[Federal Register Volume 85, Number 173 (Friday, September 4, 2020)]
[Notices]
[Pages 55303-55304]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-19597]


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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Design, Data Analysis, and Impact on Dosing; Draft Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 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 This draft guidance revises and 
replaces the draft guidance entitled ``Pharmacokinetics in Patients 
with Impaired Renal Function--Study Design, Data Analysis, and Impact 
on Dosing and Labeling'' (March 2010) and is meant 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 of an investigational drug and how such information 
can impact dosing.

DATES: Submit either electronic or written comments on the draft 
guidance by December 3, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-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 the 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: Lauren Milligan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3159, Silver Spring, MD 20903-0002, 301-
796-5008, or [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Pharmacokinetics in Patients with Impaired Renal Function--
Study Design, Data Analysis, and Impact on Dosing.'' Drugs are 
eliminated from the body by a variety of mechanisms. Most drugs are 
cleared by a combination of some or all of the following pathways: 
Metabolism and transport in the small intestine, metabolism and 
transport in

[[Page 55304]]

the liver, and glomerular filtration and tubular secretion of unchanged 
drug by the kidneys (i.e., renal excretion). If a drug is eliminated 
primarily through renal excretion, then impaired renal function usually 
alters the drug's PK to an extent that the dosage regimen may need to 
be changed from that used in patients with normal renal function. For 
most drugs that are likely to be administered to patients with impaired 
renal function, it is important to characterize PK in subjects with 
impaired renal function to provide appropriate dosing recommendations.
    The safety and efficacy of a drug are generally established for a 
particular dosage regimen (or range of dosage regimens) in late-phase 
clinical trials that enroll patients from the target patient 
population. Frequently, however, individuals with advanced kidney 
disease are explicitly excluded from participation in these studies, 
hindering the assessment of the effects of severely impaired kidney 
function on the PK of a drug or the patient's clinical response. A 
well-planned drug development program can enable prospective dosage 
adjustment based on the observed or expected changes in the PK of a 
drug due to impaired renal function prior to initiating phase 2 or 
phase 3 trials.
    This guidance replaces the 2010 version and provides updated 
recommendations on the following topics:
    (1) When a dedicated study of a drug's PK in subjects with impaired 
renal function is recommended and when it may not be needed;
    (2) The design and conduct of pharmacokinetic studies in subjects 
with impaired renal function;
    (3) Considerations for characterizing a drug's PK in patients 
undergoing intermittent or continuous dialytic therapies;
    (4) The use of pharmacokinetic information from phase 2 and 3 
studies to inform dosing recommendations for patients with renal 
impairment; and
    (5) The analysis and reporting of the results of studies that 
characterize the impact of renal impairment and how these data inform 
dosing.
    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 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

    FDA tentatively concludes that this draft guidance contains no 
collection of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(PRA) (44 U.S.C. 3501-3521) is not required.
    However, this draft guidance refers to previously approved FDA 
collections of information. These collections of information are 
subject to review by OMB under the PRA. The collection of information 
in 21 CFR 201.57 has been approved under OMB control number 0910-0572.

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 or https://www.regulations.gov.

    Dated: August 31, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-19597 Filed 9-3-20; 8:45 am]
BILLING CODE 4164-01-P