Ingenza has delivered a new, proprietary biomanufacturing process for human recombinant factor VIII (rhFVIII) to Scottish biotechnology company ProFactor Pharma Ltd (PFP), which will considerably increase global access to low-cost treatment for haemophilia A. The novel bioprocess underpins PFP’s recent signing of a product development, technology transfer and licence agreement with PT Bio Farma (Persero) – Indonesia’s largest pharmaceutical company – paving the way for industrial scale-up of the cost-effective biomanufacturing process, and for clinical trials to begin in Southeast Asia and India.
A global issue
Haemophilia A is a human genetic disorder in which the gene encoding blood clotting factor VIII is defective, meaning the patient does not make sufficient, or any, factor VIII to control bleeding. World Federation of Hemophilia research suggests this disorder affects 1 in 4,000 male births, and that there are more than 660,000 sufferers of haemophilia A worldwide, with only around 191,000 currently receiving treatment. The major unmet need for haemophilia A treatment in many countries is due to the combined constraints of undersupply and exceptionally high cost of treatment with donor-derived or recombinant factor VIII.
A synergistic relationship
Ingenza initially partnered with PFP’s Chief Scientist, Professor John McVey, to establish the highly productive Chinese hamster ovary (CHO) cell line that produces rhFVIII. Ingenza then identified and implemented significant process enhancements to amplify rhFVIII productivity, delivering a low cost of goods sold (COGS) to PFP that will strengthen market competitiveness. Ingenza’s optimisation of the upstream and downstream manufacturing steps for rhFVIII achieved a yield far in excess of the agreed target by essentially reinventing the manufacturing process that PFP had previously developed with an international contract manufacturing organisation (CMO).
A comprehensive service
The 18-month project involved creating and characterising the master and working cell banks, liaising with Charles River Laboratories to undertake preclinical toxicology studies that used rhFVIII material manufactured in-house by Ingenza under GMP-compliant principles. The high process efficiency permitted the toxicology material to be fully manufactured using five-litre scale culture vessels, bypassing the need to scale up to larger systems. Ingenza then carried out formulation development and formulation studies, resulting in a rhFVIII candidate ready for scale up and clinical trials.
Partners in success
As a result of this comprehensive process development and optimization, PFP has now successfully entered the partnership with PT Bio Farma (Persero), opening an estimated $1.36 billion total addressable market for treatment in India, Indonesia, Malaysia, Thailand, Philippines, Singapore and Vietnam, and supporting further global market penetration.
Jaymin Amin, Chief Business Officer of Ingenza, commented: “This collaboration demonstrates Ingenza’s excellence in advancing a customer’s target molecule seamlessly through process feasibility and viability to drug substance manufacture, innovating where appropriate and finally transferring the commercialisation-ready technology. We are excited that this rhFVIII process will ultimately deliver a low-cost and accessible treatment that will be available to every sufferer of haemophilia A, no matter where they live.”