Viral clearance studies are mandatory for pharmaceutical production processes where material of human or animal origin is included. The objectives are firstly to find the process steps that may inactivate or remove viruses and secondly to estimate the overall virus reduction obtained by the manufacturing process.
Viral clearance is performed before Phase I and Phase III clinical trials. For the early phase, testing should be performed with one enveloped virus (preferable a retrovirus) and one small non-enveloped model virus. At least two orthogonal steps should be assessed, that is process steps where different mechanisms are responsible for virus inactivation/removal. The study is set up to cover the limits or set points of the process parameters.
It is advisable, as soon as the final manufacturing process has been established, to start full viral validation which should be completed prior to roll out of Phase III studies. Now the process is assessed for its ability to reduce at least four viruses, enveloped and non-enveloped, with different characteristics. An estimate of the robustness of the viral clearance steps may also be needed at this stage.
The study is designed and executed by qualified professionals in partnership with the client. This involves identification of process steps that are effective in removing or inactivating viruses and selection of the most appropriate viruses. A Study Director, assigned for each study, will be your main contact person while the study is in progress. A comprehensive, QA-audited, Study Report will provide all necessary information for submission to the Regulatory Authorities.
At the beginning of a viral clearance study, preliminary studies are performed to evaluate whether protein solutions or buffers are cytotoxic to indicator cells and whether they interfere with the ability of the indicator cells to be infected with the virus.
For each process step to be evaluated for its virus inactivation/removal capacity, material is withdrawn from the previous manufacturing process step, a known amount of virus is added (spiking) and the sample is processed in a down-scaled version of the manufacturing process step. The amount of infectious virus before and after the down-scaled process step is measured by infecting indicator cells in an end-point-dilution set up. The virus reduction capacity of the process step is calculated and presented as a logarithmic reduction value (LRV). Upon request our team of qualified professionals at Vironova Biosafety will conduct the entire viral clearance study or work together with the client.
To increase the sensitivity of the assay and consequently improve the log reduction value, we recommend performing a large volume plating (LVP) for relevant fractions of the processed material in which no virus is expected.