Gamma-Irradiation of Serum for the Inactivation of Adventitious Contaminants

Abstract

Assurance of viral and mycoplasma safety in biopharmaceuticals is best achieved through elimination of animal-derived materials from the manufacturing process. Where this is not possible, the risk of introducing a contaminant through use of the material must be assessed and mitigated. Bovine-sourced serum represents an animal-derived material that is required for certain biopharmaceutical manufacturing processes. Gamma-irradiation of frozen bovine serum was investigated as an approach for mitigating the risk of introducing viral or mycoplasma contaminants. Mycoplasmas in frozen bovine serum were effectively inactivated by gamma-irradiation at 25–40 kGy. The larger viruses tested, respiratory enteric orphan (REO) and Cache Valley virus (CVV), were inactivated completely, while the smaller virus, simian virus type 40, was not inactivated. Gamma-irradiation of bovine-sourced serum is therefore useful for mitigating the risk of introduction of mycoplasmas and many of the viral contaminants found in biologics unprocessed bulk (e.g., CVV, REO virus, epizootic hemorrhagic disease virus). This mitigation strategy is not useful for the smaller viruses (e.g., polyomaviruses, parvoviruses, picornaviruses, caliciviruses).