We deliver scalable and robust GMP-compliant processes for viral vectors.
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 up to 200 L bioreactors. The equipment ranges from mini bioreactors, shake flasks, WAVE Bioreactors™ and different stirred tank bioreactors to a range of iCELLis® equipment (iCELLis® Nano and 500 systems). The most recent addition to our manufacturing platforms is the novel scale-X™ high cell density bioreactor.
We perform state-of-the art manufacturing of diverse viral vectors on par with literature values. For instance, typical yields of 1013 virus particles of replication-deficient adenoviral vectors are obtained per liter cell culture (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 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 our generic manufacturing protocols and our SCOUT® technology. Hereto, a large panel of production media and generic feed strategies are available for testing in mini-bioreactors to optimize (packaging) cell growth. The critical deliverables are short cell population doubling times, extended culture time and high cell densities. 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. 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.