Evaluation of the virus clearance capacity and robustness of the manufacturing process for the recombinant factor VIII protein, turoctocog alfa

- The virus clearance of the turoctocog alfa purification process was assessed.
- Viruses with different sizes and properties were used: eMuLV, MVM, Reo-3, BEV, IBRV.
- All viruses were effectively removed through a combination of orthogonal steps.
- Virus clearance is robust with respect to process variation and re-use of resins.
- Effective and robust virus clearance is important for the safety of turoctocog alfa.

Turoctocog alfa is a B-domain-truncated recombinant factor VIII protein produced in a Chinese hamster ovary (CHO) cell line. The aim of this study was to evaluate the virus clearance capacity and robustness of the turoctocog alfa purification process. Virus clearance evaluation studies were conducted utilising a scaled-down version of the manufacturing process. Total virus clearance was evaluated using the ecotropic murine leukaemia virus (eMuLV) as a model for non-infectious retrovirus-like particles (RVLPs) and certain enveloped viruses. Other viruses utilised included: infectious bovine rhinotracheitis (IBRV), minute virus of mice (MVM), bovine enterovirus (BEV) and Reo-3 virus (Reo-3). Robust clearance of all model viruses was demonstrated with either new or reused resins. Overall, virus reduction factors were: >18.0 log10 (eMuLV); 11.0 log10 (MVM); >11.8 log10 (Reo-3; >5.0 log10 using nanofiltration); >15.3 log10 (BEV) and >12.7 log10 (IBRV). Taken together, these values demonstrate that the purification process for turoctocog alfa effectively removes a range of enveloped and non-enveloped viruses of different physicochemical properties and sizes.