Meet the Expert: Ahd, Bioprocess Project Director
Current costs of biopharmaceutical manufacturing often prevent segments of the world’s population from accessing critical medicines or even prevent medicines from being marketed. A significant part of these costs come from the need for large and expensive manufacturing facilities. This hurdle can be overcome by significantly intensifying the bioprocesses and therewith reducing operational costs and capital investments.
Several initiatives are being taken to intensify the upstream production of biopharmaceuticals, like recombinant proteins, viral vectors and vaccines. An example of a process intensification method is for example with CRISPR gene editing technology. Scientists are able to genetically modify producer cell lines resulting in more product per cell. Next to improving the cell lines, many innovations are done to enable high cell densities of adherent cell cultures in bioreactors. An example is the use of supplemented (defined) media that can also result in more product per cell. Some lipids can contribute to higher yields when supplemented to a cultivation medium. Process intensification can also be realised by intensifying the equipment used. The rise of fixed-bed bioreactors, containing a porous pre-packed bed able to significantly increase volumetric productivity and providing a shear stress-free environment is a clear example.
A steady increase of titres in the upstream process (USP) and the corresponding change in impurity profile can present a challenge for development and optimization of downstream processes (DSP). The availability of DSP capable of handling these increasing quantities and concentrations are becoming a bottleneck for many biopharmaceutical manufacturing processes. DSP should deliver biopharmaceuticals with levels of purity and biological activity at par with regulatory standards, irrespective of the changes in the USP. Initiatives being taken in the DSP field focus mostly on increasing the product recovery and minimizing the number of process steps. An example is the use of continuous systems to achieve process efficiency and the use of novel membrane materials that allow a much faster process time and high recoveries.
At Batavia Biosciences, our team developed a highly intensified production process for inactive polio vaccine based on Sabin strains (Sabin-IPV), called HIP-IPV™. It enables fast and low-cost manufacturing for all in need. It can be easily implemented by vaccine manufacturers to deliver large volumes of Sabin-IPV at very low cost. It uses an equipment component, the NevoLine™ biomanufacturing platform, developed and marketed by Univercells. The production process uses the scale-X™ bioreactor, based on a novel fixed-bed design that delivers very high cell densities and volumetric virus yields up to 40-fold higher than traditional technologies. In addition, high efficiency purification membranes and state-of-the-art process intensification know-how increase process output by a factor of up to 80-fold. This process intensification allows miniaturization of the manufacturing process and equipment to such an extent that the output of a 1,200 L bioreactor can be delivered by a 60 L bioreactor, and the entire process is contained in a NevoLine system with a footprint of 10 m2. Such miniaturization makes commercial manufacture possible at lab scale, massively reducing costs for manufacturing these vaccines. CoGs modelling using current yields obtained at small scale indicate a fully loaded CoGs of <$0.30 per trivalent dose of drug product, an approximate 5-fold reduction compared to the current IPV prices. Moreover, the vaccine can be produced in a small footprint facility based on four NevoLine systems, costing approximately $30-40M and capable of delivering 40M trivalent doses per year.
As a company dedicated to help bringing biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate, Batavia Biosciences has vast experience in deploying the latest bioprocess technologies to optimize biopharmaceutical production. With our team of experienced biopharmaceutical experts, we are well equipped to take on any challenge associated with process development.