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The Role of Process Simulation during the Life Cycle of Process Development and Product Commercialization The use of process simulators and other modeling tools is gaining quick acceptance in the biotech, pharmaceutical, and specialty chemical industries. Such tools are mainly used to evaluate "what-if" scenarios and to optimize integrated processes. Specific tasks handled by process simulators include: material and energy balances of integrated processes, equipment sizing, cost analysis, scheduling of batch operations, environmental impact assessment, throughput analysis and debottlenecking. Process simulation tools can be used throughout the life cycle of process development and product commercialization. The figure below illustrates the benefits of simulation tools at various stages of the commercialization process. These benefits are explained in greater detail below.

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Idea Generation. When product and process ideas are first conceived, process simulation is used for project screening/selection and strategic planning based on preliminary economic analyses.

Process Development. While the pre-clinical and clinical testing of the candidate drug compound is going on, the company's process development group is looking into the many options available for manufacturing, purifying, characterizing the drug substance, and formulating it as a drug product. At this stage, the process undergoes constant changes. New synthetic routes are being investigated, and new recovery and purification options are being evaluated. Alternative formulations are also explored. Typically, a large number of scientists and engineers are involved in the improvement and optimization of individual processing steps. Simulation tools at this point can introduce a common language of communication and facilitate team interaction. A computer model of the entire process can provide a common reference and evaluation framework to facilitate process development. The impact of process changes can be readily evaluated and documented in a systematic way. Once a reliable model is available, it can be used to pinpoint the most cost-sensitive areas the economic hot-spots of a complex process. These are usually steps of high capital and operating cost or low yield and production throughput. The findings from such analyses can be used to focus further lab and pilot plant studies in order to optimize those portions of the process. The ability to experiment on the computer with alternative process setups and operating conditions reduces the costly and time-consuming laboratory and pilot plant effort.

The environmental impact of a process is another issue that can be readily evaluated with computer models. Material balances calculated for the projected large scale manufacturing reveal the environmental hot-spots. These are usually process steps that require solvents or regulated materials with high disposal costs. Environmental issues not addressed during process development may lead to serious headaches during manufacturing. This is because after a process has been approved by the regulatory agencies, it is extremely costly and time-consuming to make process changes. This is particularly true for biopharmaceuticals where it is commonly said that "the process makes the product".

Facility Design and/or Selection. With process development near completion at the pilot plant level, simulation tools are used to systematically design and optimize the process for commercial production. Availability of a good computer model can facilitate the transfer of process technology and facilities design. If a new facility needs to be built, process simulators can be used to size process equipment and supporting utilities, and estimate the required capital investment. In transferring production to existing manufacturing sites, process simulators can be used to evaluate the various sites from a capacity and cost point of view and select the most appropriate one. The same can apply to outsourcing of manufacturing to contract manufacturers.

Manufacturing. In large scale manufacturing, simulation tools are primarily used for process scheduling, debottlenecking, and on-going process optimization. Simulation tools that are capable of tracking equipment utilization for overlapping batches can identify bottleneck candidates and guide the user through the debottlenecking effort.