The project sought to validate the use of ChemStress technology as an analytical tool in selecting the host cell to be used in the manufacturing of biologic drugs. This was successfully achieved in the BIOSIM project following validation at seven industry sites with all Deliverables successfully completed.
The manufacturing of the ChemStress plates was outsourced following EU procurement guidelines. Detailed Final Plate Specification (D2.1) was achieved and plates were produced achieving the targeted manufacturing cost (D2.2). These plates were then used in a series on industry validation studies (D3.1). The industry partners who participated in the project include; GSK Stevenage UK, Fujifilm Diosynth Billingham UK, GE Healthcare Upsalla SWEDEN, Alexion Pharma NewHaven USA, Canadian National Research Council Montreal CANADA, Allergan Pharma Liverpool UK, Pfizer Penzberg GERMANY, Danish Technological University Copenhagen DENMARK.
Based on the experience of working with industry staff a End User Working Protocol (Instruction For Use) was developed (D4.1). It also became clear that there was no necessity to develop an Enterprise version of the ValitaApp (D4.2) software as the standalone software used in the product was deemed adequate and better suited to local industry security requirements. Analysis and sharing of the results (D6.1) led to a number of changes in the preparation for the first ChemStress product launch. These included; modification of original shipping guidelines to require product to be shipped and stored at temperature between 2-8C following the Validation, Stability and Shipping testing (D5.1) product will not carry a CE Mark as it is Research Use Only (RUO) and therefore does not fall within CE applicability (D5.2). In place of a CE Mark a Product Quality File has been developed and submitted as a deliverable.
The original expectation of the BIOSIM project was that the ability of ChemStress technology to assess cell stability would be demonstrated by correlating ChemStress results against the existing measures used to determine stability. The results of the project proved that this was not possible as stability is currently determined based on simple product titre (amount of drug produced) not falling off by more than a fixed percentage. What ChemStress showed was that many cells that would be determined to be stable under current approach (product produced did not fall significantly) displayed exaggerated responses in terms of either growth or productivity. Large increases in productivity compensated for large fall off in growth and vice versa. These cells were not in fact stable and should not be brought further in development as they are more likely to fail in full scale up.
The results formed the basis of two Peer Review publications (D6.2) 14 oral presentations and 11 poster presentations at industry conferences. In addition results have been communicated in a Webinar (with industry partner) and on company website.
