Simulation Of Bioprocess
ERT 315
3
Modeling
and Assessment in
Process Development
Integrated development of bioprocesses
Process concept
Process design and
development
Improvement
needed
Modeling and
simulation
Sustainability
assessment
Ecoefficient
Industrial application
Not ecoStop
efficient
Literature
Patents
Expert
knowledge
• Close collaboration with the process
design
• Additional information from patents,
literature, and other external sources
• Simulation used to evaluate the process
and guide the R&D to the overall aim
• Repeated iteratively
4
Batch/Bioprocess Modeling,
Scheduling & Optimization
Subject covered
 Modeling and optimization of batch and
continuous processes
 Batch Process Scheduling
 Resources and inventory tracking
Cost analysis & project economic evaluation
 Throughput Analysis & Debottlenecking
What is “Process Simulation”?
Q: What does the word “simulate” mean?
Building a process model
 Predicting how a process would actually
behave
 Performing an experiment (on computer)

Incentives:
 Highly cost effective
 Reasonably accurate
 Proactive approach
The Role of Process Simulation and Scheduling Tools in
Product Development and Commercialization
IDEA GENERATION
Project Screening, Strategic Planning
Development Groups
PROCESS DEVELOPMENT
Evaluation of Alternatives
Common Language of Communication
FACILITY DESIGN
Equipment & Utility Sizing and Design
Development Groups
Process Engineering
Corporate Environmental
Tech Transfer
MANUFACTURING
On-Going Optimization, Debottlenecking
Production Scheduling, Capacity Analysis
Manufacturing
What is a “model” ?
Process Simulation and Enterprise Modeling
“A model should be as simple as possible
and no simpler” – Albert Einstein
INTELLIGEN, INC.
Sequential modular approach
Individual equipment blocks may require
iterative solution algorithms
Overall process solution is sequential & not iterative
(Turton et al., 1998)
Sequential modular approach
Objectives of simulation
• Raw Materials
• Labor
• Utilities
• Capital Expenses
Batch
Process

Size
Throughput
/
Batch
Cycle Time
Waste
Product(s)
Commercial process simulators
SS Simulation
Aspen Plus
Dynamic Simulation
Batch
Oil, Gas &
Petrochemicals
HYSYS
Solids
Pinch
Oleo Chemicals
Specialty Chemicals
Provision
Design II
Phys Prop
Sizing & Costing
Economics
SuperPro
Rating
Sensitivity Analysis
Optimization
SuperPro Designer (SPD)
SuperPro Designer
BioPro Designer
BatchPro Designer
EnviroPro Designer
SchedulePro
Biotechnology
Bio-Fuels
Fine Chemicals
Pharmaceuticals
Food Processing
Mineral Processing
Water Purification
Wastewater Treatment
Air Pollution Control
Scheduling and Debottlenecking
of Multi-Product Facilities
Available tools
•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 & Cycle Time Analysis
• Throughput Analysis & Debottlenecking
• Environmental Impact
• Detailed Reports and Charts for the Above
User Interface of SuperPro Designer
Detailed Modeling using Unit Procedures and Operations
Double-Click
Operations Gantt Chart
Equipment Occupancy Chart
Scheduling Questions
• How can I schedule production during the next 6-18 months?
• How can I schedule operations in an R&D facility?
• How to adjust scheduling if priorities change?
• Can I fit a new product into my facility?
Resource Demand Chart
Labor Demand Chart
Cost Breakdown
Consumables
$0.65/g
29.1%
Raw materials
$0.88/g
39.6%
Raw Materials
Equipment
Labor
Consumables
Lab/QC/QA
Waste Trtm/Disp
Utilities
Facility
$0.54/g
24.4%
Cost Analysis Questions
• What is the required capital investment for a new plant?
• How much would it cost to make a kilo of product?
• Which process is better for making this product? A or B?
• How can I reduce the operating cost of a process?
Environmental
Report
Stream
Dialog – Env. Impact
Properties
Tab
INTELLIGEN, INC.
Bottleneck identification
Debottlenecking Questions
• How much product can I make in this plant?
• What limits the current production level?
• What is the capital investment for increasing production?
Steps in the development of a
bioprocess
Literature/patent review
Biocatalyst screening
Development steps
Biocatalyst optimization
Medium and reaction condition optimization
Selection of downstream steps
Identification of PFD
Optimization of unit operations
Plant size
Scale-up : Lab – technical - industrial
Approval, clinical trials
Process modeling and uncertainty analysis
Economic and environmental assessment
Development process
Product idea
Production
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Goal of every process development: product
Product- should have a market, potential market, sufficient size that economically
justifies the required environment
Required literature and patent review – to clarify if there are similar products already
on the market or in the development
Find a biocatalyst (organism or an enzyme that catalyses the formation of the desired
product)- to reach an economically feasible product yield and concentration
The medium and reaction conditions are adjusted enable the best performance of the
catalyst- medium should be as simple and inexpensive as possible and the reaction
conditions should provide the best environment for the biocatalyst
The process flow diagram (PFD) put together all the operation
All unit operations have to be chosen and connected in an efficient and robust
manner- to maximize the overall yield
Determined the size plant- validate the market share of the product estimated at the
beginning
Scale up the process
Plan and implement the clinical trials for pharmaceuticals
Build a process models to estimate the material balance, energy consumption, labor
requirement and equipment needed
Bioprocess environment
Product
Market/marketing
Health and
environmental
impact
Legal/regulatory
aspects
Safety
Biocatalyst
Molecular biology
Microbiology
Biochemistry
Cultivation
Strategic decisions/
business strategy
Process
Biochemical
and process
engineering
modeling
Supply
chain
Cost
analysis
Patents,
Intellectual
property