Scalable mRNA Machine for Regulatory Approval of Variable Scale between 1000 Clinical Doses to 10 Million Manufacturing Scale Doses

The production of messenger ribonucleic acid (mRNA) and other biologics is performed primarily in batch mode. This results in larger equipment, cleaning/sterilization volumes, and dead times compared to any continuous approach. Consequently, production throughput is lower and capital costs are relat...

Full description

Saved in:
Bibliographic Details
Published in:Processes 2023-03, Vol.11 (3), p.745
Main Authors: Hengelbrock, Alina, Schmidt, Axel, Helgers, Heribert, Vetter, Florian Lukas, Strube, Jochen
Format: Article
Language:English
Subjects:
Automatic control
Capital costs
Clinical trials
Comparative analysis
Contamination
Continuous production
Deoxyribonucleic acid
DNA
Enzymes
FDA approval
Manufacturing
Mathematical analysis
Membrane separation
Messenger RNA
Plug flow chemical reactors
Quality assurance
Real time
Regulatory approval
Ribonucleic acid
RNA
RNA polymerase
Severe acute respiratory syndrome coronavirus 2
Solvents
Stainless steel
Sterilization
Technology assessment
Vaccines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The production of messenger ribonucleic acid (mRNA) and other biologics is performed primarily in batch mode. This results in larger equipment, cleaning/sterilization volumes, and dead times compared to any continuous approach. Consequently, production throughput is lower and capital costs are relatively high. Switching to continuous production thus reduces the production footprint and also lowers the cost of goods (COG). During process development, from the provision of clinical trial samples to the production plant, different plant sizes are usually required, operating at different operating parameters. To speed up this step, it would be optimal if only one plant with the same equipment and piping could be used for all sizes. In this study, an efficient solution to this old challenge in biologics manufacturing is demonstrated, namely the qualification and validation of a plant setup for clinical trial doses of about 1000 doses and a production scale-up of about 10 million doses. Using the current example of the Comirnaty BNT162b2 mRNA vaccine, the cost-intensive in vitro transcription was first optimized in batch so that a yield of 12 g/L mRNA was achieved, and then successfully transferred to continuous production in the segmented plug flow reactor with subsequent purification using ultra- and diafiltration, which enables the recycling of costly reactants. To realize automated process control as well as real-time product release, the use of appropriate process analytical technology is essential. This will also be used to efficiently capture the product slug so that no product loss occurs and contamination from the fill-up phase is
ISSN:2227-9717
2227-9717
DOI:10.3390/pr11030745