Although the pharmaceutical industry excels in the discovery of new therapeutics, it is behind many other industries in the way it manufactures its products through batch processes. Batch manufacturing is an outdated methodology that suffers from a series of “stop-and-start” steps in its production chain. This includes the isolation and transportation of chemical intermediates (including the active pharmaceutical ingredient, API) across the different unit operations and facilities, where issues with quality can occur (Figure 1). Consequently, lead times are greater than 200 days, from raw materials to finished products, and the required plant footprint is very large. Also, analytical tests are performed on every batch to determine if it meets quality standards (Quality by Testing). All in all, the pharmaceutical industry wastes $50 billion a year in inefficient processes.
Figure 1. Pharmaceutical Manufacturing via Batch Processes
To change this manufacturing paradigm, Novartis invested $65 M in a joint research endeavor at MIT in 2007 to launch the Novartis-MIT Center for Continuous Manufacturing. The Center would span over 10 years, and lead to the creation of novel continuous manufacturing technologies for pharmaceuticals. To date, the project has been extremely successful, and has led to the development of the first prototype process that produces finished drug tablets from raw chemical ingredients through a fully integrated, non-stop, end-to-end continuous process (i.e. Integrated Continuous Manufacturing, ICM, Figure 2). More specifically, the process consists of novel state-of-the-art small-scale process technologies that can be integrated into a seamless manufacturing process. In this way, raw materials can be continuously transformed into finished tablets without interruption (24hrs/day) in just two days, using a single facility with a footprint of 1/10 compared to existing batch plants. Also, quality improves through a plant-wide Quality by Design (QbD) strategy, where automated corrective actions occur in real-time during manufacturing to mitigate process disturbances and allow for real-time release of pharmaceuticals. This ensures that medicines are within pharmaceutical specifications during the entire production cycle.
Figure 2. Schematic of Integrated Continuous Manufacturing (ICM) of Pharmaceuticals
Consequently, Novartis has initiated the technology transfer to its novel continuous manufacturing unit, named the “Technikum,” in Basel, while CONTINUUS Pharmaceuticals was launched to apply the ICM technology to the broader pharmaceutical industry. CONTINUUS has signed an exclusive license with MIT (co-exclusive with Novartis) for a number of novel unit operations developed at the Novartis-MIT Center for Continuous Manufacturing.
Through implementation of ICM, CONTINUUS can produce medicines at significantly reduced costs (30% – 50% reduction), with reduced lead times (90% reduction from industry standard), and of better quality.