Current Developments and Future Directions of Downstream processing

Downstream processing of high-value biological products has long been dominated by adsorptive packed bed chromatographic approaches, despite a number of limitations to this technique, including the high cost, low throughput and complexity of scale-up. However, the ability of currently available expression technologies to produce ever higher yields and concentrations of high-value biological products means that the downstream bioprocessing community has begun to consider alternatives to this traditional approach that may at least reduce the extent of its use. Many consider that the traditional approach of small incremental improvements to operations already working at the limit is proving ineffective at resolving downstream processing bottlenecks.
Consequently, there is a drive to investigate unit operations that might replace some of the current dependence on packed bed chromatography. Recent reviews suggest that the most notable trends in this area are to integrate steps (thereby reducing the number), the development of platform technologies (so as to move towards a more systemic approach), further process optimisation and the increased use of disposable equipment.
Process integration is a logical approach towards reducing costs as a reduced number of steps will allow greater throughput and potentially yield. This approach has already delivered a number of new technologies, including affinity precipitation and expanded bed adsorption.
Unsurprisingly, the focus tends towards eliminating intermediate purification steps and moving directly from product capture to product polishing. The aim is to develop an integrated process which uses the minimum number of steps in a logical way, with each step focusing on the removal of a certain impurity. This has resulted in some polishing steps being employed before bulk separation processes, for instance, the removal of specific proteases early on in the process to preserve product stability. However, to implement such a concept, a systematic approach has to be taken towards process development. Increased regulatory issues, and the fact that integrating new developments into the process can often yield haphazard results, have necessitated that a more organised approach be taken. This must be undertaken to ensure that individual steps during downstream processing all work together and are managed in such a way that optimum processing is achieved at each step. A current lack of systematic approaches highlights the need to design platform technologies for specific types or classes of biological products so as to make process optimisation a simpler task. This will be aided by developments in microscale bioprocess optimisation and process simulation software, which have allowed the formulation of a process very early in the development of a product.Finally, the trend towards disposable technology is likely to continue in the foreseeable future and any novel developments in downstream processing must be able to incorporate such a move. For example, recent studies have shown that smaller disposable membranes use up to 95% less buffer than conventional systems and can reduce monoclonal antibody polishing costs by 70%. Disposables are also encroaching upon upstream bioprocessing with disposable bioreactors as large as 1000 L being developed. All of these areas and approaches, particularly systematic approaches, are likely to play key roles in future developments for optimising downstream processing of high-value biological products.

مواضيع ذات صلة

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