Efforts to use cell-based assays for testing all batches of biologics were held up by regulatory worries about the potential for viral contamination in production of coagulation factor VII. To ease the fears of European regulators Novo Nordisk has added a nanofilter to its production process.
“The filter actually removes the virus particles because the pores of the filter are so small that even particles as small as viruses are stopped”, Søren Kamstrup, team leader, protein separation and virology, said.
Adding the filter cuts the risk animal derived raw materials used in production will contaminate the finished product with viruses. By adding this layer of protection Novo Nordisk reassured regulators that a cell-based assay is sufficient for batch testing.
Mads Krogsgaard Thomsen, chief scientific officer at Novo Nordisk, said: “For production control…it’s completely obsolete in my mind. It’s just been a question of documenting that scientifically.” Animal tests in development “are still needed and will be needed into the future” though, Thomsen said.
Strains and benefits
Implementing the factor VII system has affected production though. “There is a small loss throughout the process. Factor VII is an enzyme so it can digest itself. The longer we spend filtering the longer it has to break down”, Tom Breum Jørgensen, specialist, FVII process at Novo Nordisk, said.
Jorgenson said the nanofilter places “considerable demands on process reliability” and requires extra effort to ensure it remains stable. Despite this, Novo expects the cost of moving to the new system to be covered by future savings.
Novo Nordisk will now use cell-based assays for factor VII and all its other biologics. Discussing the cell-based assays, Pernille Charlotte Svane, director, CMC bioassay at Novo Nordisk, said: “The range of results is far smaller, with greater precision and reliability for us to work with.”