Post on 15-Dec-2015
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 ConferenceLa Jolla, CA
November 15, 2000
Outline
• Introduction
• Motivation
• Debottlenecking Theory
• Debottlenecking Example
• Cost Analysis
• Conclusions
INTELLIGEN, INC.
Computer-Aided Process Design and Simulation
INTELLIGEN, INC.
• 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.
• 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.
IDEA GENERATIONProject Screening, Strategic Planning
PROCESS DEVELOPMENTEvaluation of Alternatives
Common Language of Communication
FACILITY DESIGNEquipment & Utility Sizing and Design
MANUFACTURINGOn-Going Optimization, Debottlenecking
Process Scheduling, Production Planning
Development Groups
Development GroupsProcess EngineeringCorporate EnvironmentalManufacturing
Manufacturing
The Role of CAPD and Simulation inProduct Development and Commercialization
INTELLIGEN, INC.
INTELLIGEN, INC.
Water PurificationWastewater TreatmentAir Pollution Control
BioPro Designer
SuperPro Designer
BatchPro Designer
EnviroPro Designer
BiotechnologyFood Processing
Synthetic PharmaceuticalsSpecialty ChemicalsAgriChemicals
Who is Intelligen, Inc.?
Established in the early 90’s - MIT spin off
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
Intuitive User Interface
INTELLIGEN, INC.
Double-Click
Detailed Modeling using Unit Procedures and Operations
Flexible Operation Models (Column Elution)
INTELLIGEN, INC.
Operations Gantt Chart
INTELLIGEN, INC.
Throughput Analysis and Debottlenecking Theory
INTELLIGEN, INC.
Debottlenecking of Batch Operations
INTELLIGEN, INC.
Equipment Resources
Types of Bottlenecks
AnnualThroughput
BatchThroughput
xNumber of
Batches per Year=
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
Equipment Capacity Utilization
INTELLIGEN, INC.
EquipmentCapacity
Utilization
Liquid Volume
Max Liquid Volume=
EquipmentCapacity
Utilization
Operating Throughput
Max Throughput=
Equipment Time Utilization
INTELLIGEN, INC.
EquipmentUptime
Total Time Equipment is Utilized per Batch
Effective Plant Batch Time (EPBT)=
EPBT
Equipment Throughput Bottlenecks
INTELLIGEN, INC.
CombinedUtilization
=EquipmentCapacity
Utilizationx
EquipmentUptime
Potential for Throughput Increase
INTELLIGEN, INC.
EquipmentCapacity
Utilization
CurrentBatch
Throughput Conservative Max
EquipmentUptime
EPBT
Current
Realistic
Theoretical
Realistic Max
Theoretical Max
Equipment Throughput Bottlenecks
INTELLIGEN, INC.
Resource Bottlenecks
INTELLIGEN, INC.
Debottlenecking Strategy
INTELLIGEN, INC.
AnnualThroughput
BatchThroughput / 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).
Throughput Analysis Example
INTELLIGEN, INC.
Production of TherapeuticMonoclonal Antibodies
INTELLIGEN, INC.
Base Case Data
INTELLIGEN, INC.
Broth Volume 4,000 L=
Product Titer 1 g/L=
Bioreactor Volume 6,500 L=
Recovery Yield 56%=
Fermentation Time 10 days=
Max Working Volume 6,175 L=
INTELLIGEN, INC.
Equipment Utilization Chart (Base Case)
V-101=Scheduling (Time) Bottleneck
EPBT = 11 daysBatch Throughput = 2.3 kg Batches per Year = 29Annual Throughput = 67 kg
INTELLIGEN, INC.
Capacity, Time, and Combined Utilization Chart (Base Case)
65%=Capacity Utilization of Bottleneck Equipment
Scenario 1
INTELLIGEN, INC.
New Results
ActionIncrease batch size by 54% (broth volume 4,000 L 6,175 L)
Batch throughputNumber of Batches per YearAnnual Throughput
3.55 kg29 103 kg
WarningsChromatography columns cannot handle new batch in 2 cycles.Action Increase # of cycles per batch from 2 to 3.
INTELLIGEN, INC.
Capacity, Time, and Combined Utilization Chart (Scenario 1)
100%=Capacity Utilization of Bottleneck Equipment
EPBT = 11 daysBatch Throughput = 3.55 kg Batches per Year = 29Annual Throughput = 103 kg
Scenario 2
INTELLIGEN, INC.
ObservationDownstream section is underutilized in time.
ActionIntroduce new bioreactor and stagger its operation based on the new time bottleneck equipment.
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 kgNumber of Bioreactors = 2
Scenario 3
INTELLIGEN, INC.
New Results
ActionAdd extra diafilter to eliminate current time bottleneck.
Batch throughputNumber of Batches per YearAnnual Throughput
3.55 kg44 (29 39 44) 156 kg
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 kgNumber of Bioreactors = 2
V-103=Scheduling (Time) Bottleneck
Scenario 4
INTELLIGEN, INC.
New Results
ActionAdd extra storage tank to eliminate current time bottleneck.
Batch throughputNumber of Batches per YearAnnual Throughput
3.55 kg58 (29 39 44 58) 206 kg
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 kgNumber of Bioreactors = 2
V-101=Scheduling (Time) Bottleneck
Scenario 5
INTELLIGEN, INC.
New Results
ActionAdd extra bioreactor and diafilter.
Batch throughputNumber of Batches per YearAnnual Throughput
3.55 kg84 (29 39 44 58 84) 298 kg
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 kgNumber of Bioreactors = 3
V-105=Scheduling (Time) Bottleneck
Comparison
INTELLIGEN, INC.
Scenario Number
BioreactorVessels
Batchesper Year
AnnualThroughput
1 1 29 103 kg
2 2 39 138 kg
3 2 44 156 kg
MembraneDiafilters
3
3
4
BatchThroughput
3.5 kg
3.5 kg
3.5 kg
3.5 kg4 2 4 58 206 kg
0 1 29 67 kg3 2.3 kg
3.5 kg5 3 5 84 298 kg
StorageTanks
3
3
3
4
3
4
Labor Demand as a Function of Time
INTELLIGEN, INC.
WFI Demand as a Function of Time
INTELLIGEN, INC.
Cost Analysis
INTELLIGEN, INC.
Cost Analysis Results (Base Case)
Equipment Cost
Total Investment
Operating Cost
Unit Cost
$2.3 M
$25.4 M
$12.9 M/yr
$193/g
Production Rate 67 kg/yr
Distribution per Section
Upstream
Downstream
43 %
57 %
DFC-Dependent
34%
Consumables29%
Raw Materials27%
Waste Disposal4%
Labor-Depended5%
Lab/QC/QA1%
INTELLIGEN, INC.
Comparison of Various Options
Ba
se
Ca
se
Sc
en
ari
o 1
Sc
en
ari
o 2
Sc
en
ari
o 3
Sc
en
ari
o 4
Sc
en
ari
o 5
0
50
100
150
200
250
300
Unit Cost ($/g)
Annual Throughput (kg)
INTELLIGEN, INC.
Cost Analysis Results (Scenario 5)
Operating Cost
Unit Cost
$41.1 M/yr
$138/g
Production Rate 298 kg/yr
Distribution per Section
Upstream
Downstream
38 %
62 %
DFC-Dependent
13%
Consumables39%
Raw Materials36%
Waste Disposal5%
Labor-Depended6%
Lab/QC/QA1%
INTELLIGEN, INC.
Key Assumption
Unit cost of raw materials andconsumables remained unchanged
SuperPro Designer v5.0
INTELLIGEN, INC.
Spring 2001
INTELLIGEN, INC.
SuperPro v4.5 (current)
• Scheduling and Planning• Resource Tracking• Equipment Utilization• Debottlenecking
Single-Recipe Project Multi-Recipe Project
Perform at the Facility Level
From Single to Multiple-Recipe Projects
SuperPro v5.0
SuperPro Project Databases
Recipe 1
Recipe 2
Recipe 3
Multi-ProductManufacturing
Facility
Facilities
Equipment
ConstructionMaterials
Labor
Utilities
RawMaterials
INTELLIGEN, INC.
Project Architecture
Sites
Display of Multi-Recipe Projects
INTELLIGEN, INC.Worksheets (recipes)
Summary
• Facilitating Process Development
• Improving Team Communication
• Increasing Plant Throughput
• Reducing Capital and Operating Cost
INTELLIGEN, INC.
Process Simulation can play a role in:
For a fully functional demo of SuperPro Designer
&A book chapter on
Bioprocess Design & EconomicsGo to
www.intelligen.com