Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.
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Ahmadian H, Hansen EB, Faber JH, Sejergaard L, Karlsson J, Bolt G, Hansen JJ, Thim L
Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.
Blood Coagul Fibrinolysis. 2016 Jul;27(5):568-75. doi: 10.1097/MBC.0000000000000477.
- PubMed ID
- 26761578 [ View in PubMed]
- Abstract
Turoctocog alfa (NovoEight) is a third-generation recombinant factor VIII (rFVIII) with a truncated B-domain that is manufactured in Chinese hamster ovary cells. No human or animal-derived materials are used in the process. The aim of this study is to describe the molecular design and purification process for turoctocog alfa. A five-step purification process is applied to turoctocog alfa: protein capture on mixed-mode resin; immunoaffinity chromatography using a unique, recombinantly produced anti-FVIII mAb; anion exchange chromatography; nanofiltration and size exclusion chromatography. This process enabled reduction of impurities such as host cell proteins (HCPs) and high molecular weight proteins (HMWPs) to a very low level. The immunoaffinity step is very important for the removal of FVIII-related degradation products. Manufacturing scale data shown in this article confirmed the robustness of the purification process and a reliable and consistent reduction of the impurities. The contribution of each step to the final product purity is described and shown for three manufacturing batches. Turoctocog alfa, a third-generation B-domain truncated rFVIII product is manufactured in Chinese hamster ovary cells without the use of animal or human-derived proteins. The five-step purification process results in a homogenous, highly purified rFVIII product.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Turoctocog alfa Coagulation factor IX Protein Humans YesActivatorDetails Turoctocog alfa Coagulation factor X Protein Humans YesActivatorDetails