Intensification of Influenza Virus Purification: From Clarified Harvest to Formulated Product in a Single Shift

M. Tajnik Sbaizero, M. Wolschek, M. Reiter, T. Muster, Pete Gagnon and Aleš Štrancar

BioProcess International, 15 October 2018

Abstract:
Influenza is a global respiratory disease with an estimated mortality of up to a half million people per year. The majority of traditional influenza vaccines are still produced in eggs. Downstream processing typically consists of clarification by centrifugation, concentration by ultrafiltration, and purification by ultracentrifugation. Recombinant vaccines are most often purified by chromatography. Chromatographic purification of viruses already has achieved major improvements in recovery and scalability, but it also is important because it enables virus purification to keep pace with important regulatory and manufacturing trends across the field of biopharmaceuticals. One of those trends is process intensification, referring to development of processes that harmonize integration of fewer and more capable steps to achieve higher productivity and reproducibility as well as reduce manufacturing costs.
In this report we describe processes for purification of influenza A and influenza B, both lacking TFF steps, and both using a single chromatography step with a cation exchange monolith on a single-use basis. The choice of process buffers enables final formulation by simple dilution of the product pool. DNA digestion requires two hours. Capture, purification, and formulation are achieved within four hours. Host-cell DNA and host-cell protein (HCP) are reduced more than 99%, and final virus recovery is 80%.