ABSTRACT
Researchers in discovery organizations tend to select drug candidates based on biological properties, for example, in the case of antibodies, based on binding afnity, potency, efcacy, cross-reactivity with target of species for toxicological studies, and epitope. However, to develop a candidate into a drug, additional properties, such as expression and purication yields, aggregation propensity, stability, viscosity, physicochemical prole, compatibility with in vivo environment, and immunogenicity, need to be assessed. Departments or contract research organizations responsible for developing a process to manufacture a safe biologic drug of high quality in a costefcient, reproducible way are interested in these additional properties of the drug. Consequently, selection of the best molecule, taking both biology and developability into consideration, is a crucial step for successful development of biologic drugs (Figure 7.1). Developability addresses risk assessment and risk mitigation to improve the likelihood that selected biologic drug candidates can be successfully developed into medicines available to patients. Since major process factors are investigated during the developability assessment, an additional output of the assessment is a judgment on whether or not a drug candidate can be manufactured with a platform process. In the context of this chapter, the term developability assessment of a biologic drug candidate is understood as experimental, not computational, investigation to assess manufacturing feasibility (productivity, stability, process), ease of formulation for a specic route of administration, and importantly, compatibility with in vivo conditions (termed in vivo tness in this chapter), such as cross-reactivity, half-life, stability in the in vivo environment, and immunogenicity. In short, during developability assessment, drug candidates are selected or, if necessary, engineered to fulll manufacturing, formulation, and safety characteristics before expensive development efforts are initiated. The approach denes best candidates with respect to manufacturing, formulation, and safety, in contrast to adapting manufacturing processes to enable preparation of a difcult-to-produce drug. Adaptation of processes to prepare high-quality biologic drugs at later development stages becomes increasingly costly. In silico identication of potential post-translational modication (PTM) sites
known to possibly impact protein integrity, and determination of the isoelectric point (pI) are the only computational components of this chapter.
