The API (active pharmaceutical ingredient) maker owns BioReliance, a company producing dry powder for cell cultures, and is analysing the roughly 90 chemicals that go into its custom media to reduce unnecessary components.
SAFC’s R&D department aims to discover unnecessary materials in dry powder manufacture which have no bearing on the cell culture process, Kevin Kayser told us, to eliminate the steps that are just a result of habit.
“Over the years, people went to grad school and this was the media formula they used and they’re comfortable with. What they’ve never asked is [for instance] why is ferric sulphate a requirement and at what concentration? A lot of times the mentality was because it was always in there and I need to put it in.”
But, said Kayser, some of the media currently used in biologics manufacturing are a hangover from the days of microbial work, and be necessary for growing bacteria but not for human or CHO (Chinese hamster ovary) cells.
“Why have a raw material in there that you don’t need, and you have to procure?” he asked. “If there’s a world supply interruption of the material, and it doesn’t do anything [for the cell growth] then you’re interrupting your manufacturing for something that doesn’t have a significant impact.”
Raman spectroscopy
The company is also trying to characterise cell culture raw materials to control their variability, Kayser told us. Unknown elements, such as copper, can vary in concentration between vendors and cause inconsistencies for the biologics manufacturers who buy the materials.
“You may put something like ferric sulphate into the media and realise there are trace amounts of copper in that raw material and then every time that you add it you may accumulate higher concentrations of copper.”
The main challenge for raw material characterisation today is building new analytical methods which work quickly, Kayser told us.
“There have been a few papers on raman spectroscopy [a variant of mass spectronomy] where they have hand-held ramans. So you can actually screen a powder and say ‘here’s the fingerprint of the powder, and it’s exactly like the last one.’ So biopharmaceutical companies can do that in the warehouse as they receive the powder for immediate validation.
“There are also techniques to understand parts per billion copper concentration in a specific raw material –a lot of method development is needed.”
Meaningless specs
But consistency in biologics materials has improved since first-generation attempts which removed serum from the process, prompting a move to using plant and yeast extract hydrolysates. Even with these, considerable variability remained, said Kayser.
“I’ve seen specs in the past that said ‘North American fall-harvested wheat from this region,’ trying to control the variability because climate alterations could change the structure of the plants.”
Although detailed, these specs “were not meaningful,” said Kayser. “One year there might be a drought, but you didn’t have drought in your specification.” Companies have since removed hydrolysates and switched to chemically-defined media formulations.