Bioseparation: The limiting step in bioprocess development

Abstract

Editorial Bioseparation: The limiting step in bioprocess developmentBioseparation can be defined as the set of sequential unit operations which, in a bioprocess, result in the recovery and purification of biological products -including proteins, enzymes, vaccines, colorants or antibodies. These are usually commercialized according to their biological function, and it is easy to anticipate that the bioseparation processes required to obtain, for example, industrial enzymes and oral or injected delivery products will differ greatly. It has been generally recognized that the recovery and purification stages (i.e. bioseparation), because the purity needed varies, represent the limiting steps in process development -but despite recent investigations, in particular from the industry, extensive research in this area has generally been neglected. Although several explanations for this trend can be given, we would like to highlight three major factors: (i) historical effect, (ii) process complexity and (iii) regulatory and validation issues. The historical effect is attributed to the need to develop the production stage of bioprocesses first. Thus, the bioprocesses initially developed to bring biological products to the market were strongly oriented towards the optimization of the fermentation step -neglecting the bioseparation part. This tendency was further accentuated by process complexity issues as fermentation, representing only one unit operation in comparison with typically more than ten unit operations for the bioseparation part of the process, was more thoroughly investigated. Finally, it is well-known that the implementation of advances in bioseparation processes has been hindered by validation and cost constraints. Regulatory and validation considerations have promoted a reluctance to embrace an entirely new technology, in this and other fields of biochemical engineering and biotechnology.In this Special Issue, JCTB presents a particular approach to trends and challenges in bioseparation. We have collected a Mini-Review, a Perspective, three Reviews and seven original research papers to outline the evolution of the type of problems, as well as the technologies, encountered in the field of product recovery and purification.The past, present and future challenges in efficient separations of recombinant proteins are nicely addressed by Juan Asenjo and Barbara Andrews in the first Mini-Review 1 . It raises how the challenges faced by bioseparation have changed over the past few years. The three main issues addressed are the increase in product concentration, the change of paradigm regarding the use of protein A approach and the need for complex and sophisticated mathematical models -key issue that will require particular attention from both academics and industrialists. The future application and industrial implementation of in-situ product removal (ISPR) techniques are addressed in the Perspective by John Woodley and co-workers 2 . The findings reported there are the results of a round-table discussion held at the...

Extraction and Purification of Bioproducts and Nanoparticles using Aqueous Two‐Phase Systems Strategies

“…It has been generally recognized that because the purity requirements vary, the recovery and purification, i.e., bioseparation of bioproducts, represents the limiting steps in process development [58]. The biotechnology industry faces challenges and trends in bioseparation today that are different from those that existed a decade ago.…”

Fractal morphology of Beta vulgaris L. cell suspension culture permeabilized with Triton X-100®

“…It has numerous advantages, including more homogeneity and efficiency than traditional technologies for chemical, pharmaceutical and other commercial products. Product recovery is of crucial importance as downstream processing often accounts for 50 to 90% of the production costs (Rito-Palomares, 2008). Since many secondary metabolites are stored in vacuoles, it is necessary to improve the excretion of these substances into the culture medium, using a non-lethal method.…”

Aqueous Two‐Phase Systems at Large Scale: Challenges and Opportunities

“…Although this is not the best optimization technique it has a widespread use for ATPS optimization. This strategy has been used to obtain improved system recovery and purity for several products, for example; invertase, uricase, and in the same study for pseudo‐viral particles, B‐phycoerythrin, C‐phycocyanin, and lutein …”

“…This strategy has been used to obtain improved system recovery and purity for several products, for example; invertase, [33,34] uricase, [35] and in the same study for pseudo-viral particles, B-phycoerythrin, C-phycocyanin, and lutein. [36]…”