Feed-Forward Process Control Strategy for Pharmaceutical Tablet Manufacture Using Latent Variable Modeling and Optimization Technologies

Abstract

In pharmaceutical tablet manufacturing processes, a major source of disturbance affecting drug product quality is the (lot to lot) variability of the incoming raw materials. A Feed-Forward process control strategy that compensates for raw material variability is presented. The approach involves building PLS (partial least squares) models that combine raw material attributes and tablet process parameters and relate these to final tablet attributes. The resulting models are used in an optimization framework to then find optimal process parameters which can satisfy all the desired requirements for the final tablet attributes, subject to the incoming raw material lots, prior to performing a batch. The connectivity obtained between the three sources of variability (materials, parameters, attributes) can be considered a design space consistent with Quality by Design (QbD) principles, which is defined by the ICH-Q8 guidance [1]. To implement the FF control, an in-house process simulator is presented. The effectiveness of the methodologies is illustrated through a common industrial tablet manufacturing case study.