Liquid–liquid extraction of biopharmaceuticals from fermented broth: trends and future prospects

Abstract

Biopharmaceuticals are one of the most important groups of biotechnological products, representing one-quarter of all pharmaceutical sales and providing suitable and efficient medical care for many previously untreatable diseases. However, their production and purification usually require complex processes, resulting in extremely expensive final products. Thus, the development of newer, simpler and cheaper methods for biosynthesis and purification of these biocompounds, as well as proper integration between these stages, are crucial to reduce their commercial costs and to increase the scale of biopharmaceuticals' medical use. One solution for this concern relies on the proper integration between upstream and downstream processing applying liquid-liquid extraction systems as an intermediate stage. Recently, several works reported that a proper choice of liquid-liquid systems such as aqueous biphasic systems (ABS) can be a suitable platform to simplify, reduce the number of the downstream stages, improve the recovery and purification yields and, consequently, decrease biopharmaceuticals' manufacturing costs. This review will explain the general concept of biopharmaceuticals, their main production and purification methods, particularly, exploring the use of ABS as effective and integrative platforms for their recovery and purification, and providing further insights into the future trends and prospects in the field.

Controlling the l‐asparaginase extraction and purification by the appropriate selection of polymer/salt‐based aqueous biphasic systems

“…In this context, due to their high water content, aqueous biphasic systems (ABS) have been studied as biocompatible and environmentally friendly alternatives for the recovery and purification of different bioproducts, particularly the ABS using: (i) inert, biocompatible and biodegradable polymers, such as polyethylene glycol (PEG) and polypropylene glycol (PPG); (ii) buffers that simulate the cellular environment; and (iii) biocompatible salts derived from renewable sources with lower toxicity and costs, such as cholinium‐based‐salts . Moreover, the application of these systems and solvents obey the principles of Green Chemistry and the concerns of biocompatibility and selectivity needed on the downstream processing of biopharmaceuticals …”

“…11 Moreover, the application of these systems and solvents obey the principles of Green Chemistry 12 and the concerns of biocompatibility and selectivity needed on the downstream processing of biopharmaceuticals. 13 ABS can be used as an initial (low resolution) downstream stage by reducing contaminants and sample volume, and consequently the complexity and cost of further biopharmaceutical purification steps. 14 As an example, these systems were successfully used on fractionation of biomolecules like proteins and carotenoids by separating them according to their intrinsic properties, namely the solubility, ionic strength, molecular mass, polarity and surface charge.…”

Purification of monoclonal antibodies in a stirred cell with polyethyleneimine‐modified polyethersulfone ultrafiltration membrane

“…Hence there is significant interest in alternatives that decrease the number of processing steps without the loss of purity of the final product. Some of those alternatives are aqueous two‐phase extraction, precipitation and fractionation by membrane ultrafiltration …”

Improving the cost effectiveness of enhanced green fluorescent protein production using recombinant Escherichia coli BL21 (DE3): Decreasing the expression inducer concentration

“…Additionally, even though lactose has some advantages over IPTG (particularly lower costs and toxicity), it can generate unwanted autoinduction . On the other hand, induction by changing processual conditions are usually considered more economically attractive than chemical induction using IPTG or lactose; however, the stress can cause several unwanted responses, as for example: heat‐shock; concomitant upregulation of proteases ; degradation of the target protein; increase of the fermented contaminants, and consequently, the complexity of downstream processing (the most expensive stages of protein manufacturing budget ). Therefore, a proper balance between cost and benefit regarding the choice of inducer (chemical or processual) is of upmost importance.…”