We deliver scalable and robust GMP-compliant manufacturing processes for viral vectors.
At Batavia Biosciences, we operate a range of different manufacturing scales and utilize diverse cell culture equipment for both adherent growth and growth in suspension. The scale ranges from high-throughput 20 mL spin-tubes up to 200 L bioreactors. The equipment ranges from mini bioreactors, shake flasks, WAVE Bioreactors™ , various stirred tank bioreactors to fixed-bed bioreactors (iCELLis® and scale-X™ systems) to support high cell density cell cultures.
We perform state-of-the art manufacturing of diverse viral vectors on par with literature values. For instance, typical yields of 1013 virus particles per liter cell culture of replication-deficient adenoviral vectors are obtained (Vellinga et al, 2014). Typically, 105 viral genomes per cell can be obtained for AAV vectors (Aponte-Ubillus, 2018), and 107 transducing units per milliliter of culture for lentiviral vectors (Merten et al, 2017). For measles vectors, typically 107 TCID50 units/mL are obtained (Grein et al, 2016), whereas for VSV vectors typical titers obtained are 108 plaque forming units per milliliter (Clarke et al, 2016). Here, it must be noted that these reported yields do not take into account variations in transgenes, promotors, production equipment, cell line platforms, cell and virus culture media. Therefore, yields from bioreactor harvests may vary from product to product.
For product-specific protocol development, we utilize Design of Experiments, our generic manufacturing protocols, and our SCOUT® technology. SCOUT technology can be used, to test a large panel of production media and generic feed strategies. In a SCOUT experiment, cultures are scaled down in mini bioreactors to efficiently test various growth conditions to optimize cell growth. The critical deliverables are short cell population doubling times, high cell density and viability. In addition, the SCOUT technology is used to rapidly anchor critical parameters such as multiplicity of infection (MOI), time of harvest and best plasmid transfection practices. Findings from the small scale studies will subsequently be translated to pilot and large-scale protocols to further establish the manufacturing process. For all our viral vector systems, we have generic standard operation procedures (SOPs) available on vector production, which can be used as a basis to develop the product-specific production process.