Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

Abstract

The article examines how a small set of easily implemented micro biochemical engineering procedures combined with regime analysis and bioprocess models can be used to predict industrial scale performance of biopharmaceutical protein downstream processing. This approach has been worked on in many of our studies of individual operations over the last 10 years and allows preliminary evaluation to be conducted much earlier in the development pathway because of lower costs. It then permits the later large scale trials to be more highly focused. This means that the risk of delays during bioprocess development and of product launch are reduced. Here we draw the outcomes of this research together and illustrate its use in a set of typical operations; cell rupture, centrifugation, filtration, precipitation, expanded bed adsorption, chromatography and for common sources, E. coli, two yeasts and mammalian cells (GS-NSO). The general approach to establishing this method for other operations is summarized and new developments outlined. The technique is placed against the background of the scale-down methods that preceded it and complementary ones that are being examined in parallel. The article concludes with a discussion of the advantages and limitations of the micro biochemical engineering approach versus other methods.

Intelligent Automation Platform for Bioprocess Development

“…A large number of researches focus on the high throughput screening (HTS) which is an essential part of drug discovery and development (Gribbon & Andreas 2005;Mishra et al 2008). Many studies have contributed to microbial fermentation (Kostov et al 2001;Rios-Solis et al 2013 (Saitoh & Yoshimori 2008), precipitation (Knevelman et al 2010;Titchener-Hooker et al 2008) and chromatography (Chhatre et al 2010;Wiendahl et al 2008). …”

Hydrodynamic Considerations in Bioreactor Selection and Design

“…For example, protein producing microorganisms, which are often used in pharmacokinetics, produce a mixture over time that is damaging to the bacteria aside from the surface active agent properties of the protein. Shear is tolerated by the microorganisms in this mixture, but air-liquid interfaces, which are naturally very common in gas-liquid processes, can lead to denaturation [28].…”

“…For example, it is common in the biopharmaceutical industry to start the design phase once approval of a drug has been secured; however, the design process requires a significant amount of time during which the patent clock is ticking. Hence, costly delays are very common [28].…”

Anchoring high-throughput screening methods to scale-up bioproduction of siderophores

“…Both screening of production conditions (including selection of strains and medium composition) and downstream processes can be assessed within these reactors [7,8]. In this case, sub-optimal conditions of heat and mass transfer, in particular oxygen transfer, must be avoided by using proper engineering strategies [9].…”

“…The former method enables high production volumes at relatively low cost as it is based on economyof-mass manufacturing while the latter is economy-of-scale based [10]. The study of the limiting steps will allow the full understanding of the economic viability of the process [8].…”