Veterinary vaccine production using bioreactors: scale up study from laboratory and pd up to commercial production

Background Vaccination has proven itself as the most effective tool to control and prevent the disease and to facilitate the safe trade of live animals. Viral vaccine manufacturing processes present some specific constraints as compared to other biotech products linked to the cell substrate used and to the viral production. Multiple cell lines are used for productions such as VERO, MDCK, MRC5, BHK, and CHO cells. BHK-21 cells were selected because they are the most commonly used cells for vaccine production. As the feasibility of transferring the BHK-21 cells growth in microcarriers from a conventional bioreactor to single-use bioreactor (SU) was demonstrated, actually was time to scale-up and verify the flexibility and ease of use of these SU bioreactors enable rapid scale-up without any loss in product quality. This document describes a scaled-up production of a bovine viral vaccine. Identification of optimal parameters values, testing at intermediary bioreactors scales (2 liters 50 liters) and application of the new process settings at industrial bioreactor scale of 200 liters were performed. Taking into account that a critical feature of microcarrier-based cell culture is the homogeneity of cell adhesion to the beads, mixing and aeration performance evaluation remain mandatory to ensure robust scale-up of cell culture processes. The goal of this study was to evaluate the possibility to produce the antigens for animal vaccines manufacturing in a bioreactor SU as alternative to roller bottles without any loss in product quality. Evaluation of COG reduction was done.