The plant where Octapharma makes its recombinant Factor VIII candidate – which is next to Lake Malaren in the West of the Swedish capital Stockholm - has been splitting blood plasma to make protein medications since the 1940s.
It is also just a few streets away from the plant at which Swedish Orphan Biovitrum (Sobi) makes the API for Pfizer’s haemophilia A treatment, ReFacto.
But while the Octapharma and Sobi sites may share a common heritage – both were previously owned by Pharmacia – the Factor VIII made at the Octapharma site is very different from the Pfizer product, which is produced in Chinese hamster ovary (CHO) cells.
Site manager Olivier Clairotte told BioPharma-Reporter.com that: “We produce Factor VIII anti haemophilic factors using human cells, specifically human embryonic kidney cells, which is a completely new business for us compared with out plasma fractionation activities.”
He explained that using human cells eliminates the immunogenicity problems associated with recombinant Factor VIII products already approved and on the market.
This claim is supported by research. The immunogenic risk posed by recombinant Factor VIII proteins is due to the presence of antigenic epitopes like alpha-1,3-Gal or N-AcetylNeur-acid, which are introduced as a result of the protein’s expression in hamster cells.
Octapharma produces cultures the HEK cells it uses in fixed, stainless-steel bioreactors according to Clairotte who explained that the firm decided not to use disposable, single-use because such systems are not suitible for the product.
“First with the number of parameters we have to control [when making recombinant Factor VIII] we did not think that single-se was applicable. Then when it comes to cost calculation, in some circumstances single-use is an advantage, but for us it was less important.”
Octapharma does use single-use technology for filtration and other downstream steps Clairotte continued.
“Once we have finalised the cell cultivation we use a series of purification steps to isolate this Factor VIII compound and there we come a lot close to a standard production line with chromatography, ultrafiltration, dialysis and nano-filtration techniques all being used.”
Octapharma also fills the Factor VIII in-house and has invested in what Clairotte described as “an advanced” line – which has six isolators and a freeze-dryer - that will handle both the new product and others made at the facility.
If the recombinant Factor VIII product is approved, the Stockholm site will supply Europe and other markets in which the firm intends to seek approval Clairotte said.
“We have submitted in Europe for marketing authorisation and we will submit soon in the US, Canada. The goal for us is to make the product available globally.”