(384c) Operational Control Strategy Development Via First Principles Mapping

Product and Operational control strategies are essential elements in efficient and effective manufacturing of quality medicines. Many forms of guidance exist (e.g., PQLI) to help define and structure documented control strategies. Most control strategies are good at identifying the controlled variables and critical parameters that are essential to ensure product quality. What is often missed, however, is identifying the underlying first principle transformations that are the core of every deliberate step that is taken in making medicine. Each process step has an objective to be met. In fact, when we look at each process step, there are multiple objectives to be met. We must ensure the product quality is delivered, but we must also ensure that we do it cost effectively, protect the operator, protect the community, protect the environment, meet demand, etc. To manufacture the Product, we must design a Process Map as a collection and sequence of Process Stages and Process Operations that combine to deliver certain features and requirements of the product. The process operation is simply stated as an action (or transformation) on an object with a qualifier, e.g. Disperse powder to less than 1% variation. The mechanisms for transformation can always be traced to first principles of science. Thus, the Control Strategy is based upon key first principles and associated attributes and variables, at the most fundamental level. To satisfy the criteria of the transformation we must choose and implement effective Control Methods. For the example of "disperse powder", we might choose a vertical agitated tank that will deliver an adequate environment for the first principles attributes of shear and fluid velocity. For each process operation, we must consider objectives and control methods for all Features, such as quality, safety, cost, etc. In the case of Safety, for example, we can provide control methods for preventing dust explosions based upon the first principles of ignition source control.

This presentation will define and demonstrate the means to construct and implement a structured product control strategy via process mapping using first principles-based transformations and chosen control methods.