[Federal Register Volume 89, Number 53 (Monday, March 18, 2024)]
[Notices]
[Pages 19324-19326]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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draft guidance ``Pharmacokinetics in Patients with Impaired Renal 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:
     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-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 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. 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

[[Page 19326]]

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 
https://www.regulations.gov, https: //www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs.

    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