every biologically manufactured product is at risk of viral contamination which can have
serious clinical and economic implications sources of viral contamination are among
other raw materials equipment cell banks or breaches in cgmp production
major concerns are given by viruses endogenous to the cell line and adventitious viruses to
guarantee patient safety regulatory authorities have defined three principal approaches for viral
safety one the selection of clean source material two the implementation of virus clearance steps
three the testing for known viral contaminants virus clearance steps must be part of all
biologics manufacturing virus filtration low ph inactivation chromatographic steps
to prove the effectiveness of each purification step virus clearances studies must be conducted
before any virus clearance study a model panel of viruses with a variety of physiochemical
characteristics must be chosen every study must represent a valid scaled-down model
to guarantee reliable comparison between the manufacturing and the laboratory processes
virus clearance studies can be divided into pre-study main study and reporting
viruses are spiked into the test
material
the test material is filtered through the virus filter at constant pressure
critical process parameters are monitored samples are taken during the process step
and assayed for viral infectivity these samples are serially diluted
positive and negative controls are included on each day to ensure assay robustness
to determine the effectiveness of the virus clearance step
the log reduction value needs to be calculated the lrv is calculated by comparing the virus titer
before and after the performed purification step virus titus are determined by a tcid
50 assay in which the cytopathic effect cpe is observed and evaluated at various
dilutions of the test samples cpe indicates cell death caused by the infection of the virus
once the main study is finished data is compiled in a virus safety report
to guarantee a reliable result of the tcid 50 assay pre-tests are performed this consists
of cytotoxicity and viral interference testing which are conducted prior to the main study
cytotoxicity and viral interference tests ensure the test material does not impact on cellular
or viral growth therefore avoiding unreliable lrv results in addition to careful study
planning three key aspects must be considered for a successful virus clearance study first correct
product handling such as proper wetting and equilibration of filters and membrane absorbers
second purified virus stocks to prevent fouling of filters and membrane absorbers which could reduce
the clearance effectiveness third valid scale down model to guarantee reliable comparison between the
manufacturing and the laboratory processes we can study different products under various conditions
confidence virus clearance services gives you the confidence you need to
succeed
you