A review of chromatography methods for the large scale downstream protein purification of monoclonal antibodies /

Abstract

Researchers have continually proposed new non-chromatographic methods for manufacturing biopharmaceutical products. However, this report will show that chromatography remains the backbone of the downstream operation. Establishing a robust chromatographic manufacturing platform is a critical element that manufacturers of monoclonal antibodies (mAbs) must consider, covering activities from small scale to commercial processing. This report reviews a variety of methods utilised as part of the purification process within downstream biopharmaceutical processing of largescale commercial biologics. A protein’s properties such as its composition, molecular size, shape, charge or hydrophobicity will determine the modes of chromatography applied to optimise the purification process. Chromatography steps tend to be specific to a protein or type of proteins. Typically, the downstream process will have multiple chromatography steps which require large columns to be pre-packed with resins that must pass an evaluation prior to use. In industry, the traditional practice of packing resin into columns has widely been replaced and this report will look at current trends. The different media / resin that are packed into the column will dictate the type of chromatography. Major advancements in resin matrix and ligand chemistry has benefited the industry in the choices of Chromatography, including but not limited to Affinity Chromatography (AC), Ion Exchange Chromatography (IEC), and Hydrophobic Interaction Chromatography (HIC) and Mixed Mode Chromatography (MMC). Traditionally, downstream manufacturing is a batch process, and this report will examine advancements with significant interest in continuous processing due to the high costs associated with certain resins, particularity protein A resin. It is no surprise that large scale chromatography is targeted for developments in relation to new platforms and innovative, more efficient approaches. Evidence will be discussed on the impact new single use technologies and continuous chromatography is making and changing to change the way some manufacturers deliver important medicines to patients.