Symposium on Process Safety and Crystallization

On Tuesday, November 2, METTLER TOLEDO held its 1st Symposium in Cambridge, MA, hosted by Novartis Institutes for BioMedical Research (NIBR). The success of the Symposium went beyond expectations: 65 scientists representing a large variety of small companies (CoNCERT, Cubist, Tetraphase), larger companies (Pfizer, Dow, Amgen), and research institutions (Massachusetts Institute of Technology) attended the event. The main themes of the Symposium were crystallization and process safety. Des O’Grady and I started by giving an overview of the technologies later covered by the industry speakers: Focused Beam Reflectance Measurement (FBRM®), Particle Video Microscope (PVM®), EasyMax™, RC1, and ReactIR™.Chemical Process Development Symposium

Mark Barrett from the Solid State Pharmaceutical Cluster in Ireland presented a calibration-free approach to supersaturation control using a combination of EasyMax™ and ReactIR™ as a strategy used for the development and scale-up of crystallization processes. He also illustrated how FBRM® and PVM® are used to characterize particle size and shape in situ to ensure batch-to-batch repeatability and minimize downstream processing times during filtration drying and formulation. Mark had to leave early to attend the 9th International Conference and Exhibition Polymorphism & Crystallization organized by Scientific Update the following day in Florida, USA.

Jay Larrow from Novartis Institutes for BioMedical Research (NIBR) gave an interesting perspective on how to approach process safety in a discovery environment where scale-up means minimal changes to the initial synthetic route, fast sample delivery of clinical candidates, and a 20L glass jacketed vessel. Jay uses preliminary reaction heat flow assessment in EasyMax™ to estimate ΔTad at the 2-L scale, as well as differential scanning calorimetry for thermal stability. There is little doubt that many small and medium scale pharmaceutical companies in the Boston area could benefit from this pragmatic, time efficient approach to early-on safety assessment.

After Jay’s presentation, I gave an overview of simple and practical applications of reaction progress kinetic analysis in early process research and development using modern software technologies – such as iC Kinetics™. A few case studies demonstrated how simple continuous monitoring technologies (gas uptake, calorimetry) and more sophisticated ones (e.g. ATR-FTIR) combined with graphical reaction progress analysis can help troubleshoot chemical processes, better understand catalyst stability, and optimize chemical transformation more rapidly and more effectively. The chemical reactions used were among those typically used to build complex molecules: e.g. cross-coupling, and hydrogenation reactions.

Finally, Steve Stefanick, Research Fellow and Head of the Process Safety lab at Janssen Pharmaceutical Companies of Johnson & Johnson, gave us a broad perspective on how process safety is handled in a large pharmaceutical company. Steve’s deep interest and years of experience could be seen through the many anecdotes and case studies, as well as the internet resources he provided:

Steve is a long term contributor to the process safety field. His presentations at our past International Process Development Conferences (IPDC) and online seminars can be watched on the AutoChem Community website or can be found on our webinar library.

Two refreshment breaks in the afternoon and a get-together evening networking event in a local restaurant gave participants plenty of time to cultivate the sense of community the scientists in the region are known for. Kudos to Kara Cournoyer from NIBR and Zoe Fernandez (METTLER TOLEDO) for such a great organization, and many thanks to Novartis – and Jay Larrow in particular – for allowing us to use NIBR auditorium.