Replacing Traditional Aseptic Process Simulations with Qualification of Cell and Gene Therapy (CGT) Supernatant.

Abstract

Aseptic process simulations (APS) are traditionally performed using Tryptic Soy Broth (TSB) as a surrogate for finished product to qualify aseptic manufacturing operations. In this study, the supernatant from cell processing media was examined for bacterial and fungal growth viability to determine equivalency with TSB. With the use of cell processing media in Cell and Gene Therapy (CGT) manufacturing, can qualifying the supernatant collected from the process eliminate the need for an APS run?Supernatant was collected from cell processing media and incubated at same incubations conditions required for the APS post sterility check (Test A - 7d 20-25°C/7d 30-35°C) and at use conditions (Test B - 14 d at 35°C/5%CO/5%O2). Post incubation, growth promotion testing was performed using ATCC cultures (Ab+, Bs+, Ca+, Ec+, Sa+, Pa+ and Se+), which resulted in growth for Tests A-B and the positive inoculum control. Results concluded that the cell processing supernatant examined was equivalent to TSB, thereby implying that each cell therapy manufacturing run is aseptically self-validating. As more practical approaches emerge for APS qualifications in CGT manufacturing, this data can be used to implement alternate options to qualify a CGT manufacturing process and help establish guidelines for future cell therapy APS qualifications.