FAQs about Virus Removal Filtration
FAQs about Virus Removal Filtration
Q1. What is the virus removal mechanism of virus removal filtration?
A: The virus removal mechanism of virus removal filtration is based on (1) particle size exclusion--the virus is larger than the pore size of the filter membrane, and the product passes through the filter membrane while the virus is retained. (2) Adsorption mechanism—For viruses whose size is smaller than the membrane pores, the viruses are captured by the forces of charge, van der Waals and hydrogen bonds and so on.
Q2. The principle of virus removal filtration is nanofiltration. What are the requirements for the amount of initial virus added during nanofiltration verification?
A: The industry standard is to try to be lower than 8log.
Q3. Is the virus removal filtration selective for virus types? For example: with or without membrane, DNA or RNA
A: The selection of virus removal membranes needs to focus on the robustness of virus removal, filterability, and amplification performance; the mechanism of virus removal membranes is based on size exclusion, and does not pick the type of virus genome.
Q4. Using membrane to remove viruses, the integrity of the membrane is very important. The integrity standard of virus removal should refer to the manufacturer’s standard or need to set the standard according to the actual situation?
A: Manufacturers have factory tests, and it also needs to be tested during production, based on pre-test results. Non-enveloped viruses use the infection method. Enveloped viruses are based on the principle that the attempted infection method will interfere with the detection method.
Q5. After the process is scaled up (such as 500L to 2000L), do it need to re-verify the virus removal?
A: Process amplification and process changes need to be evaluated in combination with upstream and downstream process changes. Generally, revalidation is required.
Q6. Using membrane to remove virus, if the membrane bag is reused, how to deal with the virus trapped in it?
A: Virus removal filter membranes are generally disposable consumables and will not be reused.
Q7. What need to pay attention to when choosing indicator virus for pH inactivation of virus?
A: In short, enveloped viruses are recommended.
Q8. What are the requirements for virus removal at different R&D stages?
A: For marketing approval, a comprehensive verification based on ICH Q5A is required, and a simplified verification compared to ICH Q5A can be used for phase I, II, and III clinical trial products.
Q9. Why set up a pre-filter?
A: For different samples, when there is no pre-filter, the average mass load of the virus removal filter is 5kg/m², and after using the pre-filter, the average mass load is about 13kg/m2. We can find that by adding a pre-filter, the filtration capacity of some samples can be increased by about 6 times.
Q10. Is the virus clearance work to be done in the first clinical phase or other stages?
A: Virus removal verification needs to be done before clinical.
Q11. Is the virus removal capacity set in volume liters or total protein in kilograms?
A: Virus removal filtration offers two capacities, volume capacity and mass capacity.
Q12. Is the virus removal verification done at the CMC stage?
Need to do before using in human body.
Q13. What is the recovery rate of protein?
A: 98% and above.
Q14. What factors affect the virus removal effect of virus removal filtration?
A: Virus removal filtration can significantly remove viruses, and its removal effect is related to factors such as where virus removal filtration takes place, the concentration of solution, the purity of solution, the filtration pressure and the load and so on.
Q15. What is the difference in retention performance of viruses?
A: Through experiments, we have obtained that there is no difference in the virus retention rate in the feed protein concentration range of 2-24g/L and there is no difference in the filter clogging degree at 89%.
