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Plasmid DNA in Cell and Gene Therapy: From Bench to Bedside
James Brown, Ph.D. Aldevron
Plasmid DNA in Cell and Gene Therapy: From Bench to Bedside James - - PowerPoint PPT Presentation
Plasmid DNA in Cell and Gene Therapy: From Bench to Bedside James - - PowerPoint PPT Presentation
Plasmid DNA in Cell and Gene Therapy: From Bench to Bedside James Brown, Ph.D. Aldevron Getting from here to there bench-to-bedside - A term used to describe the process by which the results of research done in the laboratory are directly used
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What are the options? When do I use them? How do I move faster?
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What’s the difference?
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More alike than different…
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What are the differences? Additional standard tests
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What are the differences? Additional optional tests
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What are the differences? QC service level
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What are the differences? Production service level
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Basic process is the same
Transformation Growth Harvest Lysis Chromatography Diafiltration Quality Control
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What are the differences? Scale and environment
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What are the differences? In-process QC
Transformation Growth Harvest Lysis Chromatography Diafiltration Quality Control
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What are the differences? Facilities
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What are the differences? Facility monitoring
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…inside
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…inside
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Consideration on the path from bench to bedside
Complexity of material Stage of Development Proximity to patient
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Complexity of material
Increasing Complexity Small Molecules Nucleic Acids Proteins Enzymes Antibodies Live cells Viral vector
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Stages of Development
Increased quality oversight, process control, and environmental control for ancillary/raw material manufacturing Consistent manufacturing process Consistent specifications Ability to scale up and out
http://www.ipmglobal.org/sites/default/files/Stages-Clinical-Trials2.png
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Proximity to patient
Bacterial cell bank Plasmid DNA “Complexed” DNA
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Proximity to patient
Bacterial cell bank Plasmid DNA Bacterial cell bank IVT Enzymes mRNA
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Proximity to patient
Bacterial cell bank Plasmid DNA Bacterial cell bank IVT Enzymes mRNA Transduced cell
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Proximity to patient
Bacterial cell bank Plasmid DNA Mammalian cell bank Viral vector
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Proximity to patient
Bacterial cell bank Mammalian cell bank Viral vector Plasmid DNA Transduced cell
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This is the direction Congress gave the FDA by creating vehicles like the accelerated approval pathway. How do we move even faster?
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Taken together these results could be used to substantiate a reduced SC specification for a pDNA vaccine. SC and OC isoforms were shown to be competent at directing target gene expression in vitro using both lipid mediated transfection and electroporation
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Should we cut corners?
No! Risk assessment of options based on sound scientific principles and data.
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Scale up, increase throughput
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Scale out, personalized gene therapy
http://clincancerres.aacrjournals.org/content/22/4/807
Patient 1 Patient 2 Patient 3 Patient 4 Patient n …
Development of parallel processing, closed systems Short TAT, on the order of weeks
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Immediate availability of critical components
pALD-X80 Cas9
sv40 NLS
SpyFi™ Cas9
sv40 NLS sv40 NLS
SpCas9
sv40 NLS sv40 NLS
SpCas9
sv40 NLS Myc His HA Nuc. NLS sv40 NLS
AsCpf1
sv40 NLS
Off-the-shelf research and GMP/S products reduce timelines
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Improve production processes
Single-Use Equipment Reduce Product Carryover
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The noblest art is that of making others hap happy.
- P. T. Barnum