The CONTINUUS<br />Advantage


Integrated Continuous Manufacturing (ICM), initially developed at the Novartis-MIT Center for Continuous Manufacturing, enables seamless end-to-end continuous manufacturing processes that incorporate API formation steps with final drug product formulation. In doing so, we can provide significant advantages compared to outdated batch production.

Advancing Pharmaceutical Manufacturing

Although the pharmaceutical companies excel in the discovery of new therapeutics, they are behind many other industries in their manufacturing methods. Batch manufacturing is an outdated methodology that suffers from a series of “stop-and-start” steps in its production chain.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 (see figure below). Consequently, lead times are very long, sometimes over a year from raw materials to finished products, and the required plant footprint is very large. It is estimated that the pharmaceutical industry loses over $50 billion a year in inefficient processes.


With ICM, everything is automated and seamless. Intermediates flow from unit to unit, without the typical stops-and-starts that characterize batch processes. Real-time monitoring and control allow for robust processes with improved quality assurance. Key advantages afforded by this novel strategy include:

Quality: Manufacturing quality is significantly improved with ICM. Smaller process volumes allow for more control, and a plantwide QbD strategy with continuous monitoring and real-time feedback and feed forward control ensures that the final product will be maintained within the required specifications (i.e., state of control).
Costs: ICM can reduce the cost of manufacturing significantly. Important contributors include reduced/smaller equipment, improved yields, fewer steps, decreased personnel, and less testing. Cost reductions can range from 30% to over 50%.
Lead time: By removing unnecessary steps and the inefficient stops and starts typically required for batch testing, ICM can reduce lead times from many months to just a few days.
Plant footprint: With ICM, unnecessary steps are removed, equipment is smaller, work-in-process inventory is eliminated, and fewer personnel are required.
Environmental impact: Higher yields, lower solvent requirements, and efficient solvent recovery systems are important ICM features.
Process development: ICM will provide access to design space not achievable with large-volume batch equipment. For example, important parameters, such as the surface area-to-volume ratio, are greatly increased as process volume decreases, enabling certain reactions (e.g., exothermic nitrations).
Safety: As stops and starts are eliminated through the seamless nature of ICM, any unstable or toxic intermediates will be immediately consumed by the next step (i.e., no buildup).
Clinical Trial Manufacturing: As clinical trials progress (i.e., phase I→phase II→phase III), ICM lines would just need to be run for longer time periods to accommodate the larger volumes, eliminating the need for scale-up activities that often bottleneck drug development.

High Potency and Special Cases

The integrated nature of ICM processes eliminates points of human exposure – process material and intermediates remain in situ, and are transported across the different unit operations through automated and closed processes. This is particularly beneficial for manufacturers of high potency compounds, where containment challenges are significant. Furthermore, the small in-process volumes characteristic of ICM systems further improve operator safety.

Processes with unstable or explosive intermediates can also benefit significantly from ICM implementation. This is because with ICM processes, these intermediates are generated on demand, and are immediately consumed (i.e., they are not isolated and then manually transported to the next step), reducing the build-up of such dangerous materials.

Additional Advantages

Due to its unique features, such as its use of novel continuous technologies, ICM can provide advantages across the entire supply chain (see figure below).

Additionally, with its low-lead time/on-demand nature, ICM could facilitate the simplification of today’s complicated current drug distribution network. This will reduce costs significantly and improve patient access to life-saving drugs.

Case Study

The CONTINUUS team was able to demonstrate significant operational advantages In the production of a high-volume generic compound.

Process development

From targeted solutions, such as the application of a single continuous unit operation, to end-to-end processes, CONTINUUS will work with clients to address specific needs. The modular and flexible nature of ICM allows for a broad range of product offerings.

targeted solution

The unit operations that comprise our Integrated Continuous Manufacturing lines are novel, and provide advantages over existing conventional batch technologies. They permit reactions and formulation steps that are not possible in batch.