Economic Impact of Single-Use Bioreactors

Transcription

1 Economic Impact of Single-Use Bioreactors Rick Stock 2012 BIO International Convention BioProcess Theater Presentation Upstream Processing Boston, MA June 19th, 2012 BioProcess Technology Consultants

2 Current Facility Designs Large hard-piped, stainless steel based facilities with stainless steel bioreactors Very expensive to build and validate Construction costs $300 Million Construction timelines 2-5 years or more Controlled environment, highly classified suites Tightly controlled flow of people, materials, and equipment Huge utilities for WFI, HVAC, clean steam, CIP Extensive piping, transfer panels, complex operations Photos courtesy of Lonza Biologics From Clone to Commercial

3 Today s Biopharmaceutical Facility Most facilities today were built for low titer (<1 g/l) processes Multiple 20,000 L bioreactors each with inoculum bioreactors up to 4,000 L Current facilities struggle to match downstream capacity with bioreactor output due to large process volumes Technologies that enable higher bioreactor titers will exasperate the DSP bottleneck Photos courtesy of Lonza Biologics From Clone to Commercial

4 Innovation has Increased Titers and Yields 1978 Recombinant insulin produced 2010 Commercial products have expression levels in the range of g/l with the highest titers seen for monoclonal antibody products Industry Standard: 1-3 g/l Industry Leaders: 3-8 g/l Improved strains New technologies to improve cell line development and expression levels coupled with improved and optimized media, supplements, and bioreactor conditions have increased titers Future Leaders: >10 g/l Ref: T. Charlebois, BIOMAN 2006 Conference, (2006); M. Smith, BPI Europe Conference (2005); F. Wurm, Nature Biotechnology, (2004) From Clone to Commercial

5 A Brief History of Single-Use Bioreactors 1970s Use of flasks, pipettes, filters, blood bags 1996 Introduction of Wave Bioreactor 2004 First 250 L disposable bioreactor 1980s Bags for media, harvest, buffer prep 2009 First 2,000 L disposable bioreactor From Clone to Commercial

6 Single Use Bioreactors Xcellerex XDR TM Bioreactor Sartorius Stedim Biostat Culti-bag Thermo Fisher (Hyclone) Single-use Bioreactor GE Healthcare Wave Bioreactor ATMI Nucleo TM Bioreactor From Clone to Commercial

7 Stainless Steel vs. Single-use Bioreactors (% ) Aggregate (%) Acidic Isoforms Main Peak 0 Monomer Total Agg 1000L SUB BR 100L SS BR 3L BR 1000L SUB BR 100L SS BR 3L BR Comparable cell growth and productivity Product yield and quality similar in both systems Ref: Noe, W, Antibody Development and Production (2011) From Clone to Commercial

8 Environmental Impact of Disposables Energy Consumption Water Usage Reduced water usage of up to 183,000 L/batch at 1,000 L scale Compared to cleanable stainless steel systems, single use systems use: 8 20X less water and cleaning chemicals Approximately 50% less energy consumption Ref: Sinclair A, et al. BioPharm Int. (2008), Rawlings B, Pora H. BioProcess Int. (2009), Noe, W, Antibody Development and Production (2011) From Clone to Commercial

9 Driving Forces for Single-Use Technologies Improved return on capital Reduced and deferred capital investment Increased speed of deployment Cost structure shifted to variable costs (reduction in capital equipment costs) Greater flexibility to match bioreactor size with titers and needs Reduced process equipment complexity Process and product flexibility Improved process control and portability Reduced facility complexity and cost Faster construction, commissioning, and launch No change-over cleaning/validation between strains/products Significant reduction in facility/equipment validation From Clone to Commercial

10 Modeled Monoclonal Antibody Process Seed 1 Seed 2 Seed 3 Production Centrifugation Depth Filtration UF/DF 1 Protein A Viral Inactivation Cation Exchange Anion Exchange Viral Filtration UF/DF 2 Final Filtration Fill/Finish 10 From Clone to Clinic

11 Process Case #1 Monoclonal Antibody Production Designed for monoclonal antibody product with expression levels of 2 g/l and 5g/L with a 66% overall purification yield (filled vial) 2,000L Scale Disposables used for media & buffer prep and product holds (<2,000L) Single product facility Single reactor Single purification line Batch duration: ~8 weeks including change over times ~4 weeks inoculum train (3 seed steps) ~2 weeks bioreactor (bottle neck) ~1 week purification ~0.5 week final purification and bulk filling 150 mg dose (liquid fill) in a 25 ml vial From Clone to Commercial

12 Process Case #1A 2,000L Case, 2 g/l Traditional SS Single-Use % Difference # of Batches/year % Throughput (kg/year) % Total Capital % Total Annual Costs $20,670,000 $20,800,000 +1% Capital Charge $6,460,000 $6,080,000-6% Materials $740,000 $870, % Consumables $2,470,000 $3,510, % Labor (Direct/Indirect) $9,090,000 $8,560,000-6% Maintenance/Utilities $1,930,000 $1,810,000-6% COGS ($/g) $414 $344-17% 12 From Clone to Clinic

13 Process Case #1B 2,000L Case, 5 g/l Traditional SS Single-Use % Difference # of Batches/year % Throughput (kg/year) % Total Capital % Total Annual Costs $25,140,000 $25,690,000 +2% Capital Charge $8,130,000 $7,730,000-5% Materials $820,000 $970, % Consumables $4,230,000 $5,590, % Labor (Direct/Indirect) $9,550,000 $9,100,000-5% Maintenance/Utilities $2,440,000 $2,320,000-5% COGS ($/g) $201 $170-16% 13 From Clone to Clinic

14 Process Case #2 Monoclonal Antibody Production Designed for monoclonal antibody product with expression levels of 2 g/l and 5g/L with a 66% overall purification yield (filled vial) 10,000L Scale: 5 x 2000L Disposable vs 2 x 5,000L Traditional SS Disposables used for media & buffer prep and product holds (<2,000L) Single product facility Single purification line Pool 2 of the disposable runs Batch duration: ~8 weeks including change over times ~4 weeks inoculum train (3 seed steps) ~2 weeks bioreactor (bottle neck) ~1 week purification ~0.5 week final purification and bulk filling 150 mg dose (liquid fill) in a 25 ml vial From Clone to Commercial

15 Process Case #2A 10,000L Case, 2 g/l, Single Product Traditional SS Single-Use % Difference # Equiv. of Batches/year % Throughput (kg/year) % Total Capital % Total Annual Costs $53,150,000 $55,690,000 +5% Capital Charge $17,080,000 $13,290,000-22% Materials $2,780,000 $3,380, % Consumables $8,470,000 $12,350, % Labor (Direct/Indirect) $19,660,000 $22,640, % Maintenance/Utilities $5,190,000 $4,060,000-22% COGS ($/g) $207 $183-12% 15 From Clone to Clinic

16 Process Case #2B 10,000L Case, 5 g/l, Single Product Traditional SS Single-Use % Difference # Equiv. of Batches/year % Throughput (kg/year) % Total Capital % Total Annual Costs $62,280,000 $67,310,000 +8% Capital Charge $18,970,000 $14,400,000-24% Materials $3,040,000 $3,760, % Consumables $12,010,000 $18,470, % Labor (Direct/Indirect) $22,470,000 $26,200, % Maintenance/Utilities $5,820,000 $4,500,000-23% COGS ($/g) $97 $88-9% 16 From Clone to Clinic

17 Process Case #3 Monoclonal Antibody Production Designed for monoclonal antibody product with expression levels of 2 g/l and 5g/L with a 66% overall purification yield (filled vial) 10,000L Scale: 5 x 2000L Disposable vs 2 x 5,000L Traditional SS Disposables used for media & buffer prep and product holds (<2,000L) Multi-product product facility, 4 products/year, 2 campaigns each Two purification lines Batch duration: ~8 weeks including change over times ~4 weeks inoculum train (3 seed steps) ~2 weeks bioreactor (bottle neck) ~1 week purification ~0.5 week final purification and bulk filling 150 mg dose (liquid fill) in a 25 ml vial From Clone to Commercial

18 Process Case #3A 10,000L Case, 2 g/l, Multi-Product Traditional SS Single-Use % Difference # Equiv. of Batches/year % Throughput (kg/year) % Total Capital ($M) $103.1 $ % Total Annual Costs $46,680,000 $53,050, % Capital Charge $17,080,000 $13,290,000-22% Materials $2,180,000 $3,220, % Consumables $6,660,000 $11,750, % Labor (Direct/Indirect) $15,640,000 $21,650, % Maintenance/Utilities $5,150,000 $4,050,000-21% COGS ($/g) $229 $183-20% 18 From Clone to Clinic

19 Process Case #3B 10,000L Case, 5 g/l, Multi-Product Traditional SS Single-Use % Difference # Equiv. of Batches/year % Throughput (kg/year) % Total Capital % Total Annual Costs $54,270,000 $65,140, % Capital Charge $18,970,000 $14,400,000-24% Materials $2,390,000 $3,580, % Consumables $9,430,000 $17,580, % Labor (Direct/Indirect) $17,740,000 $25,120, % Maintenance/Utilities $5,760,000 $4,490,000-22% COGS ($/g) $107 $89-17% 19 From Clone to Clinic

20 Summary/Conclusions Greatest impact is on efficiency and flexibility Allows for greater throughput (more batches) which lowers cost of goods Single-use bioreactors can have higher operating costs on a yearly basis Higher operating costs are due to increase in batch capacity (consumables, labor, materials) Higher operating costs are somewhat balanced by lower capital and maintenance/utilities costs 20 From Clone to Clinic

21 Thank You! Rick Stock BioProcess Technology Consultants, Inc. 12 Gill Street, Suite 5450 Woburn, MA 01801

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