On April 4, 2018, FDA issued final guidance on Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation. This guidance explains the type of information that applicants should submit for NDAs or ANDAs for liposome drug products to the Center for Drug Evaluation and Research (CDER). Many of the principles in the guidance also apply to liposome drug products to be marketed under BLAs.
Liposomes are vesicles composed of at least one lipid bilayer formed by molecules that have both hydrophilic and hydrophobic parts (such as phospholipids) that surround an aqueous core. A liposome drug product uses the liposome as a vehicle to transport a drug substance contained either in the aqueous core, if it is a water soluble drug, or contained in the lipid bilayer(s), if it is a hydrophobic drug.
The guidance outlines that NDAs and ANDAs should list the name and composition of all drug product components, the amount and molar ratio of each lipid component, and the amount of the drug substance. The application should include the physiochemical properties of each lipid component, such as the drug encapsulation efficiency and liposome drug loading. FDA recommends including the manufacturing process for the drug product as well as the lipid components, including different information for a lipid that is synthetic, semi-synthetic, or naturally sourced. The application should also include results from stability studies for the drug product as well as the lipid components.
Regarding bioavailability studies, FDA recommends NDA applicants consult the appropriate CDER review division for advice on determining bioavailability because of the unique drug release properties of liposome drug products. Regarding pharmacology studies, FDA recommends conducting comparative studies between the liposome drug formulation and nonliposome drug formulation, where one has been approved, to compare differences in absorption, distribution, metabolism, and excretion (ADME).
Finally, regarding labeling, FDA recommends labeling the product with a caution that products with the same active ingredient may behave differently in a liposome drug product than a nonliposome drug product..