Why raw materials matter
With the validation of the SARS-CoV-2 mRNA vaccines on the global stage, mRNA vaccines and therapeutics are taking the front seat of many biopharma development pipelines. There is an ever-increasing demand for trusted raw materials and manufacturing processes that can lead developers safely down the long and winding road to regulatory approval.
Yet, identifying a raw materials supplier who can scale from preclinical to commercial supply in a cost-effective way is a major roadblock for many drug developers. Finding a company who will be a true development partner, rather than just a supplier of raw materials, is a key to success.
Below we review the mRNA production process and some critical considerations for choosing raw materials to support clinical manufacturing efforts. Discover how Thermo Scientific™ TheraPure™ GMP* solutions can enable mRNA developers to succeed, with raw materials of proven quality and consistency supported by dedicated technical support and partnership.
The mRNA production process
There are several methods for synthesizing mRNA; but cell-free, low-cost, simple, and large-scale production is commonly achieved by in vitro transcription (IVT). IVT-based manufacturing relies on six key steps for mRNA production (Figure 1).
Figure 1. Process for the development of mRNA therapeutics or vaccines.
Successful large-scale mRNA synthesis by IVT depends on three essential components: an RNA polymerase, nucleotides (sometimes chemically modified), and a linear DNA template (Figure 2). Additional enzymes such as restriction endonucleases (for linearization of plasmid DNA templates), RNase inhibitors (for prevention of mRNA degradation), pyrophosphatases (for improvement on mRNA synthesis), and DNase I (for removal of residual plasmid DNA after IVT) are often used.
Figure 2. Key components for successful scale-up of mRNA synthesis.
Choosing the right raw materials for mRNA production
- Quality: Are materials high-purity, animal origin–free (AOF), and b-lactam–free?
- Flexibility: Can raw materials be customized for our unique formulations?
- Compliance: Can appropriate documentation be provided for regulatory bodies?
- Low risk: Do materials have a successful track record of use in approved therapeutics?
- Consistency: Are the materials produced and analyzed by fully validated processes to minimize lot-to-lot variability?
- Scalability: Are adequate quantities and quality of materials available as we move from preclinical to commercial scales?
When to consider GMP-quality materials
Even at the discovery phase, it is important to have a line of sight into raw materials suitable for good manufacturing practices (GMP). As you move into early preclinical phases, research use only (RUO) products are increasingly unsuitable for quality and regulatory purposes. Progressing from preclinical to clinical studies and onto manufacturing, suppliers who can help you scale up, provide quality raw materials, and support regulatory documentation become more critical. Therefore, bringing in GMP-quality materials and their suppliers early in process development enables a smoother transition and lower risk as the development of your mRNA therapeutics and vaccines matures (Figure 3).
Figure 3. Drug development stages and raw material selection.
Accelerate your mRNA production with the TheraPure GMP portfolio
Exploring a supplier of enzymes and NTPs starts before your mRNA enters clinical trials. From preclinical studies to commercial approval, the TheraPure GMP portfolio offers high-quality materials, technical support, and proven quality management to enable successful scale-up of mRNA production (Figure 4).
Figure 4. TheraPure GMP products for mRNA production.
Choose a partner who knows the path from preclinical studies to commercialization. Connect with Thermo Fisher at thermofisher.com/therapure
* “TheraPure GMP” refers to the quality level of the raw, ancillary, or starting materials to be used for further manufacturing. TheraPure GMP products are manufactured in facilities with ISO 9001–certified quality management systems that operate in accordance with relevant good manufacturing practice (GMP) principles, as outlined in ICH Q7 or equivalent guidance documents or standards.
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