Scientific and regulatory considerations for development and commercialization of poorly water-soluble drugs

Abstract

This chapter focuses on the Chemistry, Manufacturing, and Controls (CMC) from the scientific and regulatory perspective of the development of poorly water-soluble drugs to provide insights into regulatory filing from Investigational New Drug Application (IND) to New Drug Application (NDA) submission. The chapter includes two primary sections to cover the two regulatory stages for CMC module of filing, IND and NDA. The IND section of the chapter includes the following contents: (1) brief description of general filing requirements as outlined in the Code of Federal Regulations (CFR) and relevant guidances; (2) discussion of potential regulatory issues for developing poorly water-soluble drugs using various pharmaceutical technologies in the IND stage, i.e., solid-form selection, particle- size reduction, lipid formulation, and amorphous solid dispersion. The NDA section of the chapter includes the following: (1) general regulatory filing requirements of an NDA application; (2) potential regulatory issues associated with poorly water- soluble drugs; detailed discussions are carried out on topics including solid-form selection of the drug substance, drug product development using novel pharmaceutical technologies, development of control strategies, etc.; (3) case studies of marketed drug products of poorly water-soluble drugs in various dosage forms; this part uses the public information of the approved products as examples to support the discussions as outlined in part (2); and (4) brief discussion on the concept of Biopharmaceutics Classification System (BCS) in the development of poorly soluble drugs. The book chapter concludes with a brief summary which emphasizes on the link between regulation and science.