(432a) Taking PAT From the Laboratory to Commercial Manufacturing

LaPack, M. A., Eli Lilly and Company
Jeffery, S. B., Eli Lilly and Company
Doherty, S. J., Eli Lilly and Company
Martinelli, J. R., Eli Lilly and Company

Measurements using PAT are applied to two main areas: 1) Gaining process understanding and 2) maintaining process control. The decision to use PAT for control applications is an outcome of the design and development of the process. The parameters to be controlled, the process design space, and control limits dictate the type of technology selected (pH, conductivity, mid-IR, mass spectrometry, etc.) and the user requirements (materials of construction, limit of detection, dynamic range, robustness, etc.).

An example will be presented where a dissolved gaseous byproduct further reacts to form an impurity that affects both product quality and yield. Based on process models, rationales were developed for monitoring either the reaction liquid or the headspace gas during the process designed to remove this gas. The focus of this presentation will be to describe the development of the PAT-based process control system, including discussions about technology selection, vendor selection, risk and contingencies, qualification, installation, and validation.