Preparation and characterization of virus spikes for viral clearance studies
The risk of viral contamination is a feature common to all biotechnology products produced by processes that use cell lines and raw materials of animal origin. Such contamination could have serious clinical consequences and worldwide regulatory bodies expect that the viral safety of these products be assured.
Viral clearance studies are performed as one way of demonstrating viral safety. The studies are executed by intentionally adding or “spiking” large amounts of virus into the starting material for individual manufacturing steps and assessing the capacity of those steps to eliminate infectious virus from the product stream.
Spiking virus preparations are considered to be critical reagents in viral clearance studies. Last year, the Parenteral Drug Association issued Technical Report 47: Preparation of Virus Spikes Used for Viral Clearance Studies. Dr. Kate Bergmann, manager, Viral Clearance and Viral Safety, and Dr. Jeri Ann Boose, director, Biopharmaceutical Services were both members of the task force that authored the document.
The technical report emphasizes that virus stock preparation must be well controlled and that the resulting stocks should be tested for identity, strength, and purity. The report highlights that the desired level of purity of the stock preparation used to challenge individual clearance steps is dependent upon the location of the step in the manufacturing purification process. Specifically, crude virus preparations are considered appropriate for challenging early steps in purification, whereas purified virus stocks are preferred for challenging later steps in the process.
Lancaster Laboratories provides numerous well characterized virus stocks for clearance studies. In addition to meeting PDA recommendations concerning identity, strength and purity, several levels of purification are offered for the most commonly used viruses.
Lancaster Labs’ Viral Clearance Team recently participated in a collaborative study with Genzyme and Millipore to demonstrate the impact of virus stock purity on a filtration step commonly used in manufacturing. A paper reporting the results of this study was published in the March issue ofBioProcess International. In addition, the paper has been presented at numerous viral safety conferences, most recently at the IBC Antibody Production Conference in March and the ISBioTech Annual Meeting in April in collaboration with Dr. Damon Asher from Millipore.