Abstract
SARS-COVID-19 vaccine supply for the total worldwide population has a bottleneck in manufacturing capacity. Assessment of existing messenger ribonucleic acid (mRNA) vaccine processing shows a need for digital twins enabled by process analytical technology approaches in order to improve process transfer for manufacturing capacity multiplication, a reduction in out-of-specification batch failures, qualified personal training for faster validation and efficient operation, optimal utilization of scarce buffers and chemicals and speed-up of product release by continuous manufacturing. In this work, three manufacturing concepts for mRNA-based vaccines are evaluated: Batch, full-continuous and semi-continuous. Technical transfer from batch single-use to semi-continuous stainless-steel, i.e., plasmid deoxyribonucleic acid (pDNA) in batch and mRNA in continuous operation mode, is recommended, in order to gain: faster plant commissioning and start-up times of about 8–12 months and a rise in dose number by a factor of about 30 per year, with almost identical efforts in capital expenditures (CAPEX) and personnel resources, which are the dominant bottlenecks at the moment, at about 25% lower operating expenses (OPEX). Consumables are also reduceable by a factor of 6 as outcome of this study. Further optimization potential is seen at consequent digital twin and PAT (Process Analytical Technology) concept integration as key-enabling technologies towards autonomous operation including real-time release-testing.
Highlights
With the onset of the COVID-19 pandemic in December 2019, the need for rapid and scalable delivery of vaccines have become urgent
A released batch would be available after nine working days at the earliest, and the last process step, without weekend shifts, would fall into the second week
This assumes close timing of process preparation. This reduces the time required to linearized plasmid deoxyribonucleic acid (pDNA) to four working days, which is a reduction in time of almost more than factor 2
Summary
With the onset of the COVID-19 pandemic in December 2019, the need for rapid and scalable delivery of vaccines have become urgent. Instead of the typical time-to-market of 5–10 years, vaccines are being accelerated to approval in less than nine months [1,2,3]. This shifts the bottleneck in sufficient supply back to production processes, which need to be developed and built in less than nine months, starting with laboratory studies, and ending with technically ready production equipment. In addition to the bottlenecks in material supply and the technical limitations of current manufacturing technology [9,10,11], the shortage of skilled personnel has become apparent [12]
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