376a Integration of PAT for the Development and Scale-up of a Hydrogenolysis Reaction

Jale Müslehiddinoglu1, Paul Lobben1, Thomas Laporte1, Lori Spangler1, Daniel Fichana2, Shih-Ying Chang1, Donald Kientzler1, Sushil Srivastava1, John Venit1, Robert Wethman3, and San Kiang1. (1) Process R&D, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, NJ 08903, (2) Csm, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, NJ 08903, (3) Analytical R&D, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, NJ 08903

Although the Cbz deprotection reaction is a common organic reaction in the pharmaceutical industry, challenges were faced during the development and scale-up of this reaction at the API step due to the instability of the product in the reaction mixture. This led us to develop a control strategy as a part of quality by design approach. Consequently, a PAT (Process Analytical Technology) was used for continuous monitoring and control in order to ensure the quality of the product. This talk will describe the development of three in-process controls, using kinetics information from FTIR monitoring.