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Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes INTELLIGEN, INC. Simulation and Design Tools for the.

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Presentation on theme: "Throughput Analysis, Debottlenecking, and Economic Evaluation of Integrated Biochemical Processes INTELLIGEN, INC. Simulation and Design Tools for the."— Presentation transcript:

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

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

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

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

5 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? Cost Analysis Questions INTELLIGEN, INC.

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

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

8 Tool Description - Overview INTELLIGEN, INC. 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. Double-Click Detailed Modeling using Unit Procedures and Operations

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

12 Operations Gantt Chart INTELLIGEN, INC.

13 Throughput Analysis and Debottlenecking Theory INTELLIGEN, INC.

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

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

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

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

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

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

20 Equipment Throughput Bottlenecks INTELLIGEN, INC.

21 Resource Bottlenecks INTELLIGEN, INC.

22 Debottlenecking Strategy INTELLIGEN, INC. Annual Throughput Batch Throughput / Effective Batch Time   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 Throughput Analysis Example INTELLIGEN, INC. Production of Therapeutic Monoclonal Antibodies

24 INTELLIGEN, INC.

25 Base Case Data INTELLIGEN, INC. Broth Volume4,000 L = Product Titer1 g/L = Bioreactor Volume6,500 L = Recovery Yield56% = Fermentation Time10 days = Max Working Volume6,175 L =

26 INTELLIGEN, INC. Equipment Utilization Chart (Base Case) V-101 = Scheduling (Time) Bottleneck 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) 65% = Capacity Utilization of Bottleneck Equipment

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

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

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

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

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

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

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

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

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

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

38 Comparison INTELLIGEN, INC. Scenario Number Bioreactor Vessels Batches per Year Annual Throughput kg kg kg Membrane Diafilters Batch Throughput 3.5 kg kg kg32.3 kg 3.5 kg kg Storage Tanks

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

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

41 Cost Analysis INTELLIGEN, INC.

42 Cost Analysis Results (Base Case) Equipment Cost Total Investment Operating Cost Unit Cost $2.3 M $25.4 M $12.9 M/yr $193/g Production Rate67 kg/yr Distribution per Section Upstream Downstream 43 % 57 % DFC-Dependent 34% Consumables 29% Raw Materials 27% Waste Disposal 4% Labor-Depended 5% Lab/QC/QA 1% INTELLIGEN, INC.

43 Comparison of Various Options Base Case Scenario 1 Scenario 2 Scenario 3 Scenario 4 Scenario Unit Cost ($/g) Annual Throughput (kg) INTELLIGEN, INC.

44 Cost Analysis Results (Scenario 5) Operating Cost Unit Cost $41.1 M/yr $138/g Production Rate298 kg/yr Distribution per Section Upstream Downstream 38 % 62 % DFC-Dependent 13% Consumables 39% Raw Materials 36% Waste Disposal 5% Labor-Depended 6% Lab/QC/QA 1% INTELLIGEN, INC. Key Assumption Unit cost of raw materials and consumables remained unchanged

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

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

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

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

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

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


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