(621a) Integration of Orthogonal PAT Tools to Facilitate API Process Development

Integration of Orthogonal PAT Tools to Facilitate API Process Development
Jeffrey Nye, Dimitri Skliar, Gregory Beutner

The Reaction Science and Engineering group at BMS is a multidisciplinary team of chemists and chemical engineers that utilizes first principles-based understanding of reactions and engineering fundamentals to optimize chemical processes, generate knowledge and enable robust manufacturing strategies for active pharmaceutical ingredients (API). A focus area for the group is in supporting data-rich experimentation, wherein during experimental execution, data streams from many disparate sources are captured, aggregated and contextualized in real time. By expanding the scope of easily-accessible data streams, lab scientists are able to maximize the knowledge generated from individual experiments, achieving the goals of increased understanding with shortened development timelines.

Here we present a series of case studies wherein process development is enabled by the incorporation of two or more orthogonal process analytical technologies (PAT). These real-time tools provided critical insights into complex chemical systems enabling knowledge generation on lab scale, and process control on large scale. In one case study we describe the simultaneous use of FTIR, NIR and hydrogen uptake to map the kinetics and understand diastereoselectivity of a reductive amination using anhydrous ammonia. In the second case study we couple Raman spectroscopy and real-time microscopy with off-line techniques to elucidate the chemical behavior of inorganic carbonate bases in a metathesis reaction involving a poorly-soluble intermediate with complex form behavior. The data-rich platforms provided by PAT in both case studies allowed for the rapid understanding and decision-making that are critical to enable a dynamic and complex API portfolio.