ABSTRACT
This chapter focuses on the International Conference on Harmonization (ICH) Q5C stability guideline on biologicals. It outlines chemistry, manufacturing, and controls (CMC) requirements for biological products. The chapter discusses requirements for manufacturing process validation and quality control/assurance, including the concept of quality by design in Biologics License Application (BLA) submissions. The CMC requirements for biosimilars in the European Union are those described in the ICH Common Technical Document (CTD) Quality Module 3 with supplemental information demonstrating comparability or similarity on quality attributes to the reference medicine product. A typical BLA includes form Food and Drug Administration 356h, applicant information, product/manufacturing information, pre-clinical studies, clinical studies, and labeling. The United States suggests submission following CTD format for drug substance, which consists of general information, manufacture, characterization, control, reference standards, container closure system, and stability. The goals for fermentation are to increase the expression level of a deficiency without compromising the correct amino acid sequence and post-translational modification.
