Several factors impact virus retention and throughput during a filtration run. Maintaining a optimal flow rate prevents filters from fouling or caps from shearing while maximizing product recovery. Filter integrity tests conducted before and after use confirm filter pores remained intact. Temperature affects both virus infectivity and filter performance—processes are often temperature controlled. Product characteristics like concentration, viscosity and impurities can also influence filter capacity and life. Process parameters are optimized through development and scaled appropriately.
Transitioning a Virus Filtration process from clinical to commercial scale presents unique challenges. Membrane surface area and holder or housing design must scale in tandem with increased biotherapeutic production. Multiple parallels or longer filtration times may be needed at larger volumes. Technology transfer requires characterization of new virus filter lots and operations. Process parameters may require minor adjustments to achieve target performance. Robust in-process controls and continued process verification ensure critical quality attributes are maintained during technology transfers and annual commercial production.
Comprehensive validation is essential to demonstrate effective virus clearance throughout the expected life span of a commercial product. Guidelines outlined in the ICH Q5A document provide a framework for qualification and validation studies. These include media recovery studies to establish virus spiking and analytical methods, inactivation and hold studies to prove virus removal at the wall, and parametric release studies with varied process parameters. Life cycle approaches entail confirmation of validated performance over multiple production cycles and lots. Together, such data provide assurance that commercial processes consistently clear virus to acceptable safety margins.
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