Viral clearance testing
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.
In preparation for Phase I and Phase III
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.
Virus removal and inactivation steps