2010-6171. Revised Draft Guidance for Industry on Pharmacokinetics in Patients With Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing and Labeling; Availability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.

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The Food and Drug Administration (FDA) is announcing the availability of a revised draft guidance for industry entitled “Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing and Labeling.” The draft guidance is intended to assist sponsors planning to conduct studies to assess the influence of renal impairment on the pharmacokinetics of an investigational drug.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comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit written or electronic comments on the draft guidance by May 21, 2010.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Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201,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FDA is announcing the availability of a revised draft guidance entitled “Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing and Labeling.”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 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.