How mRNA vaccine & therapeutic platforms influence facility design
C. Jomary, PhD

Since the emergence of COVID-19 mRNA vaccines, significant manufacturing advances have been made for expanding mRNA vaccines and therapeutics applications. Improvement of mRNA synthesis and purification, mRNA sequence modification and optimization, and the refinement of lipid nanoparticle (LNPs) delivery systems have accelerated mRNA development for wide-ranging therapies, from cancer vaccines to gene therapy and infectious disease treatments. The various manufacturing process platforms developed have specific requirement needed to be taken into consideration when designing multi-products facilities. Designing adaptable facilities for rapid turn-over change to manufacture different products creates an easier and more cost-effective way to expand manufacturing capabilities as the products demand grows.
mRNA manufacturing platforms
The full manufacturing process from DNA template to mRNA final product encompasses three main stages. The first step is to design and produce the mRNA template target. The second step is to synthetize the mRNA using an enzymatic reaction called in vitro transcription. Finally, the mRNA is encapsulated in lipids prior to filtration / sterilization and filling. While these manufacturing steps seem relatively straightforward, they still present many technical and cost control challenges. The different process platforms developed, the mRNA products application - either vaccines or therapeutics, and the scale of production pre-clinical versus commercial manufacturing, will obviously impact the facility design.
mRNA-LNP formulation platforms
The mRNA manufacture scale and target, vaccines versus therapeutics, and the product clinical phase and commercial application influence the mRNA encapsulation equipment selection. In addition, the manufacturing of various mRNA products requires a multiproduct manufacturing facility with a flexible design. The mRNA LNP encapsulation microfluidic equipment selected, stainless steel versus single use, will also impact the facility footprint.
Regulatory consideration
One other challenge for mRNA product manufacturing and facility design resides in current regulatory ambiguities. Although the present regulatory framework does not strictly apply or mention mRNA therapeutics, the US Food and Drug Administration and the European Medicines Agency have produced guidelines on the formulation of mRNAs with lipid nanoparticles. Preventive and therapeutic mRNA vaccines against infectious diseases are currently not considered gene therapy medicinal products but follow vaccine regulations as biological products. However, mRNAs produced from a recombinant source - linearized plasmid that have a mechanism of action related directly to the product genetic expression of the mRNA sequence is considered by EMA as a gene therapy product. Harmonization between regulatory agencies and further clarification of regulatory criteria is required to mitigate potential regulatory risks.

This presentation will walk the audience through mRNA process design, manufacturing equipment selection and their impact on mRNA multiproduct facility design. We will explore single use solutions for closing off open manipulations and reduce cross contamination, and cleanroom design approach to enable cost-effective manufacturing.