The baculovirus expression vector system: a modern technology for the future of influenza vaccine manufacturing.

INTRODUCTION: Influenza is a vaccine-preventable disease. Due to the evolving nature of influenza viruses, the composition of vaccines has to be updated annually. Most of the current influenza vaccines are still produced in embryonated chicken eggs, a well-established process with some limitations. AREA COVERED: This review focuses on the recombinant DNA technology using baculovirus expression vector system a modern method of manufacturing licensed influenza vaccines. The speed, scalability, biosafety and flexibility of the process, together with the reliability of the hemagglutinin in the vaccine, represent a significant advance toward new platforms for vaccine production. EXPERT OPINION: The scenario of vaccine production in the next years seems to be particularly interesting, involving a transition from the current egg-based production to new technologies, such as the cell culture platform, the RNA technology, the plant-based system, and the DNA vaccine. This latter offers great advantages over egg- and cell-based influenza vaccine production. The universal vaccine remains the goal of researchers and ideally would avoid the need for annual reformulation and re-administration of seasonal vaccines. The lesson learned from the COVID-19 pandemic highlights the importance of having different technologies available and able to promptly respond to a great demand of vaccines worldwide.

Upstream cell culture process characterization and in-process control strategy development at pandemic speed.

As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, and controls (CMC) process development at pandemic speed are required to address this highly unmet patient need. CMC development consists of early- and late-stage process development to ensure sufficient mAb manufacturing yield and consistent product quality for patient safety and efficacy. Here, we report a case study of late-stage cell culture process development at pandemic speed for mAb1 and mAb2 production as a combination therapy for a highly unmet patient treatment. We completed late-stage cell culture process characterization (PC) within approximately 4 months from the cell culture process definition to the initiation of the manufacturing process performance qualification (PPQ) campaign for mAb1 and mAb2, in comparison to a standard one-year PC timeline. Different strategies were presented in detail at different PC steps, i.e., pre-PC risk assessment, scale-down model development and qualification, formal PC experiments, and in-process control strategy development for a successful PPQ campaign that did not sacrifice quality. The strategies we present may be applied to accelerate late-stage process development for other biologics to reduce timelines.