About scale-up

Origin and scope

The term 'scale-up' has been in use since the 1940s to describe the transition from small scale laboratory to kilo lab, pilot plant and ultimately full scale manufacturing. Maintaining process performance (e.q. quality, yield, productivity) on scale is a challenge in every sector of the process industries, whether petrochemicals, polymers, paints or pharmaceuticals.

Why does performance change on scale?

Process performance may change on scale because while molecular-level thermodynamics, equilibria and chemical kinetics are scale-independent, the rates of physical transport processes are scale-dependent and vary with equipment selection, operating conditions and size. Scale-up is arguably more difficult in pharmaceuticals than in other sectors, given the high volume of development projects; on the other hand, repeated use of multi-purpose equipment provides good opportunities for equipment characterization.

Further reading

Here is a list of links and references to help you find out more about scale-up.

Process Development: Physicochemical Concepts, by John Atherton and Keith Carpenter, an Oxford Chemistry Primer

This is one of the best books you can read about process development, with an emphasis on fine chemicals and pharmaceutical process development. Available from Amazon.

Handbook of Industrial Mixing: Science and Practice, edited by Edward L. Paul, Victor Atiemo-Obeng, Suzanne M. Kresta

This book describes how fluid mixing, an important factor for many chemical processes, changes with scale, equipment design and operating conditions. Available from Amazon.

Journal of Organic Process Research and Development

The American Chemical Society produces this journal and articles on scale-up are regularly featured. You can search the journal for scale-up articles here.

DynoChem Resources

The DynoChem Resources website contains a list of more than fifty publications and presentations by pharmaceutical and fine chemicals companies relating to characterization and scale-up of reactions, distillation, crystallization, filtration and other operations.