Session III: Scale-Up Issues: Examples and Effective Solutions

Session Co-Chairs

• Robert Lin, Eastman Chemical Co.
• Shaibal Roy, DuPont

Schedule

Use of Piloting to Reduce Scale-Up Risk

David Berg, DuPont

The scale-up and commercialization of new process technology inherently involves a broad range of business, market, and technology risks that must all be managed in order to be successful.  Companies with a successful track record in scale-up typically have well established processes for risk identification, risk assessment and prioritization, and development and execution of risk mitigation plans.  Piloting is a commonly used strategy for reducing the risk of failure at larger scale due to operational issues (fouling, plugging, corrosion, etc.), recycle problems (build-up of impurities), and process capability issues (low yield and capacity, poor product quality, etc.).

This paper will share learnings from several previous DuPont projects and discuss best practices that have been adopted over the years to effectively manage scale-up risk.  Topics that will be discussed include: risk management and contingency planning, deciding what elements of the process to pilot and why, deciding what scale to pilot at, and technology transfer from pilot to commercial operations.

Design and Scale Up of Fully Continuous Processes including Reaction, Workup, and Isolation

Martin Johnson, Eli Lilly and Company

Several fully continuous processes have been run in Chemical Product Research and Development at Eli Lilly to enable scale up of chemistries that are not suitable for conventional batch equipment. Superheated thermal cyclization, high pressure hydroformylation (70 bar), high pressure asymmetric hydrogenation (70 bar), which were not feasible to scale up in existing in-house batch equipment, have been conducted safely in continuous reactors. Multi-stage counter-current extractive workup enabled higher product yield and better impurity rejection compared to batch.  Continuous crystallization enabled higher ee upgrade compared to batch, seeding only once at the beginning of the campaign, and the quality assurance of steady state operation.

Continuous distillation enabled difficult solvent exchanges with less solvent waste and less residence time in the evaporator compared to batch, and efficient separation of compounds with small relative volatility.  Typical research scale throughputs are 1 to 10 g/h and pilot scale throughputs are 5 to 15 kg/day. Most continuous processes that were run at research and pilot scale in the development laboratories have solids in flow.  Custom methods and devices for slurry mass transport are described.  No mechanical pumps are used for slurry flow. Instead, automated sequenced block valves and pressure swing fluid transfer chambers are used for pumping and flow metering of slurries. 

The Search for the Piloting and Scale-Up Vision of the Future

Brad Duckworth, Eastman

As companies around the globe strive for growth, manufacturing industries have a renewed focus on growth strategies and the chemical industry is no exception. A major factor in the success or failure of a company’s growth strategy is how effectively they implement new technologies. As concepts for new technologies are conceived, it becomes increasingly more important to scale-up these concepts from the idea phase to a profitable manufacturing facility in the most efficient and cost effective means possible.

Eastman Chemical Company decided to take a critical look at their piloting and scale-up methodology and benchmark others in the industry and use this information to develop a new piloting and scale-up vision that would enable Eastman’s growth strategies to become reality. This presentation will cover the approach used to develop Eastman’s new piloting and scale-up vision as well as the concepts behind the vision.

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