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Written by expert: Ahd, Director Project Management

Current costs of biopharmaceutical manufacturing often prevent segments of the world’s population from accessing critical medicines. Sometimes the costs even prevent medicines from being marketed. A significant part of these costs come from the need for large and expensive manufacturing facilities. Significant bioprocess intensification can help overcome this hurdle. Intensification of a process reduces operational costs and capital investments.

Upstream bioprocess intensification

The biopharmaceutical industry took several initiatives to intensify the upstream process of biopharmaceutical production. An example of a process intensification method is CRISPR gene editing technology. Using this 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. For instance, the use of supplemented (defined) media 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 is a clear example. These bioreactors contain a porous pre-packed bed able to significantly increase volumetric productivity. Additionally, they provide a shear stress-free environment which is beneficial for cell growth.

Downstream bioprocess intensification

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. For example, process efficiency is achieved by the use of continuous processing. Also, the use of novel membrane material is trending. These membranes allow faster processing and high recoveries compared to conventional membranes.

Case study: highly intensified Sabin-IPV production

Our team developed a highly intensified production platform called HIP-Vax®. The first process developed on this platform was for the Inactivated Polio Vaccine based on Sabin strains (Sabin-IPV). Above all, this platform enables fast and low-cost manufacturing. Also, vaccine manufacturers worldwide can easily implement this platform to deliver large volumes. For the IPV process, the NevoLine™ biomanufacturing equipment is used. The upstream process uses the scale-X™ bioreactor, which is a novel fixed-bed design. This bioreactor 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 the process output by a factor of up to 80-fold. This process intensification allows miniaturization of the process and equipment to such an extent, that the output of a traditional 1,200 L bioreactor can be delivered by a 60 L bioreactor.

A NevoLine system, with a footprint of 10 m2, contains the entire process. Such miniaturization makes commercial manufacture possible at lab scale. Therefore, it massively reduces the manufacturing costs of these vaccines. CoGs modeling using current yields obtained at small scale indicates a fully loaded CoGs of <$0.30 per trivalent dose of drug product. This is an approximate 5-fold price reduction of the current IPV prices. Moreover, a small footprint facility based on four NevoLine systems can produce the vaccine. This facility would cost approximately $30-40M and is capable of delivering 40M trivalent doses per year. In addition to inactivated vaccines, Batavia Biosciences also uses the HIP-Vax production platform for vectored vaccines. In conclusion, the wide applicability of this platform makes it suitable for urgent and cost-effective response to epidemics or pandemics, such as the current SARS-CoV-2 pandemic.

We are dedicated to help bring 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. Our experienced biopharmaceutical experts are well equipped to take on any challenge associated with process development.