Innovative approaches to consider include, but are not limited to: (a) PAT real-time monitoring and feed-forward controlling of the powder blending process (see the guidance for industry PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance) and (b) use of statistical process control tools to monitor the powder blending process and to maintain a state of control.
When a manufacturer decides to implement PAT or other process-monitoring and control techniques for powder blend homogeneity assessment, its decision should be supported with appropriate data and rationale using a science- and risk-based approach. For example, the effective sample size of powder examined by PAT probes has to be estimated such that the scale of scrutiny of the PAT powder blending monitoring can be justified (Wu, Tawakkul, et al. 2009). The number of PAT probes and their locations also have to be justified. If a scientifically sound PAT monitoring and control strategy is established, it can facilitate the assessment of (a) variability across locations within the powder bed (El-Hagrasy, Morris, et al. 2001), (b) variability over time of one location, and (c) potential correlation between the powder sample and the unit dosage form.