Viral vector production in the integrity® iCELLis® single-use fixed-bed bioreactor, from bench-scale to industrial scale

Abstract

Wild-type or recombinant viruses used as vaccines and human gene therapy vectors are an important development tool in modern medicine. Some have demonstrated high potential such as lentivirus, paramyxovirus and adeno-associated-virus (AAV). These vectors are produced in adherent and suspension cell cultures (e.g. HEK293T, A549, VERO, PER.C6, Sf9) using either transient transfection (e.g PEI, calcium phosphate precipitation) or infection (e.g. modified or recombinant viruses) strategies. Most of these processes are currently achieved in static mode on 2-D systems (Roller Bottles, Cell Factories, etc.) or on suspended microcarriers (porous or non-porous). However, these two systems are time-consuming (large numbers of manipulation, preparation of equipment, etc.) and hardly scalable. In regards to process simplification and traceability, Integrity® iCELLis® bioreactors offer a new solution for scalability and monitoring of adherent cell cultures. The Integrity iCELLis Bioreactor Integrity® iCELLis® bioreactors from ATMI LifeSciences were designed for adherent cell culture applications such as recombinant protein, viral vaccine and gene therapy vector production. Using PET carriers trapped into a fixed-bed, cells grow in a 3-D environment with temperature, pH and dissolved oxygen controls. The iCELLis technology can be used at small-scale (the iCELLis nano from 0.5 to 4 m2) and manufacturing scale (iCELLis 500 from from 66 to 500 m2) which eases process scale-up and its overall utilization.