Advances in Sterilization Technologies for Overcoming Viral-Vector Manufacturing Challenges

Posted: 6 May 2024

Sterility must be assured for all biologic drug products and typically requires use of aseptic manufacturing techniques. Viral vectors are sterilized via sterilizing-grade final filtration followed by aseptic filling. Filtration of highly concentrated formulations is a key challenge, as is avoidance of microbial and cross-contamination due to manual errors. Indeed, sterility loss can also occur during upstream and other downstream unit operations prior to filtration. Furthermore, the specific attributes of the virus involved must be considered when developing specific processes. Lentiviral (LV) vectors are close to the pore size of sterile filters, while others (such as poxvirus vectors) are much larger and this type of filtration is not possible. Enveloped viruses, meanwhile, are often susceptible to excessive thermal or pH conditions.

Manufacturing low-volume/high titer advanced therapy products can be challenging due to limited access to GMP single-use equipment (bioreactors, chromatography systems) designed for smaller batch volumes. Suppliers have responded with the introduction of smaller single-use mixers and small tangential-flow filtration (TFF) systems with peristaltic pumps and single-use tubing for performing buffer exchange at extremely low volumes, especially at the end of manufacturing processes.

Filter screening studies are essential to identifying sterile filtration solutions that afford the best product yield and quality and minimize product losses. Customized single-use manifolds and filtration systems can reduce hold-up volumes, which is particularly important for small-volume products. Implementation of automated systems helps to minimize operator error. Close collaboration between suppliers and manufacturers with regards to design and suitability testing of potential new solutions is crucial to ensuring they improve efficiency, productivity, quality, and safety.