Advanced therapies based on genes, tissues, or cells offer groundbreaking new opportunities to treat incurable diseases. Within these therapies, mRNA offers some unique advantages over other modalities, such as viral vectors. Its manufacture is a cell-free process that reduces the production timeline and makes it relatively simple to produce.
This has increased the demand for mRNA production while adding emphasis on streamlining the manufacturing process of new products. However, although product manufacture and process validation of biotherapeutics are routinely performed in industry, the process for mRNA manufacture is less well established and there are many differences between the manufacturing processes of companies.
BioPhorum’s new paper – Overview of end-to-end mRNA drug substance and drug product manufacturing processes and scale-up considerations – provides some much-needed clarity in this area.
It offers a starting point for developers who want to create their own process flow. It can also be used by anyone who wants to understand more about the manufacturing of mRNA and what each step entails, the capabilities, parameters, and equipment used.
“The flexibility of the mRNA platform enables accelerated development timelines to quickly address various diseases,” said Tatenda Shopera, Principal Scientist – Bioprocess R&D Upstream Process Development at Pfizer. “It’s great to see biopharmaceutical industry leaders coming together to provide great fundamentals to address scale-up challenges of this exciting modality and to enable medicines and vaccines to get to patients faster.”
It also highlights different challenges in sizing up from lab to GMP scale, the limitations at current commercial size, and possible desired future scales. This makes it a great tool if you are assessing and preparing for the scale-up process of mRNA manufacturing.
At an industry level, our paper can be used in discussions on scale-up challenges and their solutions, and guide conversations around the commercialization of mRNA manufacture.
“This article brings forth the joint knowledge and experience of multiple industry SMEs and leaders,” said Akhilesh Bhambhani, Head of the Drug Product Development – Technical Development/Technical Operations at Ultragenyx Pharmaceutical Inc. “It provides valuable insights and a high-level overview of mRNA/LNP processes starting from plasmid linearization to fill/finish operation as well as scale-up considerations.”
It discusses the approaches to manufacturing mRNA encapsulated in lipid nanoparticles (LNPs) across different unit operations for manufacturing drug substance / drug product. The mRNA/LNP product manufacture process flow map is split into four groups:
- Plasmid linearization
- mRNA manufacture
- mRNA/LNP manufacture
- Fill and finish through QA release.
Our paper was developed by experts in BioPhorum’s Cell and Gene Therapy RNA workstream to enable future discussions and accelerate the commercialization of mRNA therapies.
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