Notice2024-05683
Pharmacokinetics in Patients With Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing; Guidance for Industry; Availability
Primary source
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Published
March 18, 2024
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Pharmacokinetics in Patients with Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing." In general, drug development programs should be conducted so that when products are approved, the labeling provides appropriate dosing recommendations for patients with renal impairment. This guidance is intended to assist sponsors in the design and analysis of studies that assess the influence of impaired renal function on the pharmacokinetics (PK) and/ or pharmacodynamics (PD) of an investigational drug and addresses how such information can inform the labeling. This guidance finalizes the draft guidance "Pharmacokinetics in Patients with Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing" issued on September 4, 2020.
Full Text
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<title>Federal Register, Volume 89 Issue 53 (Monday, March 18, 2024)</title>
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[Federal Register Volume 89, Number 53 (Monday, March 18, 2024)]
[Notices]
[Pages 19324-19326]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-05683]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-D-0133]
Pharmacokinetics in Patients With Impaired Renal Function--Study
Design, Data Analysis, and Impact on Dosing; 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 final guidance for industry entitled
``Pharmacokinetics in Patients with Impaired Renal Function--Study
Design, Data Analysis, and Impact on Dosing.'' In general, drug
development programs should be conducted so that when products are
approved, the labeling provides appropriate dosing recommendations for
patients with renal impairment. This guidance is intended to assist
sponsors in the design and analysis of studies that assess the
influence of impaired renal function on the pharmacokinetics (PK) and/
or pharmacodynamics (PD) of an investigational drug and addresses how
such information can inform the labeling. This guidance finalizes the
draft guidance ``Pharmacokinetics in Patients with Impaired Renal
Function--Study Design, Data Analysis, and Impact on Dosing'' issued on
September 4, 2020.
DATES: The announcement of the guidance is published in the Federal
Register on March 18, 2024.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
[[Page 19325]]
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'').
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-2010-D-0133 for ``Pharmacokinetics in Patients with Impaired Renal
Function--Study Design, Data Analysis, and Impact on Dosing.'' 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 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. See the
SUPPLEMENTARY INFORMATION section for electronic access to the guidance
document.
FOR FURTHER INFORMATION CONTACT: Martina Sahre, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., WO51/2114, Silver Spring, MD 20993-0002, 301-796-9659.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a final guidance for industry
entitled ``Pharmacokinetics in Patients with Impaired Renal Function--
Study Design, Data Analysis, and Impact on Dosing.'' The kidneys are
involved in the elimination of many drugs, where the degree of renal
excretion of unchanged drug and/or metabolites is the net result of
glomerular filtration, tubular secretion, tubular reabsorption, and to
a lesser degree metabolism. If a drug is eliminated primarily through
renal excretion, then impaired renal function often alters the drug's
PK to an extent that a change in the dosage from that used in patients
with normal renal function should be considered. Literature reports
indicate that impaired renal function can alter some drug metabolism
and transport pathways in the liver and gut, thus there is the
potential for renal impairment to also affect drugs that are
predominantly cleared nonrenally. For these reasons, it is important to
characterize a drug's PK in subjects with impaired renal function to
provide appropriate dosage recommendations.
The safety and effectiveness of a drug are generally established
for specific dosage regimens in late-phase clinical trials that enroll
patients from the intended target patient population. Sometimes,
individuals with impaired renal function are explicitly excluded from
participation in these trials. Drug development programs should include
an early characterization of the effect of impaired renal function on a
drug's PK, with the goal of enabling the inclusion of this population
in late-phase trials by allowing appropriate prospective dosage
adjustment.
This guidance finalizes the draft guidance of the same title issued
on September 4, 2020 (85 FR 55303). Revisions to the draft guidance
include an expansion of the section on renal replacement therapies,
especially the language related to continuous renal replacement
therapy. Further revisions include an edit to the classification stages
for the purpose of enrolling into a stand-alone renal impairment study.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Pharmacokinetics in Patients with Impaired
Renal Function--Study Design, Data Analysis, and Impact on Dosing.'' 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.
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
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Budget (OMB) under the Paperwork Reduction Act (44 U.S.C. 3501-3521).
The collections of information in 21 CFR 201.57 pertaining to certain
prescription drug labeling have been approved under OMB control number
0910-0572. The collections of information in 21 CFR part 312 pertaining
to the submission of investigational new drug applications have been
approved under OMB control number 0910-0014. The collections of
information in 21 CFR part 314 pertaining to the submission of new drug
applications have been approved under OMB control number 0910-0001. The
collections of information in 21 CFR part 601 pertaining to biologics
license applications have been approved under OMB control number 0910-
0338.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<a href="https://www.regulations.gov">https://www.regulations.gov</a>, https: //<a href="http://www.fda.gov/regulatory-information/search-fda-guidance-documents">www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <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>.
Dated: March 12, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-05683 Filed 3-15-24; 8:45 am]
BILLING CODE 4164-01-P
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