02-21263. Draft Guidance for Industry on Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled “Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation.” This guidance provides recommendations to applicants on the chemistry, manufacturing, and controls (CMC); human pharmacokinetics and bioavailability; and labeling documentation for liposome drug products submitted in new drug applications (NDAs).

DATES:

Submit written or electronic comments on the draft guidance by November 19, 2002. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of the draft guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the draft guidance to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/​dockets/​ecomments. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

Liang Zhou, Center for Drug Evaluation and Research (HFD-180), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-7471.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation.”

Liposome drug products are defined as drug products containing drug substances (active pharmaceutical ingredients) encapsulated in liposomes. A liposome is a microvesicle composed of a bilayer of lipid amphipathic molecules enclosing an aqueous compartment. Liposome drug products are formed when a liposome is used to encapsulate a drug substance within the lipid bilayer or in the interior aqueous space of the liposome. A drug substance in a liposome formulation is intended to exhibit a different pharmacokinetic and/or tissue distribution (PK/TD) profile from the same drug substance (or active moiety) in a nonliposomal formulation given by the same route of administration. The complete characterization of the PK/TD profile of a new liposome drug product is essential to establish the safe and effective dosing regimen of the product.

The guidance provides recommendations to applicants on the CMC, human pharmacokinetics and bioavailability, and labeling documentation for liposome drug products submitted in NDAs. The guidance does not provide recommendations on: (1) Clinical efficacy and safety studies, (2) nonclinical pharmacology and/or toxicology studies, (3) bioequivalence studies or those to document sameness, (4) liposomal formulations of vaccine adjuvants or biologics, or (5) drug-lipid complexes.

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 agency's current thinking on liposome drug products: CMC, human pharmacokinetics and bioavailability, and labeling documentation. 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 requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit to the Dockets Management Branch (see ADDRESSES) written or electronic comments on the draft guidance. Two copies of mailed comments are to be submitted, except that individuals may submit one copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The draft guidance and received comments are available for public examination in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/​cder/​guidance/​index.htm or http://www.fda.gov/​ohrms/​dockets/​default.htm.

Dated: August 13, 2002.

William K. Hubbard,

Senior Associate Commissioner for Policy, Planning, and Legislation.