Table 1.

Common Scale-up mistakes vs. recommended approaches.

Mistake	Recommended approach
The first-of-a-kind process was never piloted	Pilot the process and use pilot data to design and build the large-scale plant
Performance unexpectedly deviated at scale and target metrics were not achieved	Use large-scale models to identify critical scale-up parameters and evaluate them in lab/pilot scale-down tests as early and often as possible
The engineering and construction teams had never designed or built a similar plant before	Use an engineering design, procurement and construction team that has worked on a similar project before
Industrial grade raw materials were never validated ahead of scale-up	Validate all industrial raw materials in lab/pilot studies ahead of procurement
The operations team wasn’t trained prior to plant start-up	Give your operations team training and operating experience in the pilot plant
Plant utilities were unreliable	Engineer in utility redundancy where feasible and validate utilities ahead of start-up; understand how utility interruptions will impact your process
There were no systems in place to properly transfer technology or troubleshoot process deviations	Install lab-scale fermentors in the plant lab to facilitate technology transfer and process troubleshooting
Sterility validation of fermentation systems was skipped	Perform a rigorous sterility validation program that assesses the entire sterile boundary
Critical equipment or instrumentation was eliminated to cut cost	Identify and install equipment/instruments that are critical for process monitoring and control
The operations team did not know how to respond to process upsets, resulting in lost batches/product	Perform rigorous process upset testing at lab/pilot scale and develop a detailed upset response plan; train the operations team both in the pilot plant and by using process simulators
There was no preventive maintenance program in place; equipment losses resulted in significant production delays	Put in a place a preventive maintenance program and hire skilled maintenance engineers; identify critical process equipment (e.g. valves, pumps) and keep back-ups on-site
Poor project management resulted in significant delays	Assign a skilled, dedicated project manager to coordinate and oversee activities
Business and technical management imposed unrealistic constraints on project cost and schedule	Resist pressures to overpromise; stress test plans with domain experts; identify and weigh project execution risks against rewards and penalties
There wasn’t enough money available to run the plant once it was built	Reserve enough time to properly commission and start-up the plant with enough money to weather any storms