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24th June 2019

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Use of Scale-down Techniques to Enhance the Recovery of Intracellular Enzymes

Author: Davy Rowan, KTP Associate

Davy-posterAs mentioned in my previous blogs (Meet Davy Rowan and Getting to Grips with Ultra Scale-down Techniques), implementation of ultra scale-down techniques has enabled extensive experimentation, especially of the flocculation step thus far. Due to the ability to undertake these studies in a cost-effective manner, we were able to look at several different enzymes and multiple sets of conditions. Using these techniques and methodology, an improved flocculation chemistry and method has been identified. This involves utilising a flocculating agent alongside a modulating agent, which allows the flocculant to precipitate most impurities whilst keeping our enzyme of interest in solution and producing a supernatant that is well clarified. Most importantly the chemistry used is food grade, kosher, halal and compatible with the requirements of our pharmaceutical customers.

These flocculation conditions have now been implemented as a process change across projects leading to more efficient operation. Our work has resulted in an increased recovery across this downstream processing step by between 10 and 300% dependent on the enzyme applied to. The 300% was for an enzyme development project which would not have been taken further in that configuration otherwise. It has also resulted in an increased overall recovery at process scale by 50% for a specific customer process, meaning fewer fermentations required to achieve the desired product quantity and significant financial savings for our customer. We are working closely with UCL to fabricate an ultra scale-down flocculation vessel to further improve our flocculation preparation and understanding – demonstrating our commitment to continuous improvement. This vessel is specifically designed to mimic the geometry and conditions of our larger process vessel to increase our reproducibility across scales.

I recently attended the BioProNET 6th Annual Science Meeting where I presented some of these findings in poster form. I received interesting insight from industrial and academic experts around this, stimulating new ideas for us to explore. Based on these insights, and learnings achieved at the UCL Design of Experiments for Bioprocess Optimisation MBI industrial course I recently attended, going forward we will be implementing design of experiments principles to explore this design space more fully and achieve an optimal and safe operating region in a more efficient and holistic manner.

Click here to download the poster on the use of scale-down techniques to enhance the recovery of intracellular enzymes.

Discussions with UCL and Biocatalysts Ltd experts have also led to the development of an experimental outline aimed at increasing our step yield around centrifugation at large scale. This involves drastically changing the way we operate; we have performed initial tests and achieved operator approval and buy in for the next stage, which we look forward to and anticipate achieving an increased step yield of over 10% if it goes well. This has been a great exercise of problem solving and communication across all levels of the company and the university, that has only been successful until now due to the excellent collaboration and cooperation across each. It has also stimulated discussion around how our centrifuge will operate at larger scale – in our extension, we are looking to ensure we will have the option of operating in this configuration to maximise our yields.

Check back in soon to find out how the design of experiments and centrifugation testing is progressing.

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