In April 2018 the FDA has released the final guidance for pharmaceutical industry on liposome drug products. The new guidance incorporates the finalized recommendations on liposome drug products manufacturing and includes the following main chapters: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics: Bioavailability and Bioequivalence; and Labeling.
According to the definition given in the guidance “Liposomes are vesicles composed of a bilayer (uni-lamellar) and/or a concentric series of multiple bilayers (multi-lamellar) 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 generally contained in liposomes.”
There may be parenteral, oral and topical routes of administration of liposome drugs. For injectable liposome medications, it is necessary to prove that the drug is sterile and that it does not contain pyrogens or bacterial endotoxins.
The new guidance is based on the Quality by Design (QbD) principles according to ICH Q8(R2) Pharmaceutical Development. It means that it includes the control of critical variables (Critical Quality Attributes [CQAs] are chemical, physical, biological and microbiological attributes that can be defined, measured, and continually monitored to ensure final product outputs remain within acceptable quality limits) and establishment of a Design Space. It is also recommended to include a detailed process flow diagram as well as the description of unit operations with specifying process parameters and process controls documentation. The ranges of process parameters must be proved by pharmaceutical development investigations. Liposomes are very sensitive to any alterations in the conditions of production as well as changes in scale (batch sizes). Therefore, it is necessary to ensure a proper control of product development and manufacturing process. The manufacturing process parameters that may influence the quality of liposome drug products are а shear force, pressure, pH, temperature, batch-size-related hold times, lyophilization parameters, etc.
It is expected that implementation of new guidance allows to define more specific requirements for the manufacturing and quality control of liposome products and facilitates a more standardized electronic registration dossier (that will hopefully result in fewer questions from the regulatory bodies) for these products.