Presentation is loading. Please wait.

Presentation is loading. Please wait.

James Robinson, PE Vice President, Technical & Quality Operations

Similar presentations


Presentation on theme: "James Robinson, PE Vice President, Technical & Quality Operations"— Presentation transcript:

1 Disposable Manufacturing System for Rapid Mass Production of Influenza Vaccine
James Robinson, PE Vice President, Technical & Quality Operations Novavax, Inc. Bob Bader Senior Manager Technology - Pharma Bio Jacobs Engineering March 26-28, 2008 Pennsylvania Convention Center

2 Influenza Vaccine Manufacturing Today
Agenda Today’s Flu Vaccines The ‘Ideal’ Flu Vaccine Virus-Like Particle Flu Vaccine in Insect Cells Advantages of VLP Vaccine Manufacturing Economic Impact of Disposable Manufacturing Systems in Influenza Manufacturing Summary

3 Influenza Vaccine Manufacturing Today
US Licensed Inactivated influenza vaccines Whole virion Split virion Live-attenuated vaccines Approaching Licensure Adjuvanted inactivated vaccines* Recombinant HA vaccine In Development Virus-Like Particles DNA Vaccines Universal Flu Vaccines *some licensed in EU

4 Influenza Vaccine Manufacturing Today
Vast majority (>90%) of licensed capacity is in egg-based products Reliable process for seasonal production Potential loss of supply in an avian flu outbreak First cell culture facilities are coming on line in Europe Significant investment in new US facilities continues Egg ($1.5 capital/dose capacity) and cell-culture ($3/dose) Demand promises to grow with supply Expanded recommendations Pandemic preparedness Market shortages globally

5 Pandemic Influenza Vaccine Manufacturing Challenges
Non-adjuvanted pandemic vaccines to date have required increased doses for a protective HAI response Yield of pandemic vaccine production in eggs is lower than seasonal strains The likelihood of a pandemic event is driving increased capacity and advances in flu technology Risk of overcapacity for seasonal markets The time required to obtain high-producing non-pathogenic strains challenges a fast delivery of pandemic vaccine once a pandemic is declared Virus mutations could greatly reduce the value of the vaccine stockpiles created.

6 Influenza Vaccine Manufacturing Tomorrow
Vaccine supply that does not rely on egg-based production High yielding process supporting a robust response with less investment Fast response to an emerging influenza strain Cross-protective product for antigenic drift Flexible facility that supports other products when not producing for a pandemic threat Rapid scale-up Improved stability Available regionally +/- +/-

7 Influenza Vaccine Manufacturing in Insect Cells
Novavax, Inc. is developing an Influenza Virus-Like Particle (VLP) Vaccine as an alternative to traditional influenza vaccines The process uses recombinant baculovirus to infect and express VLPs that contain Hemagglutinin (HA), Neuraminidase (NA), and Matrix (M1) Protein The proteins self-assemble as particles that resemble influenza virus, but do not contain flu RNA The approach has a number of quality and manufacturing advantages to the traditional influenza manufacturing processes

8 Cryo-electron Microscopy of Pleomorphic VLPs
A/Indo H5N1 VLPs

9 Why Recombinant Influenza VLP Vaccine
Speed from strain selection to product release is weeks Exact genetic match Recombinant VLP’s are clinically proven (HPV, HBsAg) with a broad immune response Improved immunogenicity of flu VLPs (vs. split virion vaccine) in preclinical studies No eggs Yields are higher than egg-based production; potential for additional increase in yield No pathogenic virus in manufacturing Controlled cell culture process (Serum-free, Protein-free, Suspension Culture) The use of this approach has allowed Novavax, Inc to develop a process that uses disposable equipment and closed systems for product processing

10 Faster Delivery of First Dose
9+ week advantage Product Availability Cloning & Seed Prep Mfg & Fill 1st Lot Release & Ship NOVAVAX 4 wks 8 wks 12 wks 16 wks 20 wks 24 wks 28 wks Traditional RG pathogenicity Mfg Wait for Reagents Form/Fill, Release & Ship sequence available

11 Influenza Vaccine Production
Cell Substrate Preparation Remove Cells, Purify Virus Infect & Incubate Inactivate Virus Traditional Flu Vaccine Production*: Grow, Collect, & Fertilize Eggs LS/HS Centrifugation, Diafiltration, Chromatography Treat with Formaldehyde (subvirion products treated with detergent) Infect with Influenza Virus Incubate Thaw vial from WCB Grow to Mfg Scale Insect Cell Culture-Based Flu Vaccine Production: Infect with Recombinant Baculovirus, Incubate Thaw vial from WCB Grow to Mfg Scale MF/DF, Chromatography baculovirus inactivated

12 Influenza Vaccine Production
Cell Substrate Preparation Remove Cells, Purify Virus Infect & Incubate Inactivate Virus Traditional Flu Vaccine Production*: Infect Incubate Candle Chill Harvest Insect Cell Culture-Based Flu Vaccine Production:

13 Influenza Vaccine Production
Cell Substrate Preparation Remove Cells, Purify Virus Infect & Incubate Inactivate Virus Traditional Flu Vaccine Production*: Insect Cell Culture-Based Flu Vaccine Production:

14 Influenza Vaccine Production
Relative Influenza Process Yield egg based current insect cell process Relative Yield (Doses/L) cell-based 15 30 45 90 mcg/dose

15 Influenza Vaccine Production
Process Equipment Comparison Process Egg Based Insect Cell Culture Upstream Custom Inoculators Single Use Bioreactors Large Incubators Candling Stations Custom Harvesters Purification Large Fixed Tanks Single Use Bags Low Speed Centrifuges Single Use Microfiltration Filtration Ultrafiltration Skids Single Use Ultrafiltration Ultra Centrifuges Chromatography Buffer Prep Single Use Buffer Prep Buffer Storage Buffer Bags Sub-micron Filtration Single Use Sub-micron Filters

16 Influenza Vaccine Production
Support Equipment Comparison Support Egg Based Insect Cell Culture Process Large WFI System Small WFI System CIP Skids (Multiple) N/A Clean Steam/SIP Systems Egg Disposal System Autoclaves Parts Washers Containment Decon Autoclave Large Liquid Waste Kill System Small Liquid Waste Kill System BL2+ Facility Design GLSP Facility Design Class B HVAC Systems Class C HVAC Systems

17 Influenza Vaccine Production
Traditional Flu Vaccine Production Capital Costs: egg-based facility USA 100M doses/year (600K eggs/day) 140K square feet $150M mammalian cell culture facility USA 100M doses/year 140K square feet $300M Insect Cell Culture-Based Flu Vaccine Production: Novavax, Inc Insect Cell Culture Rockville, MD Disposable Approach 75M doses/year 55K square feet $40M Benchmark cell culture facility 2 – 5,000L reactors Traditional Approach Fully automated downstream $225M

18 Influenza Vaccine Production
Comparison of Project Duration Time, yrs 1 2 3 4 Design Construction Commissioning Qualification Validation Egg Based Process Insect Cell Culture Time Saved

19 Influenza Vaccine Production
Comparison of Project Duration Time, yrs 1 2 3 4 Design Construction Commissioning Qualification Validation Egg- Based Process Insect Cell Culture Time Saved Earlier Revenue Generation Faster Payback on Smaller Investment

20 Utility Comparison 1.0 Egg Based Egg Based 49% VLP 8% 0.0 Process
Building Utilities Process Utilities

21 Influenza Vaccine Production
Traditional Flu Vaccine Production Unit Costs: Relative Variable costs Relative Fixed costs Egg-based materials labor depreciation utilities Mammalian cell culture materials labor depreciation utilities Insect Cell Culture-Based Flu Vaccine Production Unit Costs: Relative Variable costs Relative Fixed costs materials labor depreciation utilities COGS = unit variable costs + fixed costs units made Lower fixed cost reduces dependence on production volume for low unit cost. Higher yields drive lower variable costs.

22 Influenza Vaccine Production The Disposable Approach
Advantages of Disposable/Closed Manufacturing Approach Reduced process equipment complexity Reduced facility complexity and cost Faster Construction, Commissioning, and Launch Rapid expansion of capacity No change-over cleaning/validation between strains/products LEAN manufacturing approach Significant reduction in facility/equipment validation (>50%) Manufacturing cost structure shifted to variable costs Significant reduction in capital equipment costs (>70%) Supports a regional manufacturing approach

23 Influenza Vaccine Production The Disposable Approach
Traditional Flu Vaccine Production: Large, central manufacturing facilities Located in developed countries Supported by complex site infrastructure ~100M doses $150 – $300M Egg Based Facility $150,000,000 Sq ft 145,000 Insect Cell Culture-Based Flu Vaccine Production: Facilities Distributed Globally Located where vaccine is needed Requiring little local infrastructure 10 – 20 M doses (75M dose plant for ~$40M) NVAX VLPs Facility $40,000,000 Sq ft 55,000

24 Influenza Vaccine Production The Disposable Approach
Summary Production of Recombinant Influenza VLP Vaccine offers a favorable alternative to traditional manufacturing approaches The elimination of the pathogenic virus in the manufacturing process eliminates containment concerns and allows use of disposable systems Disposable systems provide significant economic benefits to influenza manufacturing Lower Capital Cost Faster Facility Start-up Rapid Expansion of Capacity Faster Investment Payback These benefits are well aligned with the needs of a global influenza solution for pandemic and seasonal disease


Download ppt "James Robinson, PE Vice President, Technical & Quality Operations"

Similar presentations


Ads by Google