• Represent the entire process on the computer
• Perform material and energy balances
• Explore unit operation alternatives
• Estimate equipment sizes
• Calculate demand for utilities as a function of time
• Estimate the cycle time of the process
• Perform cost analyses
• Assess environmental impact

Simulation is an important process engineering tool for activities like: generating design alternatives, evaluating process performance under various conditions, suggesting process modifications, determination of optimal conditions, bottlenecks or sensitivity to process changes and estimating effluent characteristics.

In terms of modes of operation, chemical processes can generally be classified as batch or continuous. In batch processes, the feedstocks for each processing step are charged into the equipment at the start of the process and the products are removed at the end. The conditions in each processing step are dynamic, changing over time. The transfer of material between equipment units is intermittent. On the other hand, continuous processes allow for continuous flow of materials between processing units and are designed to operate at a steady-state.

Process simulators for continuous chemical processes have been used by the petrochemical industries since the early 1960's. Well-known simulators for the petrochemical industries include: Aspen Plus (Aspen Technology Inc.), ChemCAD (Chemstations, Inc.), HYSYS (Hyprotech, Ltd.) and PRO/II (Simulation Sciences, Inc.).

Simulation of batch processes is more challenging due to their intrinsic, time-dependent behavior. Batch Process Technologies was the first batch process simulator, commercialized under the name Batches in the mid 1980's. Intelligen, Inc., developed SuperPro Designer in the late 1980's. Aspen Technology Inc. introduced Batch Plus in the mid 1990's. Hyprotech Ltd. released Batch Design Kit (BDK) in the late 90's. While the operation models in Batches are dynamic and the simulation involves integration of differential equations over time, Batch Plus, BDK and SuperPro Designer operate with models based on simple algebraic equations to reduce computational time. Batch Plus is recipe driven, which means that the user develops a text recipe and the modeling engine creates a Process Flow Diagram (PFD). BDK and SuperPro Designer provide a graphical user interface that allows the user to directly generate the PFD. SuperPro Designer, originally developed at MIT to address the needs of biopharmaceutical industries, has been expanded over the years to address other industries (synthetic pharmaceuticals, agrochemicals, food processing, microelectronics, etc.) as well as water purification and end-of-pipe treatment processes. While Batches, Batch Plus and BDK are practically limited to batch processes, SuperPro Designer can handle batch and continuous processes equally well.

Because of their history, software packages developed for the petrochemical industry are quite advanced at simulating chemical synthesis processes but considerably underdeveloped for the description of biotechnology operations. There are several challenges in the application of simulation software to the bioprocessing industry. First, pharmaceutical and biotechnology industries typically integrate batch and semi-continuous operations, which can be difficult to simulate. Second, unit operations such as fermenters, homogenizers, centrifuges and chromatography columns, are unique to the bioprocessing industry and are not always well-characterized. Additionally, these unit operations are based on physical and biological phenomena rather than phase equilibrium. Third, raw materials and products are usually under defined (e.g., cells and proteins with unknown physical properties) or complex substrates of varying compositions are used (e.g., yeast extract, soybean meal). Finally, cleaning and sterilization of equipment and final products are necessary for FDA-approved processes and products; thus, the simulation software must include the materials, equipment and scheduling required for clean-in-place (CIP) and steam-in-place (SIP) operations.

A team from the University of Maryland along with Merck and Company evaluated the process simulation software packages Aspen Batch Plus and SuperPro Designer for use in modeling industrial biotechnology processes. They concluded that both packages are best suited to provide a format for process management, using material and energy balances to answer scheduling questions, explore equipment change-outs and perform economic analyses. Although successful performing specific simulation tasks, the ability of the software to accurately predict unit operation scale-up and bioprocess optimization was somewhat limited. The rating for SuperPro Designer was "good", or better, for user friendliness and absence of software bugs, set up time and run time, tracking material balances across the entire process, economic evaluation and modeling unit operations such as fermentation, centrifugation and reaction.

The bioprocessing team at AMI has recently acquired a commercial license to utilize the simulation software SuperPro Designer, by Intelligen, Inc. Our team is pleased to offer chemical process simulation services with over 140 unit operations/procedures, rigorous reactor models including fermenters (Figure 1) and tools to perform process integration and flowsheet development, scheduling of batch operations, thorough process economics, throughput analysis and debottlenecking, waste stream characterization (Figure 2) and environmental impact assessment.

Available literature containing examples of successful SuperPro Designer applications can be found at www.intelligen.com. Some of these include:  

1. Modeling the Process and Costs of Fuel Ethanol Production by the Corn Dry-Grind Process (U.S. Department of Agriculture)
2. Bio-Diesel Production from De-gummed Vegetable Oil (U.S. Department of Agriculture)
3. Production of Polyhydroxyalkanoates from Renewable Carbon Resources (Tokyo Institute of Technology)

We are currently using SuperPro Designer to determine the most feasible and economical alternative to achieve BOD reduction in a glucose-rich industrial waste stream. Special emphasis is being given to aerobic biological treatment, anaerobic digestion and flash vacuum evaporation technologies. The size of the equipment, operational costs, stream characterization and environmental impact are some of the design aspects being determined. The software has allowed us to explore these options under different scenarios, including fluctuations in flow rate and/or BOD loading and seasonal temperature changes among others.

The simulation software allows AMI to serve our clients in a more efficient way, facilitating exploration of options to determine the most feasible one without having to perform experiments for all of the alternatives.

Our bioprocessing interns have expressed their satisfaction using SuperPro Designer, as it is relatively easy to understand and has become a very useful tool for mapping out different design situations and learning about a great variety of unit operations available for use.

References:

(1) Papavasileiou V., Koulouris, A, et al. (2007). Optimize manufacturing of pharmaceutical products with process simulation and production scheduling tools. Chemical Engineering Research and Design, 85 (7), 1086-1097.

(2) Hamouda, M.A., Anderson, W.B., et al. (2009). Decision support systems in water and wastewater treatment process selection and design: a review. Water Science and Technology, 60 (7), 1757-1770.

(3) Petrides, D., Koulouris A., et al. (2002). The role of process simulation in pharmaceutical process development and product commercialization. Pharmaceutical Engineering, 22 (1), 1-8.

(4) Potera C. 1998. Computer simulation systems. Genetic Engineering and Biotechnology News, 18 (16), 10, 29.

(5) Shanklin, T., Roper, K., et al. (2001). Selection of bioprocess simulation software for industrial applications. Biotechnology and Bioengineering, 72 (4), 483-489.