MSD’s Process Safety Scale-Up Methodology for Pilot Plant Scale and Beyond

Abstract

Process safety testing is critical for small molecule active pharmaceutical ingredient (API) scale-up and manufacturing by proactively identifying any process safety hazards, including environmental and industrial hygiene issues. The intent of this contribution is to describe how Merck & Co., Inc. Kenilworth, NJ (known as MSD outside of the U.S. and Canada) manages process safety testing for pilot plant and manufacturing scale operations with a stagewise approach. Several case studies will be discussed.

Process Safety in the Pharmaceutical Industry─Part II: Process Safety Labs and Instruments Used in Process Safety Labs for Thermal Hazards

“…This includes starting materials, intermediates, reactants, catalysts, and wastes; (b) the reaction at the desired process temperature; and (c) materials and reaction mixtures under the worst-case scenarios (e.g., undesired decomposition if the temperature control of an equipment malfunctions). There are several illustrations available in the literature where calorimetries helped PSLs in the chemical and pharmaceutical industries to successfully identify potential hazards and subsequently develop strategies to mitigate those risks. − For example, potential process safety hazards of 45 common peptide coupling reagents were studied using DSC (differential scanning calorimetry) and ARC (accelerating rate calorimetry), where these instruments helped scientists identify thermally unstable coupling reagents …”