Validation of continuous viral clearance

A method for assessing and validating continuous viral clearance via viral inactivation at a pH level ≤4, comprising

• a) providing a stream or a product stream from a continuous chromatography process to be assessed and validated, wherein the stream or product stream has already passed through a chromatography unit operation in the continuous chromatography process,
• b) spiking the stream or product stream in a valid manner to ensure the spiking is carried out reproducibly and that a desired level of viral particle load is always reached,
• c) performing viral clearance via viral inactivation at a pH level ≤4,
• d) sampling the spiked stream or product stream for a switch time of the chromatography unit operation,
• wherein sampling comprises:
• sampling the spiked stream or product stream in a back to front sampling, and by using a buffer, immediately neutralizing the pH value of each spiked stream or product stream drop to ˜pH 7 when the spiked stream or product stream enters a sampling container to ensure the viral clearance step is reliably stopped upon sampling, and
• e) analyzing the sample of the spiked probe of step d) to quantify viral particles in order to validate and determine viral clearance.