Module 9 2021

19/03/2021

Virus Clearance Validation-Endogenous CHO Retrovirus-Ensuring Virus Safety for Biopharms Many cell lines, particularly rodent cell lines, contain endogenous virus-like particles e.g. NS0, CHO Regulatory authorities require that any purification process is shown capable of ‘clearing’ several logs in excess of the estimated viral load ● Each purification step assessed for ability to clear retrovirus and parvovirus ● Assessment carried out using two independent experiments ● Product specific virus clearance validation TEM is used to visualise and quantify virus in a cell line or bulk harvest to determine the load Risk is mitigated by carrying out virus clearance validation and a dose risk factor is calculated to give < 1 retrovirus like particle per 10^6 doses. For vaccines and gene therapy products there is no VCV ● Risk is mitigated by QC testing in process and product ● Closed processing where possible ● Sourcing raw materials from accredited sources accompanied by certification that demonstrates virus testing and irradiation for example ● HTST or filtration of media

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C-type: Round, enveloped, mature particles with electron-dense core - characterised by ‘budding’

• For phase I/II/III submissions 2 viruses are required and validation of virus reduction should be • performed prior to the onset of the clinical trial (First Time in Man) • For BLA/MAA 4 model viruses expected with a range of physicochemical properties • BLA/MAA include spike clearance on end of column lifetime to show the claim hasn’t changed

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