Emerging therapeutics such, mRNA vaccines, and viral vector–based gene therapies are more complex than established moieties such as monoclonal antibodies and recombinant proteins. The challenge arises how to produce these new therapies at scale and cost effectively. The higher complexity of viral vectors compared to mAbs creates bioprocess challenges for example, with viral vectors, production and purification scientists must deal with complex quaternary structures for which the biophysics and biochemistry are still not well-characterized.  For many indications, a 100-fold increase in overall process yield of potent vector is required which must come from increased titers during the upstream production and recovery during downstream processes without compromise on critical quality attributes. A large shift in technology innovations must take place to enable industrialization of new modalities bioprocess with a reduced cost in mind. Case studies for AAV and Lentivirus illustrate the benefits of intensification and simplification of the entire process for optimal and cost-effective viral vector manufacturing.  KrosFlo® TFDF® perfusion technology increases overall yield of adeno-associated virus serotype 8 (AAV8) by 3 to 10-fold and lentivirus by more than 50-fold, respectively, compared to their batch bioreactor processes. The single-use advanced KRM™ chromatography system was used to scale-up the affinity chromatograph step from 1-L benchtop-scale to 167-L industrial scale of AAV9. The single-use KRM™ chromatography system was used for scaling up the affinity chromatograph step from 1-L benchtop-scale to 167-L industrial scale of AAV9.  This linear scaleup demonstrated a 240-fold increase in the overall viral recovery, as well as good reproducibility of the scale-up runs without compromising product critical quality attributes such as empty and full capsid ratio, endotoxins, residual host cell proteins and aggregates. Due to the designed KRM™ systems with their low hold-up volumes, gentle internal flow paths, and accurate pump performance, high productivity, and cost-effective viral vector manufacturing such as AAV, lentivirus, and exosomes are enabled.

The production of Advanced Therapeutic Medicinal Products has introduced new manufacturing challenges that require the advancement of classical bioprocess technologies to reduce the cost to levels that will make the therapies affordable by a larger segment of the population. This presentation will describe new manufacturing processes and technologies that will render such processes more cost-efficient with higher yields:​

• Cell culture intensification and reduced number of downstream unit operations to increase yield and reduce cost​

• Self-contained single-use unit operations to prevent contamination and improve product safety​

• In-line product and impurity monitoring and characterization to improve quality and yield