(655b) An Integrated Design Space Involving All Unit Operations in Tablet Manufacturing

A design space can be determined per unit operation, per cluster of unit operations or for the entire process.

By linking unit operations, and therefore recognizing a continuum in drug production that spans from the  Drug Substance Properties to the Drug Product, it is possible to create a more versatile and robust Design Space. The final product that delivers the active pharmaceutical ingredient to a patient, is indeed the result of a multidimensional combination of raw material attributes and process parameters that span several unit operations including those of the drug substance production (like reaction and  crystallization), the ones from drug product production (like granulation and compression) but also  packaging. Each one of them can impact one or more final quality characteristics, as well as stability. 

Therefore, if the Design Space is addressed in a holistic form, then the quality of the final product, including its stability, should be expressed as the result of the values and the interactions of these parameters.   Also by treating the design space in a holistic way it would provide the manufacturer with the most cost efficient operation and provide for high yield and low operating costs, because problems at later unit operations would most likely be anticipated and corrected in earlier operations. In other words the control strategy will be part of the product design, such that it can be implemented in the most cost effective way.  In this model, the tablet manufacturing process is mapped from start to end, and both design space and control strategy can be more dynamic as an observation at the extreme ends of the design space can be offset elsewhere in the process to provide conforming material. 

This works gives an example where all unit operations are integrated in the Design space. Variables from all unit operations are incuded for continued process verification. The work includes different  strengths of tablets