Chromatographic Scale‐Up on a Volume Basis

The topic of scale-up for chromatographic process steps can be divided into two main areas: scale independent, and scale dependent. This chapter deals with the principle of scale-up from the laboratory to a pilot facility and into production. The scale-up of a chromatographic separation is in principle a simple procedure since the process parameters are scalable in a linear fashion. The chapter presents more than 10 years of experience in chromatographic scale-up on a volume basis. It includes the theoretical background and proof of concept as well as industrial cases with large-scaling factors. Examples include ion exchange chromatography (IEX), reversed-phase chromatography (RPC) and hydrophobic interaction chromatography (HIC) processes for the separation of both peptides and large proteins. The chapter presents applications of the scale-up concept in actual production cases including basic scale-up, optimization, and actual process design of multiple steps.