To meet the growing demand for oncolytic viruses, there is a need to explore scalable manufacturing processes. While steps such as ultrafiltration/diafiltration and column chromatography are already scalable using existing technologies, scaling up the infection process for licensed product manufacturing typically requires the investigation of bioreactor technology. Potential methods might involve using adherent cells attached to microbeads or suspended cell cultures which can facilitate the production of oncolytic viruses at higher titers. It would be ideal if cell proliferation could occur in a serum-free medium to exclude animal-derived components in line with Good Manufacturing Practice (GMP). High-volume, disposable stirred tank bioreactors designed for single use might be most suitable for virus production. The downstream purification process, particularly the separation from subcellular structures, might necessitate improvements depending on the size and density of the virus particle.

Proper quality control, a critical part of GMP, assures relevant and necessary tests are performed and that all essential materials fulfill acceptable quality standards – this includes sampling, specifications, testing, documentation, and release procedures. By validating and qualifying these processes, we guarantee that our manufactured oncolytic viruses meet the highest standards of purity, potency, and safety for clinical use.

The initial step in the development and manufacture of oncolytic viruses begins with a certified, GMP-compliant master cell bank and a characterized master seed virus. The raw virus supernatant is primarily produced by infecting adherent producer cells at a low rate of infection, and then harvesting the oncolytic virus when extensive cytopathic effect is observed. The purification procedure generally consists of five standard steps that apply to all oncolytic virus platforms, including clarification to eliminate cellular debris, nuclease treatment to break down host cell nucleic acids, ion-exchange/size exclusion chromatography for virus purification, ultracentrifugation or tangential flow ultrafiltration/diafiltration for concentration and buffer interchange, and a terminal sterile filtration step.

In conclusion, the development and manufacture of oncolytic viruses for clinical trials and beyond require careful consideration of scalable production methods and adherence to rigorous quality control standards. By navigating these challenges and partnering with experienced CDMOs, the full potential of oncolytic virus therapies can be realized, offering new hope in the fight against cancer.