In a pursuit of improving safety and process efficiency, Biogen a top Biotech company collaborated with Proteaf Technologies and Flowid to scale up a highly hazardous lithium-halogen exchange followed by quench reaction sequence at ChemConnection, Oss, NL. The sequence demonstrated successful scale up of laboratory spinning disk technology to the SpinPro– a production scale spinning disc reactor developed and manufactured by Flowid.
In batch, lithium-halogen exchange requires very low temperatures, i.e. < – 50oC in order to minimize impurity formation, and the reaction typically uses larger volumes of solvent in order to control the heat generated by the process. Although both microreactor and spinning disc reactors can dramatically improve the energy dissipation, spinning disc reactor has a clear advantage in the ability to handle solids.
It has been proven that with the use of spinning disc reactor (both lab scale Synthetron and production scale SpinPro), not only was the volumetric efficiency improved more than two-fold as compared with both batch and microreactors, but the reactor produced material of equivalent high quality despite using half the solvent, and a substantially smaller footprint than other types of continuous reactors.
Lab to Manufacture in a Single Step:
Based on preliminary chemical feasibility studies by the American process intensification company Proteaf Technologies, a set of experimental runs for the SpinPro reactor were designed and completed. Analytical results showed excellent correlation with the small scale feasibility experiments—allowing for direct scale up from 15 mL lab scale reactions using the Kinetichem SynthetronTM—a lab scale spinning disk reactor– to production rates of 100 of Kg’s per hour raw material in the SpinPro reactor, or 20Kg per hour of product with conversions greater than 95%. Currently work is underway to understand full capacity and customer demand for this process within the fine, pharma, and specialty chemical markets.
Pilot Plant Scalability that Fits Through the Door:
For performing the halogen-lithium exchange reaction on the SpinPro Reactor, the reactor and additional equipment was transported and installed at the facilities of ChemConnection, Oss, NL. ChemConnection is a research and manufacturing organization, capable of handling the safety requirements for the large-scale synthesis using pyrophoric reagents under cGMP conditions required by the pharmaceutical industry.
The reactor footprint of 1 m2 allows the unit to be installed virtually anywhere where service lines can be connected, such as between existing fixed equipment. Start-to-finish sensor communications for process monitoring and data logging are built into the reactor and can be customized depending on chemistry.
Flowid is breaking new ground by reducing the size of process equipment. We do this based on our own technology, but also by cooperating with partners, and integrating their technology in our solutions. The philosophy remains the same: to create small environments for precise control to boost process performance in terms of efficiency, safety and flexibility. Flowid can be reached at NL +31.624.679.774
About Proteaf Technologies
Proteaf offers scalable application specific solutions based on off-the-shelf instrumentation supported by custom engineering and chemistry research and development services. Proteaf offers Lab-to-Manufacture continuous process intensification solutions for virtually any process where there may be a business benefit. Capable to implement continuous processing into your development program at your lab through a network of global talent, Proteaf offers feasibility studies, process research, and develops cutting edge applications using a number of continuous technologies. Proteaf can be reached at US 1.845.536.4244.
This article has been written by Robert Tinder Ph.D. and Wouter Stam, MSc
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