Design strategies for integrated protein purification processes: challenges, progress and outlook

Abstract

The key to successful and efficient protein purification is the selection of the most appropriate purification techniques and their combination in a logical way to obtain the desired purification in the minimum number of steps. However, the rationalization of protein purification process development is faced with a number of challenges. In this paper, the challenges in protein purification process development are captured. The state-ofthe-art in protein purification process synthesis and design is reviewed and the strengths and weaknesses of the current strategies highlighted. Finally, views on the future directions of protein purification process development are presented.

A perspective on process synthesis: Challenges and prospects

“…With advances in directed evolution techniques (Johannes and Zhao, 2006) and the growth of the biopharmaceutical sector (Nfor et al, 2008), the process synthesis of recovery and purification of the bioproducts and proteins that are produced by cell cultures is becoming an important problem to manage their overall production cost. These mixtures are considerably different compared to the downstream feeds of traditional chemical process industry: (1) the desired product concentration is generally very low and there may be a host of compounds with very similar physical and chemical characteristics to the desired product, (2) the mixtures may contain hundreds of compounds with little or no thermodynamic or kinetic data, and (3) the desired products and the other compounds in the mixture are easily degradable (Malwade et al, 2012).…”

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

“…The excellent selectivity properties and relatively mild conditions in liquid chromatography have made it indispensable in the downstream process development of therapeutic proteins for which very high purity of the active product is paramount and the time-to-market short [1,2]. While the vast majority of chromatographic media used for protein purification today are designed to operate in single interaction mode such as size exclusion, electrostatic interaction, hydrophobic interaction and bioaffinity interaction [3], multimodal or mixed mode chromatographic media, on the other hand, are intentionally functionalized with ligands capable of two or more orthogonal modes of interactions to effect the separation.…”

Production Rate‐Dependent Key Performance Indicators for a Systematic Design of Biochemical Downstream Processes

“…Design approaches available for bioprocess development are typically classified into knowledge-based approaches like rulesof-thumbs [3,4] and expert systems [5,6], model-based approaches like optimization [7,8] and superstructures [9], and experimental approaches like design of experiments [10] and high-throughput screening [11,12]. A comprehensive overview of these design approaches is given by Nfor et al [13].…”