5/15/17
4th ANNUAL BIO-MANUFACTURING SUMMIT June 7th - 8th 2017 Miami, Florida BRIDGING THE GAP BETWEEN BUSINESS, TECHNOLOGY AND SCIENCE TO OPTIMIZE BIOPROCESSING Sarfaraz K. Niazi, Ph.D. Adjunct Professor, University of Illinois
Bioinnovation: Cost and Time Optimized Development of Biosimilars 2
Niazi, largest solo biotech inventor
Cost & Time Drivers for Biosimilars • New Reality • Commercial scale (GMP) lots for testing • Structural variance within reference variance • Side by side stability testing with reference
• Drivers • DOE • Facility dedication • Scale up
Downstream
Capture
Filtration
• Float column, resin puck, modular • Multiple resins • Lossless
• Nonspecific, In situ • Protein, metabolites • Customized
• Non-blocking • Air-scrubbed • Built-in
Upstream
Mixing
Contamination
• Unstirred, convective • Horizontal, bed sparge • Noninvasive Monitor
• Unstirred • Levitating • Gravitational
• Single-pass HVAC • Virus Removal • Filter-free Exhaust
Source: www.worldwide.escapenet.com Approximately 127 results found in the Worldwide database for txt = sarfaraz and txt = niazi 3
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Key Invention Categories • Base:
• Horizontal, single-use, free-standing pillow, orbital motion, short dwell time, DOE
• ISO 9 operable:
• Patented ports, filter-free exhaust, recirculation, burn off
Winner: Innovation of the Year
• Convective heat transfer:
• Cell shock, instant cycling, improved PTMs
• Harvesting first:
• No centrifugation and filtration
• Continuous and Perfusion:
One of the fastest patents ever issued by USPTO
• Non-blocking filter, gravity driven, point of expession capture
• Scale up and tech transfer:
• Pooling, geometric mixing, no comparability protocol
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More Than a Bioreactor
• • • • • • • • •
Pillow, un-walled Convective heat Capture first Perfusion, continuous ISO9 Full bed gassing Short-dwell, PTMs DOE Tech transfer
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Managing At Scale Requirement
Perfusion
• Closed system • Gravity drive • No strain on cells and protein—no pump • Continuous or end of cycle • Cell or cell and protein separation • No contamination
• Modular upstream: CFR 21 compliant. • One size validated—no scaling up • Combining multiple sources of upstream without using larger container, geometric dilution, contamination-proof system
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Continuous Bioreactor
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Single Container Manufacturing • Removes three major steps—time and cost • Improves yield • Direct capture, washing, elution • Improves quality of product • Conserves resin cost
• Expansion-production • Gravity-cell strain • Perpetual cycle • Continuous harvest • Universal cell lines
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Single Use Downstream Purification
Non-blocking Filtration
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• Air/liquid drive scrubbing of filter surface • Solid ceramic filters permanently installed • Eliminates depth filtration, paper filter and use of pressure filtration • Disposed and sterilized inside bioreactor • Global use of slurry treatment
• Stacked discs reclaim resin • Multiple columns combined in one • Custom configurations • High yield • No column packing • All parts single use • Float Column
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Facility
Non-invasive Monitoring • No sensors in contact with media • No interference due to chemical reaction • Cuvette in liquid concept • Allows expensive sensors—not disposable
• • • •
• Cost effective • Readily validated
Single-pass low loss HVAC Maximum energy recovery Each area individually classified Viral clearance: air scrubbing
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Cost & Time Drivers Managed
Exhaust Control • Recycle exhaust, replenish nutrition gas • Condenser reflux, venture effect • Bunsen burner with added oxygen • Connected to outside • One-way outlet for pressure changes • Positive pressure in container
• Create one small size scale: multiply rather than increase size • Operate in a ISO9 facility • Use horizontal bioreactor for PTM and variation management • Use same bioreactor for DOE and Commercial manufacturing • Develop multiple products simultaneously • Eliminate cell culture separation and reduce depth filtration volume • Single-use upstream and downstream • Enclosed perfusion and continuous manufacturing • Minimize Comparability Protocol constraints 17
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New Tech New Challenges Considerations
Examples Recombinant Proteins Organs Fine Chemicals Energy Sources
New Products
• • • •
New Expression Systems
• Bacteria, Mammalian Cells • Plant and insect Cells, Yeast • Multiple Expressions Lines
Regulatory Compliance Commercial Manufacturing
• Cleaning Validation, CrossContamination, Viral Clearance • Regulatory Expectations • Scale-Up, Portability, point of use • Technology Transfer • Continuous Yield, Single container Utilities, Ceiling Height ISO9, Foot-Print, Size Qualification, COGS Continuous yield Hardware
Capital Cost
• • • • •
Development Cost
• Fast to the market possibility
Key Questions Is there a universal platform for all products?
Is there a universal bioreactor for all expression systems? Is there a safe, contamination-resistant bioreactor? Is there a scale-up and tech-transfer-friendly platform?
Is there a cost-effective bioreactor suitable for all business type?
Is there a bioreactor for fast-to-market capability? 19
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