Abstract

Step-by-step Towards End-to-end: Examples of Integrated Processes for the Continuous Production of Pharmaceuticals

Heidrun Gruber-Wölfler, Associate Professor, Graz University of Technology

The coupling of chemical reactions in flow with a continuous purification is a step further in the development of completely continuous end-to-end manufacturing and has become more and more popular in the pharmaceutical industry in recent years. Probably the most well-known example in this context is the work by the MIT-Novartis Center for the end-to-end manufacturing of the API aliskiren hemifumarate. In our work we focused on the integration of the synthesis with the crystallization of fine chemicals and active pharmaceutical ingredients in flow. The examples that will be presented include reactions using photo- and heterogeneous catalysis set-ups directly linked to continuous crystallization processes. Continuous crystallization was the method of choice as it is a common unit operation for the purification of organic compounds due to its high efficiency, and the low capital and operational costs. Furthermore, in addition to the product purification our methods allow the direct engineering of particle size and shape, which is important for the further formulation steps. The design and integration of these secondary manufacturing processes, including the coupling of the single steps, the real-time analysis methods and the appropriate interfaces, will also be discussed in this presentation.