We prepare your submission to the regulatory authorities with a comprehensive viral clearance study report.
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.
Virus removal and inactivation steps
Vironova Biosafety operates in compliance with OECD GLP guidelines and is included in the regular inspection plan of the Swedish Board for Accreditation and Conformity Assessment (SWEDAC). As stated in ICH Q5A, manufacturers of biologics are required to prove the viral removal and/or inactivation efficacy in their manufacturing process, and viral clearance studies are required to be performed in compliance with GLP principles.
Note: We also offer customized non-GLP viral clearance studies!
An important aspect of viral clearance is how well the virus reducing steps will tolerate variations outside the limits set of the process parameters. This is referred to as robustness and is increasingly emphasized by the authorities. It should be performed in a separate set of experiments where virus reduction is measured under conditions that deviate from the original limits. The robustness studies should also be performed with several viruses with different properties.
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 setup.
Alternatively, a digital droplet PCR (ddPCR) is used to measure the amounts of viral genomes before and after the process step. The virus reduction capacity of the process step is then calculated and presented as a logarithmic reduction value (LRV).
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 end-point-dilution 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.
The Vironova Biosafety services team have a broad research background and experience of a wide range of biologics. We can help you to plan a specific study or solve a tricky problem. Whatever your need, you can contact Vironova Biosafety by sending an e-mail to email@example.com or by using the form on our contact us page.