” This draft version includes recommendations explicitly for liposome drug products submitted in new drug applications (NDAs). In detail, recommendations concerning the submission of a new liposomal product are given regarding physiochemical properties,
description of manufacturing process and process controls, and control of excipients and drug products. Control of excipients includes all parameters which are necessary to define lipid components, including description, characterization, manufacture, and stability. Control of drug products is dealing with the specifications. In principal, Inhibitors,research,lifescience,medical the recommendations of the ICH (International Conference on Harmonization) guideline Q6A “Specifications, Test Procedures and Acceptance criteria for New Drug Substances and New Drug Products: Chemical Substances” are appropriate, but additional testing Inhibitors,research,lifescience,medical is necessary. In particular, physicochemical parameters are critical for product quality for each batch. Furthermore, aspects are addressed such as assaying BAY 87-2243? encapsulated and nonencapsulated drug substance, lipid components, and degradation products, as well Inhibitors,research,lifescience,medical as in vitro tests for drug release from liposomes. The second
part of this document is dealing with human pharmacokinetics and bioavailability. In particular, requirements concerning the quality and potency of bioanalytical Inhibitors,research,lifescience,medical methods are discussed. Therefore, the recommendations are focused on the validation of these methods and the capability to distinguish between encapsulated and nonencapsulated drug substances. Similar recommendations are given for in vivo integrity and prompt delivery stability considerations, respectively. For safety assessment, validated in vitro assays are recommended to simulate the liposomal release and/or interaction with lipoproteins and other proteins in the blood. In an additional chapter, Inhibitors,research,lifescience,medical studies for pharmacokinetics and bioavailability are recommended, such as mass balance studies and pharmacokinetic studies. Finally, general recommendations concerning
the labeling requirements are given. This draft guidance does not provide recommendations on clinical efficacy and safety studies, nonclinical pharmacology and/or toxicology studies, bioequivalence studies or those to document the sameness, liposomal formulations Brefeldin_A of vaccine adjuvant or biologics, and drug-lipid complexes. Unfortunately, during the intensive discussion process no conclusion regarding the appropriate approaches to access pharmacokinetics and bioavailability was achieved. Hence, this document has only draft status to this date. In 2006, a reflection paper was published on nanotechnology-based medicinal products for human use reflecting the current thinking and the initiatives by EMA in view of recent developments in relation to this scope.