Resolution Activities (And Challenges)

A number of global initiatives have been commissioned to take on elements of the transformation challenge. For example, in technology development, programmes are already underway that are required in continuous manufacturing. These include a UK Centre for Continuous Manufacturing and Crystallisation (CMAC), a US-based Novartis-MIT Center for Continuous Manufacturing, the US Centre for Structured Organic Particulate Systems (cSOPS), Ireland SSPC (Synthesis and Solid State Pharmaceutical Centre), various European consortia, and several prototype equipment developments (e.g., UK CMAC Research Partnership Investment Fund). More recently, a new initiative to developing an E2E Supply Chain "eco-system" that considers technology developments (including continuous processing developments) within new supply chain models and the appropriate regulatory regimes required at an industry sector level have been commissioned (UK ReMediES project). These industry-research (and regulator engaged)-based consortia initiatives are enabling sector-wide "pre-competitive" collaborations to support and accelerate transformations to continuous processing.

A key challenge for these teams is in identifying specific product groups where continuous process manufacturing is attractive. Initial research suggests that we should not assume immediately that a SC based on continuous is more flexible and responsive, and that moving an existing product into a continuous (drug product) system may require significant development work. On the development side, we should require much less API for DoEs, engineering runs and validation runs, which will support experimentation where material cost or scarcity is an issue. Another key feature of Continuous Manufacture is that it converts the transformation processes from a strictly stepwise and multiple unit operations-based approach into a world of constant flow of energies and materials. This eliminates the necessity to have holding points before and after each unit operation and eliminates the requirement for the materials to have the ability to survive the holding point without compromising quality. An example is where unit operations are broken up into different geographical locations, to take advantage of duty and tax regimes requiring the shipping of intermediates; these business models constrain the freedom of the process designer and make certain routes impossible, which might otherwise be feasible in continuous manufacturing. On the other hand, in a continuous sequence of processes that are always dynamic, there are limits to possibilities for rework. Also, there is no easy route to stopping a process mid-stream, make a decision, as it is always in flow. Mastered adequately a continuous process offers unique benefits but is not the solution for all cases.