Advances in Downstream Processing of Monoclonal Antibodies.

Although mAbs have great therapeutic potential, their use in medicine is currently limited by the high cost of their manufacturing. Significant developments in upstream processing technologies have caused downstream processing (DSP) to become the manufacturing cost-driver. DSP consists of a number of operations included in the capture, polishing, and formulation steps that contribute to excessive material and buffer consumption. This is particularly true for the capture and polishing steps, in which tedious and costly chromatographic operations are involved to ensure an adequate purity level of the medical product. The final formulation step also increases the burden of buffer consumption. This review focuses on those time- and material-consuming DSP operations and describes key issues and challenges related to their realization. In each of the steps, capture, polishing, and formulation, the platform processing approaches are presented as well as directions for their development. In addition, we present alternative nonchromatographic approaches that can potentially be used in the capture and polishing steps, such as precipitation or extraction. Furthermore, we describe mAb processing by crystallization, which can potentially serve as an alternative platform in both polishing and formulation steps.