OVERVIEW OF mRNA MANUFACTURING FOR THERAPEUTIC DEVELOPMENT
Manufacturing mRNA requires significant expertise, equipment, and enterprise. Many steps are performed at the technical level to assemble a product that is more stable, less immunogenic, and better expressed in whatever cellular context it is used. The challenge of mRNA manufacturing means that a final product is sometimes produced by one company, two partnering companies, or multiple partners each with its own capabilities.
mRNA Manufacturing Process
STEP 1
Project design and process
development
development
• Sequence design
• Chemical modifications
• Purity and quality specs
• Quantity (scale-up) needs
STEP 2
Plasmid preparation
• Bioreactor fermentation
• Harvest, lysis
• Linearization
• Ultrafiltration/diafiltration
• Chromatographic purification
STEP 3
IN VITRO (IVT) SYNTHESIS OF mRNA
Post-transcriptional Capping
CO-TRANSCRIPTIONAL CAPPING
Added manual steps, hands-on time, and
manufacturing costs
Simplified workflow, reduced time, and
manufacturing costs
ivt synthesis reaction
PURIFICATION
- DNA, enzyme, NTP removal
- Chromatographic purification
- Flow filtration
IVT Synthesis Reaction +
Capping
- Methods: ARCA, CleanCap® reagent
- Only enzyme required is RNA
polymerase - Post IVT reaction modifications
possible
capping
- Method: Enzymatic
- Capping enzyme necessary
CleanCap technology gets you higher yield, lower immunogenicity, reduced timelines, and improved manufacturing process flow
VS
Post-transcriptional Capping
Added manual steps, hands-on time, and manufacturing costs
ivt synthesis reaction
PURIFICATION
• DNA, enzyme, NTP removal
• Chromatographic purification
• Flow filtration
capping
• Method: Enzymatic
• Capping enzyme necessary
VS
Co-transcriptional Capping
Simplified workflow, reduced time, and manufacturing costs
IVT Synthesis Reaction + Capping
• Methods: ARCA, CleanCap® reagent
• Only enzyme required is RNA polymerase
• Post IVT reaction modifications possible
CleanCap technology gets you higher yield, lower immunogenicity, reduced timelines, and improved manufacturing process flow
STEP 4
PURIFICATION
• DNA, enzyme, NTP removal
• Chromatographic purification
• Flow filtration
STEP 5
QA and QC Testing
• Mass spectrometry analytics
• NTP impurities
• Salt content
• Often custom, as needed
(OPTIONAL)
lnp encapsulation
purification
qc and testing
STEP 6
FILL AND FINISH
• Sterile filtration
• Aseptic filling
• Final quality check
STEP 7
SHIP
• Temperatures critical for stability
maintained throughout shipment
STEP 8
mRNA Manufacturing Permits
Therapeutic Innovation
Innovative mRNA products drive new
therapeutic development opportunities
therapeutic development opportunities
mRNA products available as substances
or drugs:
- mRNA substance: pure (only) active
pharmaceutical product - mRNA drug: mRNA therapeutics
supplied in their final formulation (e.g.,
LNP encapsulated)
mRNA Manufacturing Webinars
Jul 1, 2022