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Raw materials for GMP mRNA manufacturing |
Help accelerate mRNA therapeutics research and commercialization by sourcing the right raw materials. Thermo Fisher Scientific helps provide a wide range of products and services throughout every stage of your mRNA therapeutic development cycle such as research and discovery, pre-clinical development, clinical development, and commercial manufacturing.
Figure 1. mRNA manufacturing workflow
Quality grades for RNA-based drug development
- Standard grade—Supporting RNA discovery and research. Wide selection of materials for basic RNA research. These high-quality reagents usually contain animal origin (AO) components in their formulations and production process and are supported with standard quality documentation package.
- TheraPure grade—Advancing early development and process optimization. TheraPure grade materials are an exceptional choice for your initial stages of RNA drug manufacturing process development, optimization, and preclinical studies. The portfolio of animal origin free (AOF) and beta lactam free materials support a smooth transition to TheraPure GMP as it utilizes the same molecule and composition as in TheraPure GMP reagents.
- TheraPure GMP grade—Designed to meet clinical and commercial demands. As your mRNA production progresses toward clinical trials and commercial cGMP manufacturing, you can easily transition to TheraPure GMP materials—manufactured with stringent process and quality controls and accompanied by comprehensive documentation to support regulatory submissions. Watch this quality tour video to learn more.
Quality grades of products differ in variety of attributes, manufacturing processes, quality control documentation package available. See Table 1 for main attributes.
Table 1. Attributes of the various grades of raw materials used in mRNA manufacturing
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| AOF (animal origin free) and beta-lactam free process and materials | No | Yes | Yes |
| AOF and beta-lactam free facility | No | No | Yes |
| Manufacture and documentation follow ICH Q7 guidelines | No | No | Yes |
| Validated product-specific manufacturing processes and analytical methods | No | No | Yes |
| Product-specific stability | No | No | Yes |
| Impurity testing, including melamine and nitrosamine | No | No | Yes |
| Quality documentation | CoA, CoO | CoA, CoO, TSE/BSE statement | CoA, CoO, TSE/BSE statement, impurity profiles |
| DMF (drug master file) | No | No | Yes |
| Recommended use | Research use only | Proof of concept, research, and pre-clinical development | Clinical and commercial manufacturing |
Raw materials for RNA therapeutics: From development to production
mRNA production involves DNA template preparation, in vitro transcription (IVT), mRNA modification, and DNA and protein removal steps. Our innovative solutions and custom services are designed to meet your specific quality, purity requirements, and scalable batch-to-batch consistency.
DNA template preparation in vitro
In vitro DNA templates can be produced using techniques such as rolling circle amplification (RCA) or PCR. RCA is a cell-free amplification method that is a promising alternative to traditional plasmid DNA and PCR amplification. RCA requires polymerases with strong displacement activity and dNTPs for strand synthesis; the reactions take place at constant temperature.
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| Phi29 DNA polymerase | EP0091 | TheraPure phi29 DNA Polymerase (10 U/μL) | - |
| dNTPs | dNTP Set, 100 mM Solutions | - | TheraPure GMP dNTPs |
Plasmid DNA linearization
Plasmid DNA is linearized with restriction enzyme, and the linearized DNA is then used as a template for in vitro transcription to produce mRNA.
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| Eam1104I restriction enzyme | Eam1104I (EarI) (10 U/μL) | TheraPure restriction enzymes | TheraPure GMP Eam1104I Restriction Enzyme, 20 U/μL |
mRNA transcription
During IVT reaction, the DNA template, RNA polymerase, NTPs, RNase inhibitor, pyrophosphatase, and IVT buffer are critical components for mRNA production.
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| T7 RNA polymerase | T7 RNA Polymerase, HC (200 U/μL) | TheraPure RNA polymerases | TheraPure GMP T7 RNA Polymerase, 200 U/μL |
| SP6 RNA polymerase | SP6 RNA Polymerase, HC (≥100 U/μL) | - | - |
| Ribonuclease inhibitor | RiboLock RNase Inhibitor (40 U/μL) | TheraPure modifying enzymes | TheraPure GMP RNase Inhibitor, 40 U/μL |
| Pyrophosphatase, inorganic | Pyrophosphatase, inorganic (0.1 U/μL) | TheraPure modifying enzymes | TheraPure GMP Pyrophosphatase, inorganic, 0.1 U/μL |
| NTPs | NTP Set, Tris buffered NTP Set, 100 mM Solution | TheraPure nucleotides | TheraPure GMP nucleotides |
| N1-Methylpseudo-UTP | Contact us | - | TheraPure GMP N1-Methylpseudo-UTP, 100 mM sodium solution |
| IVT buffer | Buffers for RNA transcription and post-transcriptional modifications | - | Contact us |
mRNA modification
Co-transcriptional or post-translational capping protects mRNA and promotes mRNA function. The poly-A tail addition stabilizes and prevents degradation of mRNA.
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| Vaccinia Capping Enzyme | Modifying enzymes | TheraPure Vaccinia Capping Enzyme, 100 U/µL | - |
| Vaccinia mRNA Cap 2'-O-Methyltransferase | Modifying enzymes | TheraPure 2'-O-Methyltransferase (125 U/μL) | - |
| S-Adenosyl-L-Methionine (SAM) | Co-factors | TheraPure S-Adenosyl-L-Methionine (32 mM) | Coming soon: TheraPure GMP S-Adenosyl-L-methionine, 32 mM |
| Poly A polymerase | Poly(A) Polymerase (cloned) 2 U/μL | - | - |
DNA template and protein removal
After IVT, the DNA template can be removed using DNAse enzyme. Proteinase K might be used for protein removal.
| Product | Standard | TheraPure | TheraPure GMP |
|---|---|---|---|
| DNAse I | DNase I, RNase-free, HC (50 U/μL) | TheraPure modifying enzymes | TheraPure GMP DNase I, RNase-free, 50 U/μL |
| Turbo DNAse | TURBO DNase (2 U/μL) | - | - |
| Proteinase K | Proteinase K, recombinant, PCR grade | - | - |
Product development and manufacturing capabilities
Technical expertise
50 years in enzyme and other reagent development have generated a substantial knowledge background that can be applied to further innovations.
Manufacturing
Our facilities are equipped to support high-scale product manufacturing. The animal origin-free and beta-lactam free facility operates under ISO 9001 and follows applicable ICH Q7 guidelines, ensuring the highest standards of quality and safety for TheraPure GMP products.
Quality
Implemented ISO9001 and/or ISO13485 quality management systems and extensive product testing ensures traceability, high product quality, and batch-to-batch consistency.
Supply chain
Different methods of transportation ensure smooth and safe product delivery directly to the customer or via a network of worldwide distribution centers.
Custom services for raw materials
Product customization
- ✓ Composition
- ✓ Volume
- ✓ Labeling
Quality
- ✓ Additional quality attributes
- ✓ Stability studies
- ✓ Shelf-life extension
New product development
- ✓ AOF product development
- ✓ GMP product development
- ✓ Your protein cloning, expression and purification
Featured products: Rolling circle amplification solutions
- The RCA method of isothermal amplification offers several advantages over traditional amplification methods, including faster performance, a cell-free process, a less complex protocol, and a lower risk of contamination. Explore RCA products for GMP mRNA production.
TheraPure GMP dNTPs
- High purity
- Manufactured following ICH Q7 GMP guidelines
- Validated production and QC process
* “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.
Stylesheet for Classic Wide Template adjustments