The US Food and Drug Administration (FDA) has issued revised draft guidance, Liposome Drug Products Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation to discuss what types of information an applicant, should submit in its new drug application (NDA), abbreviated new drug application (ANDA), or biologics license application (BLA) for a liposome drug product reviewed by FDA's Center for Drug Evaluation and Research.
The discussion addresses the following topics for liposome drug products: chemistry, manufacturing, and controls (CMC); (B) human pharmacokinetics and bioavailability or, in the case of an ANDA, bioequivalence; and labeling in NDAs and ANDAs. It replaces the draft guidance for industry on Liposome Drug Products, Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation that that was published in August 2002.
Liposomes are microvesicles composed of a bilayer and/or a concentric series of multiple bilayers separated by aqueous compartments formed by amphipathic molecules such as phospholipids that enclose a central aqueous compartment. In a liposome drug product, the drug substance is contained in liposomes.4 52 Typically, water soluble drugs are contained in the aqueous compartment(s) and hydrophobic drugs are contained in the lipid layer(s) of the liposomes. Release of drugs from liposome formulations can be modified by the presence of polyethylene glycol and/or cholesterol or other potential additives in the liposome. A liposome drug formulation is different from (1) an emulsion, which is a dispersed system of oil in water, or water in oil phases containing one or more surfactants, (2) a microemulsion, which is a thermodynamically stable one phase system containing oil or lipid, water and surfactants, and (3) a drug-lipid complex.
The recommendations in the revised draft guidance focus on the unique technical aspects of liposome drug products. The guidance does not provide recommendations on clinical efficacy and safety studies; nonclinical pharmacology/toxicology studies; or drug-lipid complexes.
Source: US Food and Drug Administration