Evaluation of Viral Inactivation Efficacy of a Continuous Flow Ultraviolet-C Reactor (UVivatec)
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Viral safety is an important prerequisite for clinical preparations of all biopharmaceuticals derived from plasma,cell lines, or tissues of human or animal origin. To ensure the safety, implementation of multiple viral clearance (inactivation and/or removal) steps has been highly recommended for manufacturing of biopharmaceuticals. Of the possible viral clearance strategies, Ultraviolet-C (UVC) irradiation has been known as an effective viral inactivating method. However it has been dismissed by biopharmaceutical industry as a result of the potential for protein damage and the difficulty in delivering uniform doses. Recently a continuous flow UVC reactor (UVivatec) was developed to provide highly efficient mixing and maximize virus exposure to the UV light. In order to investigate the effectiveness of UVivatec to inactivate viruses without causing significant protein damage, the feasibility of the UVC irradiation process was studied with a commercial therapeutic protein. Recovery yield in the optimized condition of 3,000 J/㎡ irradiation was more than 98%. The efficacy and robustness of the UVC reactor was evaluated with regard to the inactivation of human immunodeficiency virus (HIV), hepatitis A virus (HAV), bovine herpes virus (BHV), bovine viral diarrhea virus (BVDV), porcine parvovirus (PPV), bovine parvovirus (BPV), minute virus of mice (MVM), reovirus type 3 (REO), and bovine parainfluenza virus type 3 (BPIV). Non enveloped viruses (HAV, PPV, BPV, MVM, and REO) were completely inactivated to undetectable levels by 3,000 J/㎡ irradiation. Enveloped viruses such as HIV, BVDV, and BPIV were completely inactivated to undetectable levels. However BHV was incompletely inactivated with slight residual infectivity remaining even after 3,000 J/㎡ irradiation. The log reduction factors achieved by UVC irradiation were ≥3.89 for HIV,≥5.27 for HAV, 5.29 for BHV, ≥5.96 for BVDV, ≥4.37 for PPV, ≥3.55 for BPV, ≥3.51 for MVM, ≥4.20 for REO, and ≥4.15 for BPIV. These results indicate that UVC irradiation using UVivatec was very effective and robust in inactivating all the viruses tested.
Abstract
Viral safety is an important prerequisite for clinical preparations of all biopharmaceuticals derived from plasma,cell lines, or tissues of human or animal origin. To ensure the safety, implementation of multiple viral clearance (inactivation and/or removal) steps has been highly recommended for manufacturing of biopharmaceuticals. Of the possible viral clearance strategies, Ultraviolet-C (UVC) irradiation has been known as an effective viral inactivating method. However it has been dismissed by biopharmaceutical industry as a result of the potential for protein damage and the difficulty in delivering uniform doses. Recently a continuous flow UVC reactor (UVivatec) was developed to provide highly efficient mixing and maximize virus exposure to the UV light. In order to investigate the effectiveness of UVivatec to inactivate viruses without causing significant protein damage, the feasibility of the UVC irradiation process was studied with a commercial therapeutic protein. Recovery yield in the optimized condition of 3,000 J/㎡ irradiation was more than 98%. The efficacy and robustness of the UVC reactor was evaluated with regard to the inactivation of human immunodeficiency virus (HIV), hepatitis A virus (HAV), bovine herpes virus (BHV), bovine viral diarrhea virus (BVDV), porcine parvovirus (PPV), bovine parvovirus (BPV), minute virus of mice (MVM), reovirus type 3 (REO), and bovine parainfluenza virus type 3 (BPIV). Non enveloped viruses (HAV, PPV, BPV, MVM, and REO) were completely inactivated to undetectable levels by 3,000 J/㎡ irradiation. Enveloped viruses such as HIV, BVDV, and BPIV were completely inactivated to undetectable levels. However BHV was incompletely inactivated with slight residual infectivity remaining even after 3,000 J/㎡ irradiation. The log reduction factors achieved by UVC irradiation were ≥3.89 for HIV,≥5.27 for HAV, 5.29 for BHV, ≥5.96 for BVDV, ≥4.37 for PPV, ≥3.55 for BPV, ≥3.51 for MVM, ≥4.20 for REO, and ≥4.15 for BPIV. These results indicate that UVC irradiation using UVivatec was very effective and robust in inactivating all the viruses tested.
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