(8a) Microreactor Technology as an Integrated Method for Producing Fine Chemicals

Microreactor Technology enables processes to be run in a continuous manner using a minimal quantity of reagent. Thus, it permits the rapid and scalable development of continuous processes in the fine chemical and pharmaceutical industries. Under such circumstances, advantages are associated in a first instance from the continuous way of operation and in a second instance to the micro structure itself such as the good thermal control. It is important to differentiate from where the advantage is coming from because it will significantly influence the scale up strategy for larger productions.

In the fine chemical industry, productions are made in multi-purpose plants of high flexibility. The integration of a continuous system is such an environment is feasible given appropriate modules are employed with (i) good chemical resistance (i.e. glass, Hastelloy, Teflon), with (ii) excellent material stability over a large range of temperatures, and with (iii) ease of connection avoiding dead volume. In addition the various modules need to take into account the physico-chemical properties of the reaction such as the reaction kinetics (?± residence time) and the reaction phases (solid - liquid - gas). This approach leads systematically to a Toolbox concept.

A detailed analysis at Lonza [1] showed that ca. 50% of the reactions studied could fit into a microreactor based on their kinetic. However, by taking into account the reaction phases, this number shrinks to ca. 20% of potential candidates because a solid phase is present in more than 60% of the cases. In addition, the reactions were classified into 3 classes namely Type A (mixing controlled reactions), Type B (rapid but kinetically controlled reactions), and Type C reactions (batch reactions with thermal hazard).

The goal of Lonza in the past 3 years was to define the needs of this Toolbox. Collaboration with partners such as Corning, Siemens, and IMM were undertaken. We developed 3 reactor modules now called: Module A, B, and C. The presentation will detail the 3 type of modules. These modules are now commercially used at Lonza and several tons of products were synthesized with them. Some manufacturing examples will be presented showing the applicability of Microreactor Technology as an integrated method for producing fine chemicals.

In addition, the lecture will also address in a detailed manner the scale-up strategies available for larger productions. The requirements for a process in clinical phases and later in commercial production are quite different and this difference drives the distinctive needs in the supply chain of fine chemicals. These factors strongly influence the scale-up, multi-scale, or numbering-up strategies.