Steps Forward in Continuous Manufacturing

Historically, the pharmaceutical industry had the luxury of accepting lower manufacturing utilization rates compared to other manufacturing industries given the higher margins for their products. But as the industry faces increased generic-drug incursion, reduced R&D productivity, and resulting greater profit pressure, containment of manufacturing and supply-chain costs has become evermore important. This need is moving the wheels of  innovation for a new model for pharmaceutical manufacturing, one that offers greater flexibility in aligning product demand with supply. Is continuous manufacturing the solution?

Some think so. The vision for a new manufacturing model came into sharper focus last month with recent advances made by the Novartis–MIT Center for Continuous Manufacturing. The center was formed through a 10-year, $65-million collaboration between Novartis and the Massachusetts Institute of Technology (MIT) in 2007, with the goal of developing a fully integrated platform for continuous manufacturing that would integrate drug-substance manufacturing with finished drug-product manufacturing.

The center is headed by Bernhardt Trout, director at the Novartis–MIT Center for Continuous Manufacturing and professor of chemical engineering at MIT. In a recent news from MIT, Trout and other MIT researchers reported on a prototype continuous-manufacturing system, one that transforms raw materials into tablets in a nonstop process. The research team described the new prototype at last October’s annual meeting of the American Institute of Chemical Engineers, according to the MIT release.

The prototype involves different components, such as reactions between drug precursors, purification, crystallization, tablet formation, and monitoring of the overall process. To demonstrate the system, the researchers built a prototype (24 ft by 8 ft by 8 ft) and also are also working on a smaller, tabletop version of the technology, according to the MIT release. Novartis recently renewed its grant to MIT for a second five-year term, during which the MIT research teams will work on new ways to form tablets, recycle catalysts, and design more complex multistep syntheses, among other projects. Novartis is setting up a pilot plant at its headquarters in Basel, Switzerland, to create a larger-scale version of the flow technology developed at MIT, although commercial rollout would be a longer-term goal, according to the MIT release.

Integrated continuous-flow manufacturing would certainly be a game-changer in the pharmaceutical industry. It has the potential to reduce the size of manufacturing plants, a company’s overall manufacturing footprint, and costs, as well as offer greater flexibility in managing production and product supply. For now, such an approach is only a vision of what may come, but it would represent a manufacturing innovation of immense importance to the industry if such a vision can be brought to fruition.