Webinar: Late-Stage Pharmaceutical Development of Nemtabrutinib (MK-1026) at MSD
Utilizing Data-Rich Experimentation to Derive Kinetic and Data-Driven Reaction Models in Late-Stage Pharmaceutical Process Development
Program Overview
- Utilizing data-rich experimentation and laboratory automation to generate reaction kinetics data for a DoE
- Creation of a data-driven reaction model via dynamic response surface modeling
- Leveraging a data-driven model to increase first principles understanding and to facilitate the development of a mechanistic model
Nemtabrutinib is a small molecule reversible inhibitor of Bruton’s tyrosine kinase for the treatment of several hematological malignancies. Synthesis of the active pharmaceutical ingredient (API) leverages nucleophilic aromatic substitution to combine an aryl chloride and an amino alcohol tosylate salt under basic conditions. This presentation will discuss the use of data-rich experimentation (DRE) to generate large datasets via automation and high-throughput studies to characterize the API step reaction.
A key challenge in developing this reaction was determining the robust set of process parameters that would maximize the conversion of starting materials while limiting the formation of by-products. To identify these conditions more efficiently, time-series data from DRE characterization that leveraged a Design of Experiment (DoE) structure were utilized to collect reaction profiles. In addition, data-driven and knowledge-based methodologies were explored, including Dynamic Response Surface Model (DRSM) and mechanistic modeling. The results of this investigation informed process optimization for the synthesis of nemtabrutinib.
About the Presenter
Morgan Crawford
Senior Scientist, MSD Corp.
Morgan is a Senior Scientist at MSD Corp. in Chemical Engineering Research and Development. In her current role, Morgan supports process development, pilot plant demonstrations, and technology transfer for pharmaceutical processes. Prior to her current role, Morgan spent 6 years in the MSD Manufacturing Division where she completed three rotational assignments in the Manufacturing Leadership Development Program and subsequently worked in vaccine process development and commercialization.
