[Federal Register Volume 75, Number 54 (Monday, March 22, 2010)]
[Notices]
[Pages 13562-13563]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-6171]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0133]


Revised Draft Guidance for Industry on Pharmacokinetics in 
Patients With Impaired Renal Function--Study Design, Data Analysis, and 
Impact on Dosing and Labeling; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a revised draft guidance for industry entitled 
``Pharmacokinetics in Patients With Impaired Renal Function--Study 
Design, Data Analysis, and Impact on Dosing and Labeling.'' The draft 
guidance is intended to assist sponsors planning to conduct studies to 
assess the influence of renal impairment on the pharmacokinetics of an 
investigational drug. It provides recommendations on when studies 
should be conducted to assess the influence of renal impairment on the 
pharmacokinetics of an investigational drug, the design of such 
studies, and how such studies should be carried out.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit written or electronic comments on the draft guidance 
by May 21, 2010.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. Submit written comments on the guidance to the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http://www.regulations.gov. See the SUPPLEMENTARY INFORMATION 
section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Shiew-Mei Huang, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 3188, Silver Spring, MD 20993-0002, 301-
796-1541, or;
    Lei Zhang, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 3106, Silver 
Spring, MD 20993-0002, 301-796-1635.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a revised draft guidance 
entitled ``Pharmacokinetics in Patients With Impaired Renal Function--
Study Design, Data Analysis, and Impact on Dosing and Labeling.'' The 
pharmacokinetics (PK) and pharmacodynamics of drugs primarily 
eliminated through the kidneys may be altered by impaired renal 
function to the extent that the dosage regimen needs to be changed from 
that used in patients with normal renal function. Although the most 
obvious type of change arising from renal impairment is a decrease in 
renal excretion of a drug or its metabolites, changes in renal 
metabolism can also occur. Renal impairment can also adversely affect 
some pathways of hepatic and/or gut drug metabolism and has been 
associated with other changes, such as changes in absorption, plasma 
protein binding, transport, and tissue distribution. These changes may 
be particularly prominent in patients with severely impaired renal 
function and have been observed even when the renal route is not the 
primary route of elimination of a drug. Thus, for most

[[Page 13563]]

drugs that are likely to be administered to patients with renal 
impairment, including drugs that are not primarily excreted by the 
kidney, PK should be assessed in patients with renal impairment to 
provide appropriate dosing recommendations.
    This draft guidance provides recommendations on when studies should 
be conducted to assess the influence of renal impairment on the 
pharmacokinetics of an investigational drug, the design of such 
studies, and how such studies should be carried out.
    In the Federal Register of May 15, 1998 (63 FR 27094), FDA 
announced the availability of a guidance entitled ``Pharmacokinetics in 
Patients With Impaired Renal Function--Study Design, Data Analysis, and 
Impact on Dosing and Labeling.'' The guidance has been revised at this 
time to indicate that a renal impairment study will be recommended for 
all drugs (with a few exceptions). In the original guidance, the agency 
stressed the need to evaluate only drugs that are renally eliminated. A 
second change is that in the 1998 guidance, only the Cockcroft-Gault 
equation was recommended to gauge renal function. The revised draft 
guidance adds the Modification of Diet in Renal Disease equation as 
another possible gauge for renal function and for dose adjustments.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance 
represents the agency's current thinking on conducting PK studies in 
patients with impaired renal function. It does not create or confer any 
rights for or on any person and does not operate to bind FDA or the 
public. An alternative approach may be used if such approach satisfies 
the requirement of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR 201.57 have been 
approved under OMB control number 0910-0572.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances or http://www.regulations.gov.

    Dated: March 16, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-6171 Filed 3-19-10; 8:45 am]
BILLING CODE 4160-01-S