mRNA Drug Substance Production
As mRNA programs develop, quantity and quality requirements increase. Aldevron helps you advance to the next stage, where larger lot sizes, increasing levels of quality oversight and lot-to-lot consistency are required.
Aldevron produces high-quality mRNA to your specifications using scalable and processes capable of delivering milligram to multi-gram quantities. Aldevron can also provide high-quality enzymes and linearized plasmid DNA for your in-house mRNA synthesis requirements.
Synthesis with In Vitro Transcription (IVT)
We offer IVT enzymes that are qualified both by activity assays and functionally for RNA synthesis. Our IVT enzymes can also be custom manufactured to meet requirements for construct design and formulation in batch sizes ranging from milligram to multigram scale.
Capping/Tailing
Our flexible platform supports both enzymatic capping and co-capping. During development we study and optimize for nucleotides, reagents and enzymes mixture and process conditions (temp, and incubation period).
Purification
In the final stage of synthesis, the mRNA is purified in steps involving chromatography and ultrafiltration (UF)/diafiltration (DF) to prepare for the formulation stage.
QC Testing Panel
QC Testing
We provide comprehensive testing for critical attributes such as purity, identity, concentration, total residual protein content, residual DNA template, residual endotoxin content and bioburden. Based on the USP recommendations (released in March 2022) and other regulatory guidance, we are dedicated to meet the highest standard for RNA production and provide guidance to qualify material for our clients’ needs.
Table 1: Quality Attributes and Methods Used for mRNA Drug Substance
|
Quality Attribute |
Attribute |
Method |
|
Identity |
Sequence Confirmation |
RT-Sanger Sequencing |
|
Identity - UTR |
RT-PCR |
|
|
Content |
RNA Concentration |
UV (SoloVPE) |
|
Potency |
Activity Assay |
In vitro Transcription Assay |
|
Purity/ Integrity |
% Intact and fragment mRNA |
IP-RPLC, Fragment Analyzer |
|
5’ capping efficiency |
Malachite Green, UPLC, CE, BLI |
|
|
3’ poly(A) (% or length) |
UPLC, CE, BLI |
|
|
Impurity |
Product Related impurities – dsRNA |
Immunoblot, ELISA, BLI |
|
Process Related impurities - Residual Protein |
NanoOrangeTM, Cygnus HCP ELISA, process specific ELISA |
|
|
Process Related impurities - Residual Template |
qPCR |
|
|
Safety |
Endotoxin |
USP <85> Kinetic Chromogenic LAL |
|
Bioburden |
USP<61> |
Aldevron mRNA services provide scalability, raw material and process controls, raw material cost control and RG-to-GMP transferability, ensuring consistent quality and affordability. We also can support many of your project requirements for other reagents directly or indirectly tied to your mRNA portfolios with our complementary platform services and products.
Aldevron’s experts provide a depth of knowledge and breadth of expertise across the development, manufacturing, quality, regulatory and compliance landscapes. Our team has direct connections and first-hand experience, and will support you from start to finish, from idea to commercialization, to Clinical Trial or Investigational New Drug applications. We know what is needed to bring a new therapy to market and how to manufacture to the exact quality standards, at scale.
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