Guideline for the Development of Liposome Drug Products

3.1 Description and composition ....................................................................................... 4 3.2 Formulation development and characterization ........................................................... 4 3.2.1 Pharmaceutical development ............................................................................... 4 3.2.2 Characterization of drug products ........................................................................ 5 3.2.3 In vitro release test ............................................................................................... 8 3.3 Manufacturing process and process controls of liposome drug products .................... 8 3.3.1 Process of formation of liposomes ....................................................................... 9 3.3.2 Encapsulation process of the active substance in liposomes ............................... 9 3.3.3 Sizing process ...................................................................................................... 9 3.3.4 Process for surface modification such as PEGylation ........................................ 10 3.3.5 Sterilization process ........................................................................................... 10 3.4 Control of liposome components ............................................................................... 10 3.4.1 Quality attributes ................................................................................................ 10 3.4.2 Manufacturing process and process control ....................................................... 11 3.4.3 Specifications ..................................................................................................... 11 3.4.4 Stability .............................................................................................................. 12 3.5 Control of liposome drug products ............................................................................ 12 3.5.1 Specifications ..................................................................................................... 12 3.5.2 Identification ...................................................................................................... 12 3.5.3 Endotoxin test .................................................................................................... 12 3.5.4 Biological assay ................................................................................................. 13 3.6 Stability ...................................................................................................................... 13 3.7 Changes in the manufacturing ................................................................................... 14