An integrated service, featuring an up to 300 L scale fermenter, ensures efficient mRNA transcription, purification, and state-of-the-art mRNA-LNP production with expertise and excellence in quality system. This platform covers all critical CMC processes, achieving a timeline of 8 months from DNA to IND filing.
Services for mRNA Products
Advancing mRNA Therapeutics and Vaccines from Sequence to IND
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WuXi Biologics offers extensive development capabilities and GMP manufacturing capacity for mRNA therapeutics and vaccines. Our expert and highly-trained team provides end-to-end services from early-stage development through to initial plasmid DNA manufacturing and on to drug substance (DS) and drug product (DP) GMP production. Our GMP services include a manufacturing facility with up to 300L scale fermenter for plasmid DNA production and 50L volume vessels and purification equipment for mRNA transcription and purification. In addition, state-of-the-art mRNA-LNP production systems and robotic aseptic filling systems are available for DP manufacturing. Like all of our services, the foundation of our mRNA service platform is built upon remarkable in-house, single-source CMC development and manufacturing capabilities and expertise, execution excellence, and our world-class quality system. TIPS: We also provide rapid material generation and high-quality feasibility study services as standalone projects.
WuXi Biologics’ services for mRNA therapeutics and vaccines
Integrated, End-to-end Services from Sequence to IND
Plasmid DNA manufacturing
E. coli strain construction
Plasmid purification
Plasmid DNA
Fermentation
In vitro transcription (Co-capping or post-capping)
mRNA transcription and purification
Key services include: Sequence optimization MCB/WCB creation and testing Process development:
Plasmid DNA linearized template
mRNA purification
mRNA DS
mRNA-LNP formulation
Sterile filtration
LNP encapsulation
TFF
mRNA-LNP
Plasmid DNA: E. coli fermentation, cell lysis and purification mRNA: In Vitro Transcription (IVT) including co-capping or post-capping, purification LNP: encapsulation, UF/DF, fill/finish
DS & DP manufacturing
Stability
mRNA DS
mRNA-LNP
Release
Tech transfer and scale-up GMP manufacturing: DS and DP Comprehensive analytical development and QC testing capability Full CMC and regulatory support
WuXi Biologics services cover all critical CMC processes with a timeline of 8 months from DNA to IND filing.
8 months from DNA to IND filing
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Tox materials release
GMP pDNA release
DNA
GMP mRNA release
GMP mRNA-LNP DP release
Drug Substance
Our GMP services include a manufacturing facility with up to 300 L scale fermenter for plasmid DNA production and various volume vessels and purification equipment for mRNA transcription and purification.
For Sequence to Cell Bank
mRNA DS suite #1
Sequence synthesis
Sequence synthesis in 2-4 weeks; codon optimization
Vector construction
A matrix of vector backbones with different UTRs, polyA, restriction sites, etc.
Strain & clone screening
E. coli strain and clone screening for stable and high production of plasmid DNA
Bacterial cell banking
PD & GMP cell banking; cell bank release and testing
WuXi Biologics provides a matrix of vector backbones with different designs of promoters, UTRs, polyA, restriction sites, etc.
mRNA DS suite #2
mRNA Production Process
pDNA linearization
• Selection of restriction enzyme • Optimization of reagent concentration and reaction condition to ensure complete linearization
GMP plasmid DNA intermediate production • State-of-the-art GMP suites • Multiple single-use fermenters up to 300 L • Platform process with high yield
Purification of linearized pDNA
in vitro transcription
• With or without cap analogs • Optimization of reagent concentration and reaction conditions to achieve high yield of mRNA & complete digestion of pDNA template
GMP drug substance
mRNA recovery*
• One suite of pDNA linearization • One suite of mRNA synthesis • One purification suite for mRNA, with extensive utilization of advanced single use technology
Enzymatic capping*
• Optimization of reagent concentration and reaction conditions to achieve high capping efficiency and minimize enzyme cost
mRNA purification
*Not required for co-transciptional capping
Drug Product
Drug Product Manufacturing
Our DP offerings include state-of-the-art mRNA-LNP production systems as well as robotic aseptic filling systems.
• Two segregated Vanrx SA25 Robotic filling lines • Microfluidic and T-junction encapsulation processes • Aseptic formulation isolator • Single-use systems • Ready-to-use container-closure systems (vials and pre-filled syringes)
Drug Product Development
• Microfluidic and T-Junction mixing technologies • Formulation development, process development and technology transfer • Lyophilization cycle development • Stability, stress study, CCIT, clinical in-use study • 25 µL to 10 L scale (feasibility / pilot) • Extensive mRNA-LNP DP characterization techniques: particle size, PDI, encapsulation rate, potency, etc.
From sequence to LNP for all mRNA programs
Flexible dosage forms: liquid and frozen vials, freeze-dried vials and pre-filled syringes
Microfluidic Mixing Technology
Impingement Jets Mixing Technology
0.6 m 2 freeze-dryer equipped with AI software and nucleation control technology
Analytical Science and Quality Control
• Comprehensive analytical capabilities for full CMC packages that enable IND/BLA filings • Tox/Clinical lot DS/DP release and stability testing • Reference standard generation, qualification, characterization, storage, and life-time management • Analytical investigation/troubleshooting for GMP manufacturing related issues
Our dedicated team of highly trained and experienced analytical and QC professionals, allows us to offer: • Integrated labs that support diverse mRNA modalities • Methods development, transfer and qualification/validation • Product biochemical, biophysical, and biological characterization and comparability analysis
Identity
Purity
Impurity
Potency
Safety
pDNA supercoiled% A260/280 by UV absorbance
pDNA sequencing Restriction enzyme digestion
pDNA
Residual dsRNA Residual host cell protein by ELISA Residual host cell DNA Residual solvent Residual antibiotics Residual DNA template
S terility Bioburden Mycoplasma Endotoxin
RNA integrity and fragment Capping efficiency polyA tail length Encapsulation efficiency LNP size and zeta potential LNP morphology
In vitro GOI expression by Cell-based Assay(CBA)
RNA length RNA sequencing
RNA
RNA-LNP
Lipid identification
• Document management/ training • Deviation/CC/CAPA • Quality agreement management • Management review
• Batch release • Warehouse management • Product reception, storage, and distribution • Handling of abnormal and nonconforming materials and products • Supplier management
Quality Assurance System
• Internal audit • Batch release
• Sample management • Retained sample management • Reference standard management • Stability management • Environmental monitoring • Contamination and cross- contamination control strategy • DS/DP production technique transfer • Risk assessment of NPI • Clearance and changeover • Cleaning and disinfection
• Calibration and maintenance • Pest control • Validation management • Water system/HVAC
• Distribution and control of label
About WuXi Biologics
WuXi Biologics is a leading contract research, development and manufacturing organization (CRDMO) that provides end-to-end capabilities to healthcare organizations worldwide. With operations in China, the United States, Ireland, Germany, and Singapore, we enable our partners to effectively and efficiently bring biologics and vaccines to patients worldwide through our comprehensive and high-quality drug development model.
wuxibiologics.com | info@wuxibiologics.com The world’s leading global single-source platform from concept to commercialization.
5-12-2023
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