The new contract will establish a suspension-based manufacturing platform and allow for the production of a variety of viral vectors for gene therapies and viral vector-based vaccines.
Exothera recently announced a significant expansion of its manufacturing capabilities, with two new GMP facilities built at the company’s Jumet site near Brussels, Belgium. Those sites, which include a variety of functions from research and development to commercial production, are set to begin GMP production this summer.
When asked to expand on what will be delivered under this contract, Clive Glover, general manager, gene therapy at Pall, told BioPharma-Reporter that the company will provide a full end-to-end solution to Exothera including stirred tank bioreactors and filtration and chromatography equipment and all the mixers and totes required to manufacture viral vectors at large scale.
Benefits of bioreactors
How does a suspension-based manufacturing platform allow for the production of a variety of viral vectors for gene therapies and viral vector-based vaccines?
“Viral vector production primarily relies on the use of HEK293 mammalian cells to produce the virus. Traditionally, HEK293 cells are adherent and this can restrict the scale to which production can take place because of the challenges of scaling adherent-based processes in standard tissue culture flasks.
“As the demand for large scale viral vector production increases, manufacturers have been addressing these scaling challenges by turning to bioreactors.
“Fixed bed bioreactors, such as the iCELLis 500, can be used to scale up production of adherent HEK293 cells and this has been used successfully for commercial gene therapies. Alternatively, it is possible to adapt HEK293 cells to grow in suspension mode and this allows the cells to then be cultured to large scale in stirred tank bioreactors such as the Pall Allegro STR,” said the gene therapy specialist.
And he said Pall’s STR bioreactors could be adapted, if needed, to the perfusion mode, allowing higher growth and density of cells.
“With minimal modifications, the Allegro STR Bioreactors at 50 L and 200 L scales have variants available where modifications to the bioreactors allow for a perfusion process to be conducted, in addition to the traditional batch and fed-batch modes to support GT suspension perfusion applications.
“Growing cells in perfusion mode allows them to reach high cell density and will likely increase the overall yield from the culture,” said Glover.
Key learnings
What key learnings can Pall share from working with many of the industry leaders to develop scalable upstream and downstream processes that may benefit’s Exothera’s production?
“The requirement for large scale viral vector production is relatively new and hence the processes required to do this are still very much in development. At Pall, within our Accelerator Process Development Services, we have developed more than 30 different large scale viral vector processes over the last few years on a variety of different viral vector types and at several different scales.
“There are particular challenges associated with all unit operations. We have developed particular expertise in optimizing the transfection process both in adherent and suspension. We have also worked considerably on optimizing the downstream purification steps.”
