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Development of a Semi-Continuous Manufacturing Process

Enabled by Process Analytical Technology (PAT)

Continuous processing provides an alternative path to approach process development. Particularly for hazardous syntheses, operating in flow offers significant advantages over the conventional batch mindset of the pharmaceutical industry. Ethyl diazoacetate, a commonly used cyclopropanating reagent, is a great example due to the exothermicity of its synthesis as well as the reactivity and explosivity concerns associated with its storage and transportation.

In this webinar, Ronald Carrasquillo of Bristol Myers Squibb discusses the development of a flow process to safely synthesize ethyl diazoacetate, as well as consume it in a downstream fed-batch reaction, to minimize its handling. The start-to-end process encompasses:

  • A diazotization in flow
  • Aqueous extractions and phase separations
  • Inline degassing
  • Fed-batch cyclopropanation

The use and selection of PAT tools was crucial to the progress of process development and the learnings derived from their application with regards to monitoring and process control and will be a focus of discussion.

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About the Presenter

Ronald Carrasquillo

Ronald Carrasquillo

Principal Scientist, Bristol Myers Squibb

Ronald is a Principal Scientist at Bristol Myers Squibb’s Reaction Science and Engineering group. He received his Ph.D. in Chemical Engineering from the University of Wisconsin – Madison and his Bachelor’s in the same field from the University of Puerto Rico – Mayagüez. He is currently a co-lead for his department’s flow processing group and is involved in various areas, including reaction kinetics, modeling and in-situ monitoring, heterogeneous catalyst synthesis, data mining and visualization, flow processing and teaching. He is an avid reader and currently lives in New Jersey with his wife, dog and three cats.