RUNspike, a complementary virus filter spiking method: a solution to the problem of reduced throughput due to the addition of the virus spike.
The traditional approach to virus filter spiking studies (virus added to the feed solution before the start of filtration) can lead to oversized viral filtration systems because of the non-representative volumetric throughputs (L/m2) that can be seen with the addition of the virus spike. The reduction in throughput is thought to be caused by interactions that take place between the species in the virus stock solution alone, or in conjunction with the species in the drug product. The traditional approach assumes that virus filter log reduction value (LRV) is directly related to volumetric throughput and limits manufacturing scale designs to the volumetric throughput achieved in the spiking study. This article references previous work that shows that % flow decay is a more relevant critical parameter than volumetric throughput for a poly(vinylidene diflouride) (PVDF) parvovirus filter. Based on this work, one could design the manufacturing-scale viral filtration system to the representative volumetric throughput achieved without the virus spike and implement a flow decay limit in manufacturing to ensure virus LRV. RUNspike is a complementary method that can be easily implemented today and that goes one step further. The RUNspike method challenges the same total virus as the traditional method, but the virus is added at the end of the filtration, after the representative volumetric throughput has been demonstrated. Comparable RUNspike and traditional LRV data, at the same flow decay, bridges the gap and strengthens the case for the flow decay-based design approach.
Parrella
Joe
J
Millipore Corporation, 900 Middlesex Turnpike, Billerica, MA 01821, USA.
Wu
Yaling
Y
Kahn
David W
DW
Genest
Paul
P
D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry / Q000295:instrumentation / Q000379:methods; D005374:Filtration / Q000379:methods*; D017992:Parvovirus; D004364:Pharmaceutical Preparations / Q000592:standards; D011145:Polyvinyls / Q000737:chemistry; D011786:Quality Control; D014780:Viruses; D005465:Fluorocarbon Polymers
D004364:Pharmaceutical Preparations; D011145:Polyvinyls; C024865:polyvinylidene fluoride; D005465:Fluorocarbon Polymers