Equipment

Production equipment is usually not identical to laboratory equipment, just a little bigger. The potential introduction of significant changes has to be addressed.

Scaling-up a downstream process also means converting to hardware components that have a different design than components typically used in flexible small-scale bench-top chromatography systems. This may involve rotary, diaphragm or peristaltic pumps replacing high-precision piston or displacement pumps. Simpler 1-way diaphragm valves replace low volume multi-port valves. Tubing size and length is optimized to reduce system pressure in large-scale chromatography skids.

The difference in hardware design introduced upon scale up can have an impact on the chromatographic performance and may require some fine tuning of the process after scale up to the final production equipment. For example, extra dispersion can be introduced due to increased ratio of total system to column volume that may affect the efficacy of equilibration, washing and elution procedures. Introducing filters, air traps and new design of flow cells and column distribution systems can also contribute to this effect.

Another aspect of scale up is the increase in column diameter which may cause some extra bed compression due to the loss of wall support. This may call for some fine tuning of flow velocity at large scale.

Scale up issues to consider in relation to large scale equipment include:

• Column wall support
• Column distribution system
• Column handling/packability
• Achievable vs. required plate numbers in large scale column
• Extra column zone spreading
• Accuracy in flow velocity and gradient mixing
• Chemical resistance
• Pressure rating
• Hygienic design
• Toxicity of wetted materials

• Adjustment of flow velocity
• Adjustment of equilibration, wash and elution volumes
• Adjustment of gradient volume (or length of steps in step elution)
• Modification of fractionation
• Modification of CIP/SIP routines