ABSTRACT
This chapter focuses on quality aspects that can be directly measured on process and product to assure efficacy, safety and stability of the product physicochemical profile. The first case study of a Quality-by-Design-based biopharmaceutical development focused on the manufacturing process of a-Mab, a humanized IgG1 antibody used in the treatment of indolent non-Hodgkin's lymphoma in adults. As will be further explored in the next section, multidimensional spaces result in a more flexible operation, since the regulatory agencies allow the movement within an approved Design Space without the need for Chemical Manufacturing Control preapproval. Given that ICH Guideline Q8(R2) incentivizes dimensionless process Design Space validation, it is advantageous for the manufacturer to develop more sophisticated mechanistic models that explain the connections between process parameters and critical quality attributes. Process validation in bioreactors comes after the setup of input parameters to obtain the desired outputs.
