Model‐Based Preparative Chromatography Process Development in the QbD Paradigm

Preparative chromatography for separation of proteins and peptides continues to be the primary workhorse in purification of biopharmaceuticals. However, with the biotech industry moving to implement the expectations underlined in the recent regulatory initiative of quality by design (QbD), interesting and outspread applications of modeling tools for commercial process development and manufacture have emerged. The primary focus of biopharmaceuticals is the patient, and the patient needs are defined through the quality target product profile (QTPP), which in turn is affected by chemistry, manufacturing, and controls (CMC) activities. Fulfilling patients’ needs places some requirements on the product, and these elements are obtained through linkage of the QTPP to the list of critical quality attributes (CQAs). The chapter presents a figure that shows the effect of the feed concentration of a biopharmaceutical on the content of high molecular weight proteins (HMWP), a typical CQA in the drug substance addressed by purification.