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Advanced Therapy Accelerator Tackles Continuous Manufacturing Challenges

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A UK organization supporting advanced therapy innovation is working to implement continuous upstream processing for Adeno-Associated Viruses (AAV). The Cell and Gene Therapy Catapult has developed systems for high cell density transfection and for continuous perfusion. The group is now working to bring the component parts together.

“We’ve assembled a platform for high density continuous harvest and shown some proof-of-concept data,” explains Molly Tregidgo, PhD a senior bioprocess scientist at the CGT Catapult. “Now we’ve brought the platform together, we’re focused on boosting the productivity of the production phase.”

Continuous processing is a well-known technique for monoclonal antibody (mAb) production, explains Tregidgo, but has only begun attracting interest in AAV production as manufacturers move towards producing more therapies for systemic disease.

Reduce biomanufacturing costs


“The cost of goods is a huge driver towards making manufacturing more cost effective and increasing product availability to patients,” continues Tregidgo.

As Tregidgo points out, continuous processing offers an opportunity to reduce manufacturing costs, but there are currently technical obstacles to its adoption in the upstream part of product manufacturing. For example, transfecting cells at high density can be challenging. Also, it’s hard to adopt the perfusion methods common in mAb production because AAVs tend to get stuck in the filters as the product is continuously removed from a bioreactor.

To address this challenge, the team at the CGT Catapult experimented with high cell density transfection in a 24 deep-well plate, using different combinations of reagents. By using Design of Experiment (DOE) approach, Tregidgo says they were able to avoid the limitations of using high concentrations of reagents and achieve a similar transfection efficiency with a high density of cells to using a standard process.

In addition, the team experimented with turning to a continuous harvest approach, adapted from mAb production, to manufacture an extracellularly produced AAV. When the AAV got stuck in the filter, Tregidgo and the team found an alternative filter in the academic literature that permitted 100% transmission of product across the membrane.

After two successful experiments, the team is now moving onto combining the transfection and continuous harvest steps. Other investigators at the CGT Catapult are also looking at continuous downstream processing of AAV.



The post Advanced Therapy Accelerator Tackles Continuous Manufacturing Challenges appeared first on GEN - Genetic Engineering and Biotechnology News.
 
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