Notice2026-17961
Pharmacokinetics in Patients With Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosage; Draft Guidance for Industry; Availability
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Published
September 2, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry titled "Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosage." This guidance assists sponsors in the design and analysis of studies that assess the influence of hepatic impairment on the pharmacokinetics and, where appropriate, the pharmacodynamics of a drug, including therapeutic biological products. When final, this guidance will represent FDA's current thinking. FDA is also withdrawing the guidance for industry titled "Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling" (May 2003), which formerly provided FDA's thinking relating to studies to assess the effect of hepatic impairment on the pharmacokinetics or pharmacodynamics of a drug and recommendations to include hepatic impairment information in labeling.
Full Text
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<title>Federal Register, Volume 91 Issue 169 (Wednesday, September 2, 2026)</title>
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[Federal Register Volume 91, Number 169 (Wednesday, September 2, 2026)]
[Notices]
[Pages 56449-56451]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-17961]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2026-D-8693]
Pharmacokinetics in Patients With Impaired Hepatic Function:
Study Design, Data Analysis, and Impact on Dosage; Draft Guidance for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) is announcing the
availability of a draft guidance for industry titled ``Pharmacokinetics
in Patients with Impaired Hepatic Function: Study Design, Data
Analysis, and Impact on Dosage.'' This guidance assists sponsors in the
design and analysis of studies that assess the influence of hepatic
impairment on the pharmacokinetics and, where appropriate, the
pharmacodynamics of a drug, including therapeutic biological products.
When final, this guidance will represent FDA's current thinking. FDA is
also withdrawing the guidance for industry titled ``Pharmacokinetics in
Patients with Impaired Hepatic Function: Study Design, Data Analysis,
and Impact on Dosing and Labeling'' (May 2003), which formerly provided
FDA's thinking relating to studies to assess the effect of hepatic
impairment on the pharmacokinetics or pharmacodynamics of a drug and
recommendations to include hepatic impairment information in labeling.
DATES: Submit either electronic or written comments on the draft
guidance by December 1, 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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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'').
[[Page 56450]]
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> 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.
<bullet> 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-D-8693 for ``Pharmacokinetics in Patients with Impaired
Hepatic Function: Study Design, Data Analysis, and Impact on Dosage.''
Received comments will be placed in the docket and, except for those
submitted as ``Confidential Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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: Martina Sahre, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD 20993, 301-796-9659,
<a href="/cdn-cgi/l/email-protection#9ed3ffeceaf7f0ffb0cdfff6ecfbdef8faffb0f6f6edb0f9f1e8"><span class="__cf_email__" data-cfemail="cf82aebdbba6a1aee19caea7bdaa8fa9abaee1a7a7bce1a8a0b9">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
titled ``Pharmacokinetics in Patients with Impaired Hepatic Function:
Study Design, Data Analysis, and Impact on Dosage.'' This guidance
assists sponsors in the design and analysis of studies that assess the
influence of impaired hepatic function, herein referred to as hepatic
impairment (HI), on the pharmacokinetics and, where appropriate, the
pharmacodynamics of a drug, including therapeutic biological products.
The liver is a major organ involved in the elimination of drugs
through metabolism and/or through biliary excretion of unchanged drug
or metabolites. Liver disease can change these metabolic and excretory
pathways by impacting drug metabolizing enzymes and transporters. In
addition, the absorption and distribution of drugs can also be affected
by liver disease. In summary, liver disease can lead to changes in a
drug's pharmacokinetics, to a degree necessitating different
recommendations for use of the drug (e.g., a different recommended
dosage in patients with HI). Patients with HI have often been excluded
from clinical trials, even when they are part of the intended target
population. Characterizing the impact of HI on pharmacokinetics during
early clinical drug development and employing modeling and simulation
strategies, where feasible, can facilitate inclusion of patients with
HI in clinical trials.
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
``Pharmacokinetics in Patients with Impaired Hepatic Function: Study
Design, Data Analysis, and Impact on Dosage.'' 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. FDA is also withdrawing the
guidance for industry titled ``Pharmacokinetics in Patients with
Impaired Hepatic Function: Study Design, Data Analysis, and Impact on
Dosing and Labeling'' (68 FR 32531, May 30, 2003), which formerly
provided FDA's thinking relating to studies to assess the effect of HI
on the pharmacokinetics or pharmacodynamics of a drug and
recommendations to include HI information in labeling.
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 312 have been approved under OMB control number 0910-
0014. The collections of information in 21 CFR part 314 have been
approved under OMB control number 0910-0001. The collections of
information in 21 CFR 201.56 and 201.57 relating to certain
prescription product labeling requirements have been approved under OMB
control number 0910-0572.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, https://www.fda.gov/regulatory-
information/search-fda-
[[Page 56451]]
guidance-documents, or https:/www.regulations.gov.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-17961 Filed 9-1-26; 8:45 am]
BILLING CODE 4164-01-P
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