Contemporary Approaches to Development and Manufacturing of Lyophilized Parenterals

Abstract

This chapter provides a historical reference, covers the progression in the scientific and technological development, highlights the contemporary aspects, and describes the application of the current USFDA guidance to the development through commercial life cycle for lyophilized products. Considerations of designing formulations, including the use of organic solvents, and influence of packaging are noted. Emphasis is placed on the engineering of the lyophilization process, estab- lishing the critical process parameters, and defining of the critical quality attributes. Utility of applying the US FDA process analytical technology initiative, as well as the notion of applying design space principles to the lyophilization process is included, leading into discussions on applying the current USFDA guideline on process validation to the development and manufacturing. Current challenges and unique aspects in development of lyophilized products are also highlighted, includ- ing poorly soluble drug substances, novel delivery systems, improving manufactur- ing capabilities, and reducing unit costs for world wide product distribution. This presentation encompasses the progression of the technological developments, reviews current thinking on the science and technology, and highlights contempo- rary approaches to the development and manufacturing of lyophilized parenterals.