ABSTRACT
In the recent years, regulatory guidance has evolved to adopt a risk-based approach towards pharmaceutical manufacturing, which emphasizes that quality should be built into a process by design, leveraging development and manufacturing experience. The process validation guidance aligns activities with a product lifecycle concept occurring over three different stages of process design, process qualification, and continued process verification. This chapter discusses the application of scale-down models throughout the product life cycle to enable the design of robust processes and ensure safety, efficacy, and consistent product quality during commercial manufacturing. The key unit operations for both mammalian and microbial processes are discussed along with the general scale-down principles and parameters for each stage. Additionally, several case studies and examples are provided to demonstrate the development and application of scale-down models through the course of process development, validation, and commercial manufacturing.
