1. Simulation Of Bioprocess ERT 315

2. 3 Modeling and Assessment in Process Development

3. Process design and development Modeling and simulation Sustainability assessment Stop Process concept Industrial application Literature Patents Expert knowledge Eco- efficient Not eco- efficient Improvement needed Integrated development of bioprocesses

4. 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

5. 4 Batch/Bioprocess Modeling, Scheduling & Optimization

6. 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

7. 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

8. 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 Production Scheduling, Capacity Analysis Development Groups Process Engineering Corporate Environmental Tech Transfer Manufacturing The Role of Process Simulation and Scheduling Tools in Product Development and Commercialization

9. What is a “model” ?

10. Sequential modular approach Individual equipment blocks may require iterative solution algorithms Overall process solution is sequential & not iterative (Turton et al., 1998)

11. Sequential modular approach

12. Objectives of simulation Process Throughput Batch Size / Batch Cycle Time  Raw Materials Labor Utilities Capital Expenses Product(s) Waste

13. Commercial process simulators Oil, Gas & Petrochemicals Oleo Chemicals Specialty Chemicals Aspen Plus HYSYS Provision Design II SuperPro SS Simulation Dynamic Simulation Batch Solids Pinch Phys Prop Sizing & Costing Economics Rating Sensitivity Analysis Optimization

14. SuperPro Designer (SPD) Water Purification Wastewater Treatment Air Pollution Control BioPro Designer SuperPro Designer BatchPro DesignerEnviroPro Designer Biotechnology Bio-Fuels Fine Chemicals Pharmaceuticals Food Processing Mineral Processing SchedulePro Scheduling and Debottlenecking of Multi-Product Facilities

15. 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

16. User Interface of SuperPro Designer

17. Double-Click Detailed Modeling using Unit Procedures and Operations

18. Operations Gantt Chart

19. Equipment Occupancy Chart

20. 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? Scheduling Questions

21. Resource Demand Chart

22. Labor Demand Chart

23. Cost Breakdown Raw materials $0.88/g 39.6% Facility $0.54/g 24.4% Consumables $0.65/g 29.1%

24. 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? Cost Analysis Questions

25. Environmental Impact Report

26. Bottleneck identification

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

28. Steps in the development of a bioprocess Development steps Development process Product idea Production Literature/patent review Biocatalyst screening 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

29. 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

30. Biocatalyst Molecular biology Microbiology Biochemistry Cultivation Process Biochemical and process engineering modeling Bioprocess environment Cost analysis Supply chain Strategic decisions/ business strategy Health and environmental impact Patents, Intellectual property Legal/regulatory aspects Safety Product Market/marketing