Process Automation and Control Strategy by Quality-by-Design in Total Continuous mRNA Manufacturing Platforms

Vaccine supply has a bottleneck in manufacturing capacity due to operation personnel and chemicals needed. Assessment of existing mRNA (messenger ribonucleic acid) vaccine processing show needs for continuous manufacturing processes. This is enabled by strict application of the regulatory demanded quality by design process based on digital twins, process analytical technology, and control automation strategies in order to improve process transfer for manufacturing capacity, reduction out-of-specification batch failures, qualified personnel training and number, optimal utilization of buffers and chemicals as well as speed-up of product release. In this work, process control concepts, which are necessary for achieving autonomous, continuous manufacturing, for mRNA manufacturing are explained and proven to be ready for industrialization. The application of the process control strategies developed in this work enable the previously pointed out benefits. By switching from batch-wise to continuous mRNA production as was shown in previous work, which was the base for this study, a potential cost reduction by a factor 5 (i.e., from EUR 0.380 per dose to EUR 0.085 per dose) is achievable. Mainly, based on reduction of personnel (factor 30) and consumable (factor 7.5) per campaign due to the significant share of raw materials in the manufacturing costs (74–97). Future research focus following this work may be on model-based predictive control to gain further optimization potential of potential batch failure and out of specification (OOS) number reduction.