Recommended
Recommended
More Related Content
Similar to COMPACT mRNA PRODUCTION THROUGH PROCESS INTENSIFICATION AND INNOVATION
Similar to COMPACT mRNA PRODUCTION THROUGH PROCESS INTENSIFICATION AND INNOVATION (20)
More from iQHub
More from iQHub (20)
Recently uploaded
Recently uploaded (20)
COMPACT mRNA PRODUCTION THROUGH PROCESS INTENSIFICATION AND INNOVATION
- 1. GREATER ACCESS & AUTONOMY through innovation in bioproduction Confidential presentation Vaccine Technology Summit 2023 Cambridge, MA 20 MARCH 2022 Compact mRNA Production through Process Intensification & Innovation
- 3. 3 Conventional mRNA production: uniformity in variety https://doi.org/10.3390/biomedicines10010050 DOI: 10.13140/RG.2.2.34118.80966 https://repository.upenn.edu/cbe_sdr/132 https://doi.org/10.1016/j.trsl.2021.11.009 https://doi.org/10.1021/acs.iecr.2c01217
- 4. 4 Conventional mRNA production: uniformity in variety n INCUBATION TFF CHROMATOGRAPHY TFF • Facility footprint • Acquisition of individual production systems: – Investment – Need for installation, commissioning, qualification of each – Available equipment scales vs. (GMP!) process needs? PROCESS INFRASTRUCTURE • Batch operation: system idle time, transfer of intermediates between unit steps (➜ process hold, operator intervention, increased total process duration…) • Several UF / DF operations ➜ volume of TFF buffers, process waste • Cumulative loss of material over DSP = decrease in yield PROCESS OPERATION PROCESS SUPPLY • Long bill of materials: complex supply chain management, vendor qualification & control, QC requirements • Many suppliers = many failure points PROCESS DEVELOPMENT • Development of custom or generic (“template”) mRNA process • Process optimization, characterization, qualification - including mixing of process solutions, storage of prepared solutions and intermediates, chromatography resin lifetime studies… • Process scale-up from R&D to mass scale INCUBATION CHROMATOGRAPHY TFF Implications
- 6. 6 Building Ntensify™ the start of the Nfinity™ platform
- 7. 7 In partnership with Width System: 2065 mm Height System: 2400 mm Width Chamber Opening: 1950 mm Height Chamber Opening: 600 mm User Interface: 560 mm Depth System: 786 mm Batch Size: up to ~5 g (~ 12 h operation) Weight: 840 kg LAF Flow Rate: 0.45 m/s Integrated Particle Counter
- 8. 8 USP DSP
- 9. 9
- 10. 10
- 11. 11
- 12. 12 The power of process intensification and innovation GMP 1 3 Upgrade Mini Maxi Midi 2 R&D • Optimized, generic process • Ready-to-use reaction mixes • No scale-up (scale-out / scale-in-time) • One fully automated, integrated system • Easy installation • Limited facility impact (small Grade D / ISO 8 room) • Lower COGS
- 13. 13 Our upstream process consistently delivers a high yield of capped mRNA transcripts and low impurity levels… YIELD Reactions: 245 Constructs: 45 4.0 7.2 CAPPING EFFICIENCY Reactions: 111 Constructs: 19 87.5 97.9
- 14. 14 Our upstream process consistently delivers a high yield of capped mRNA transcripts and low impurity levels… RESIDUAL DNA Reactions: 39 Constructs: 6 0.03 29.5 dsRNA CONTENT Reactions: UTP: 83; mUTP: 36 Constructs: UTP: 36; mUTP: 31 38.9 397.4 75.8 727.0
- 15. 15 Our upstream process consistently delivers a high yield of capped mRNA transcripts and low impurity levels… 1166 bases 4284 bases 1999 bases 2080 bases 3979 bases 4060 bases
- 16. 16 … requiring minimal downstream processing with minimal product losses 73.5 106.1 YIELD Runs: 28 | Constructs: 3 0.82 1.09 INTEGRITY (PRE/POST) Runs: 22 | Constructs: 3 0.2 1.1 RESIDUAL PROTEIN Runs: 19 | Constructs: 3
- 17. 17 What’s NEXT?
- 18. 18 Quantoom’s Nfinity™ platform: from sequence to formulation NfinityTM Platform RNA Synthesis RNA Purification Encapsulation & Formulation DNA Linear DNA Fill & Finish Nplify Ntensify Ncapsulate mRNA Workflow
- 19. THANK YOU for your attention! 19