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Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes

Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes. Demetri Petrides, Ph.D. President. IBC Conference La Jolla, CA November 15, 2000. INTELLIGEN, INC. Simulation and Design Tools for the Process and Environmental Industries. INTELLIGEN, INC.

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Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes

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  1. Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes Demetri Petrides, Ph.D. President IBC Conference La Jolla, CA November 15, 2000 INTELLIGEN, INC. Simulation and Design Tools for the Process and Environmental Industries

  2. INTELLIGEN, INC. Outline • Introduction • Motivation • Debottlenecking Theory • Debottlenecking Example • Cost Analysis • Conclusions

  3. INTELLIGEN, INC. Computer-Aided Process Design and Simulation

  4. INTELLIGEN, INC. Debottlenecking Questions • How much product can I make in this plant? • What limits the current production level? • What is the min capital investment for increasing production?

  5. INTELLIGEN, INC. Cost Analysis Questions • How much would it cost to make a kilo of product? • What is the required capital investment for a new plant? • Which process is better for making this product? A or B? • How can I reduce the operating cost of a process?

  6. INTELLIGEN, INC. The Role of CAPD and Simulation in Product Development and Commercialization IDEA GENERATION Project Screening, Strategic Planning Development Groups PROCESS DEVELOPMENT Evaluation of Alternatives Common Language of Communication Development Groups Process Engineering Corporate Environmental Manufacturing FACILITY DESIGN Equipment & Utility Sizing and Design MANUFACTURING On-Going Optimization, Debottlenecking Process Scheduling, Production Planning Manufacturing

  7. BioPro Designer BatchPro Designer EnviroPro Designer SuperPro Designer INTELLIGEN, INC. Who is Intelligen, Inc.? Established in the early 90’s - MIT spin off Biotechnology Food Processing Synthetic Pharmaceuticals Specialty Chemicals AgriChemicals Water Purification Wastewater Treatment Air Pollution Control

  8. INTELLIGEN, INC. Tool Description - Overview • Intuitive User Interface • Wide Variety of Unit Operation Models • Databases for Components and Mixtures • M&E Balances of Integrated Processes • Equipment Sizing and Costing • Project Economic Evaluation • Process Scheduling • Throughput Analysis & Debottlenecking • Waste Stream Characterization

  9. Intuitive User Interface

  10. INTELLIGEN, INC. Detailed Modeling using Unit Procedures and Operations Double-Click

  11. INTELLIGEN, INC. Flexible Operation Models (Column Elution)

  12. INTELLIGEN, INC. Operations Gantt Chart

  13. INTELLIGEN, INC. Throughput Analysis and Debottlenecking Theory

  14. Types of Bottlenecks Resources Equipment Annual Throughput Batch Throughput Number of Batches per Year = x INTELLIGEN, INC. Debottlenecking of Batch Operations

  15. = Scheduling (Time) Bottleneck Tank (V-101) INTELLIGEN, INC. Equipment Scheduling (Time) Bottlenecks Auxiliary Equipment (e.g., CIP and SIP skids) and resources also can become time bottlenecks.

  16. Liquid Volume Operating Throughput Max Liquid Volume Max Throughput INTELLIGEN, INC. Equipment Capacity Utilization Equipment Capacity Utilization = Equipment Capacity Utilization =

  17. EPBT Total Time Equipment is Utilized per Batch Effective Plant Batch Time (EPBT) Equipment Uptime = INTELLIGEN, INC. Equipment Time Utilization

  18. Equipment Capacity Utilization Combined Utilization Equipment Uptime = x INTELLIGEN, INC. Equipment Throughput Bottlenecks

  19. Batch Throughput Current Conservative Max Realistic Max Theoretical Max INTELLIGEN, INC. Potential for Throughput Increase Equipment Capacity Utilization EPBT Current Equipment Uptime Realistic Theoretical

  20. INTELLIGEN, INC. Equipment Throughput Bottlenecks

  21. INTELLIGEN, INC. Resource Bottlenecks

  22. / Annual Throughput Batch Throughput Effective Batch Time  INTELLIGEN, INC. Debottlenecking Strategy •  Increase batch throughput until a size bottleneck is reached. • Then, • Increase number of cycles of limiting procedure; • Rearrange equipment, or; • Use new equipment (stagger operation).

  23. INTELLIGEN, INC. Throughput Analysis Example Production of Therapeutic Monoclonal Antibodies

  24. INTELLIGEN, INC.

  25. INTELLIGEN, INC. Base Case Data = Broth Volume 4,000 L = Bioreactor Volume 6,500 L = Max Working Volume 6,175 L = Product Titer 1 g/L = Recovery Yield 56% = Fermentation Time 10 days

  26. = Scheduling (Time) Bottleneck V-101 INTELLIGEN, INC. Equipment Utilization Chart (Base Case) EPBT = 11 days Batch Throughput = 2.3 kg Batches per Year = 29 Annual Throughput = 67 kg

  27. INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Base Case) Capacity Utilization of Bottleneck Equipment = 65%

  28. INTELLIGEN, INC. Scenario 1 Action Increase batch size by 54% (broth volume 4,000 L  6,175 L) Warnings Chromatography columns cannot handle new batch in 2 cycles. Action  Increase # of cycles per batch from 2 to 3. New Results Batch throughput Number of Batches per Year Annual Throughput 3.55 kg 29 103 kg

  29. INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Scenario 1) Capacity Utilization of Bottleneck Equipment = 100% EPBT = 11 days Batch Throughput = 3.55 kg Batches per Year = 29 Annual Throughput = 103 kg

  30. INTELLIGEN, INC. Scenario 2 Observation Downstream section is underutilized in time. Action Introduce new bioreactor and stagger its operation based on the new time bottleneck equipment.

  31. = Scheduling (Time) Bottleneck DF-102 INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Scenario 2) EPBT = 196 h (initial 264 h) Batches per Year = 39 (initial 29) Annual Throughput = 138 kg Number of Bioreactors = 2

  32. INTELLIGEN, INC. Scenario 3 Action Add extra diafilter to eliminate current time bottleneck. New Results Batch throughput Number of Batches per Year Annual Throughput 3.55 kg 44 (29  39  44) 156 kg

  33. = Scheduling (Time) Bottleneck V-103 INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Scenario 3) EPBT = 171.5 h (264 h  196 h  171.5) Batches per Year = 44 (29  39  44) Annual Throughput = 156 kg Number of Bioreactors = 2

  34. INTELLIGEN, INC. Scenario 4 Action Add extra storage tank to eliminate current time bottleneck. New Results Batch throughput Number of Batches per Year Annual Throughput 3.55 kg 58 (29  39  44  58) 206 kg

  35. = Scheduling (Time) Bottleneck V-101 INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Scenario 4) EPBT = 130.3 h (264 h  196 h  171.5  130.3) Batches per Year = 58 (29  39  44  58) Annual Throughput = 206 kg Number of Bioreactors = 2

  36. INTELLIGEN, INC. Scenario 5 Action Add extra bioreactor and diafilter. New Results Batch throughput Number of Batches per Year Annual Throughput 3.55 kg 84 (29  39  44  58  84) 298 kg

  37. = Scheduling (Time) Bottleneck V-105 INTELLIGEN, INC. Capacity, Time, and Combined Utilization Chart (Scenario 5) EPBT = 89.7 h (264 h  196 h  171.5  130.3  89.7) Batches per Year = 84 (29  39  44  58  84) Annual Throughput = 298 kg Number of Bioreactors = 3

  38. INTELLIGEN, INC. Comparison Scenario Number Bioreactor Vessels Membrane Diafilters Storage Tanks Batches per Year Batch Throughput Annual Throughput 0 1 3 3 29 2.3 kg 67kg 1 1 3 3 29 3.5 kg 103kg 2 2 3 3 39 3.5 kg 138kg 3 2 4 3 44 3.5 kg 156kg 4 2 4 4 58 3.5 kg 206kg 5 3 5 4 84 3.5 kg 298kg

  39. INTELLIGEN, INC. Labor Demand as a Function of Time

  40. INTELLIGEN, INC. WFI Demand as a Function of Time

  41. INTELLIGEN, INC. Cost Analysis

  42. Consumables 29% Waste Disposal 4% Distribution per Section Upstream 43 % Downstream 57 % INTELLIGEN, INC. Cost Analysis Results (Base Case) Lab/QC/QA Production Rate 67 kg/yr 1% Equipment Cost $2.3 M Raw Materials 27% Total Investment $25.4 M Operating Cost $12.9 M/yr Labor-Depended DFC-Dependent 5% 34% Unit Cost $193/g

  43. 300 250 200 150 100 Unit Cost ($/g) 50 0 Annual Throughput (kg) Base Case Scenario 1 Scenario 2 Scenario 3 Scenario 4 Scenario 5 INTELLIGEN, INC. Comparison of Various Options

  44. Consumables 39% Waste Disposal 5% Distribution per Section Upstream 38 % Downstream 62 % INTELLIGEN, INC. Cost Analysis Results (Scenario 5) Lab/QC/QA 1% Production Rate 298 kg/yr Raw Materials 36% Operating Cost $41.1 M/yr Unit Cost $138/g DFC-Dependent Labor-Depended 13% 6% Key Assumption Unit cost of raw materials and consumables remained unchanged

  45. INTELLIGEN, INC. SuperPro Designer v5.0 Spring 2001

  46. INTELLIGEN, INC. From Single to Multiple-Recipe Projects SuperPro v4.5 (current) SuperPro v5.0 Single-Recipe Project Multi-Recipe Project Perform at the Facility Level • Scheduling and Planning • Resource Tracking • Equipment Utilization • Debottlenecking

  47. Equipment Raw Materials Construction Materials Labor Utilities INTELLIGEN, INC. Project Architecture Databases SuperPro Project Recipe 1 Sites Recipe 2 Recipe 3 Facilities Multi-Product Manufacturing Facility

  48. INTELLIGEN, INC. Display of Multi-Recipe Projects Worksheets (recipes)

  49. INTELLIGEN, INC. Summary Process Simulation can play a role in: • Facilitating Process Development • Improving Team Communication • Increasing Plant Throughput • Reducing Capital and Operating Cost

  50. For a fully functional demo of SuperPro Designer & A book chapter on Bioprocess Design & Economics Go to www.intelligen.com

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