Process Analytical Technology Beyond Real-Time Analyzers: The Role of Multivariate Analysis

Abstract

Process analytical chemistry was recognized by Callis et al. (Analytical Chemistry, 59 (1987): 624A–635A) (1) as a field that extends well beyond real time measurements of process parameters. Process Analytical Technology is taking central stage with the 2004 guidance from the Food and Drug Administration, with a mandate much wider than real time measurements. The pharmaceutical industry is entering a new era. Chemometrics has played an integral part for the real time development of process analytical measurements (multivariate calibration) and it is ready to face the challenge of Process Analytical Technology in this wider definition. The scope of this paper is to demonstrate that multivariate, data based statistical methods, can play a critical role in process understanding, multivariate statistical process control, abnormal situation detection, fault diagnosis, process control and process scale-up, as linked to process analytical technology.

Keywords:

• process analytical technology
• multivariate statistical process control
• scale-up
• latent variables
• process understanding
• multivariate analysis