[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Revised Draft Guidance for Industry on Pharmacokinetics in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availability of a revised draft guidance for industry entitled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 The draft
guidance is intended to assist sponsors planning to conduct studies to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draft guidance before it begins work on the final version of the
guidance, submit written or electronic comments on the draft guidance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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information, Center for Drug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]
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