Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.
Blood Coagul Fibrinolysis
; 27(5): 568-75, 2016 Jul.
Article
en En
| MEDLINE
| ID: mdl-26761578
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor VIII
/
Expresión Génica
/
Secuencia de Aminoácidos
/
Eliminación de Secuencia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Blood Coagul Fibrinolysis
Asunto de la revista:
ANGIOLOGIA
/
HEMATOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Dinamarca
Pais de publicación:
Reino Unido