAC guidances or in other FDA guidances on CMC changes that may cause
confusion when trying to apply the recommendations? Please specify the
areas of overlap or inconsistencies.
3. How can FDA provide clarity on the recommendations provided in
the SUPAC guidances? For example:
a. Should FDA consider reorganizing the content in the SUPAC
guidances, for example, by either combining the multiple SUPAC
guidances into a single guidance, or separating topics in the
individual guidances, so that recommendations are easier to interpret
and apply?
b. Are there recommendations from other FDA guidances, for example,
the studies described in the draft guidance for industry titled
``Physicochemical and Structural (Q3) Characterization of Topical Drug
Products Submitted in ANDAs'' (87 FR 64230),\1\ that if included in the
SUPAC guidances, might help to reduce regulatory burden?
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\1\ When final, this guidance will represent the FDA's current
thinking on this topic. For the most recent version of a guidance,
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
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c. How might the recommendations in the SUPAC guidances be better
aligned with current risk assessment and postapproval lifecycle
management principles and tools (e.g., postapproval change management
protocols, established conditions)?
4. Are there new topics that should be added to the SUPAC
guidances?
These questions are not meant to be exhaustive, and we are also
interested in any other pertinent information interested persons would
like to share on this topic. This feedback will help inform the
Agency's general policy development direction. FDA encourages
commenters to provide the specific rationale and basis for their
comments, including any available supporting data and information.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-04196 Filed 3-2-26; 8:45 am]
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