Define Critical Process Parameters (CPPs) early, preferably at the initial formulation stages of product development. Identify the Critical Quality Attributes of the product first (e.g. dissolution rate for tablets) and think about how those attributes are affected by formulation components, the method of manufacture, process conditions and capabilities of equipment to be used in the process. This provides a foundation for evaluating CPPs and their effects on product quality and process practicality so that the manufacturing process can be developed and optimized in accordance with the principles of Quality By Design (QBD).

In some circumstances, formulation development and early manufacturing process definition can be a hurried affair, often when there is a need to register a proposed product quickly. In such cases, identifying and evaluating CPPs is cursory at best, with the assumption that they will be understood in greater depth during subsequent manufacturing process development or scale-up activities. A disadvantage of this approach is that time and material are expended unnecessarily to identify and evaluate CPPs at a pilot or commercial scale.

Studying CPPs during formulation development before scale-up yields early insight into process design, suitability and robustness while conserving materials and time. Using Statistical Design of Experiments and interpreting results of studies using predictive technologies may take a little extra time and consideration during the formulation development rush, but that time is well spent if the CPPs are thoroughly understood.

The practical result? Robust manufacturing processes which are well-defined and capable of producing products with consistent quality attributes that invariably comply with specifications. Moreover, this approach enables effective technology transfer between organizations and sites.

I would be glad to hear from anyone who shares these views or has interesting experience in defining and controlling CPPs.

Meanwhile, if you would like further information about specific examples that could be applied to your products or processes, please contact me at austin@pharminstinct.com