Experiences in batch trajectory alignment for pharmaceutical process improvement through multivariate latent variable modelling

The primary objective of batch data as trajectory alignment (or synchronization) is to standardize the data sampling per batch according to the evolution of the process, and secondarily to homogenize the samples per run. The use of an indicator variable performs both objectives well. Two examples from the pharmaceutical sector are discussed to illustrate the different ways to deal with uneven samples across batches and across variables in the same batch. Since trajectory alignment requires large time investment, a simple triage approach is proposed to assess the need to analyze the dynamics of a given process and hence perform alignment. The presented examples are representative of a broad variety of batch processes that are operated by recipe in the pharmaceutical sector. In our experience, the variables associated with the automation triggers in these recipes are the best indicator variables to use for alignment. This is due to (i) the fact that the trigger variables are easy to identify from the automation of the recipe, (ii) operators are familiar with these, (iii) the target values for triggers are known a priori and hence the resulting alignment scheme can be performed in real-time for monitoring applications and (iv) it makes the monitoring scheme easy to understand and justify around the design-space since the design-space may originally be defined in terms of the trigger variables for each phase of the batch.

► The objective of Batch trajectory alignment is discussed.
► Different options to synchronize batch data from an automated recipe-driven process are explored.
► The “indicator variable” is the best approach to synchronize data of this nature.
► Dynamic Time Warping is unnecessary to align batch data from an automated recipe-driven process.