This coming October, we will celebrate Pharma Manufacturing’s 20-year anniversary as a publication. Our premier issue — from Fall 2002 — contains an article titled, “Think small: Pharma facilities could boost capacity and slash costs by trading in certain batch operations for continuous versions.”
Suffice it to say, the concept of continuous manufacturing is not new to pharma — and yet, discussions on the topic still pack the room at industry events. Such was the case during the “Continuous manufacturing — What’s driving adoption?” panel discussion at CPhI North America last month, indicating that pharma is still on board the continuous manufacturing journey.
Current state of continuous
In the early days, going ‘all in’ on CM was not advised. “One would not propose changing batch processes to fully continuous ones in pharmaceutical production — the products still need to be produced in lots to maintain the proper quality control,” the author of Pharma Manufacturing’s 2002 article cautioned.
During the CPhI panel discussion, panelists recalled how continuous manufacturing was historically viewed as an R&D tool. According to Kai Donsbach, COO at Medicines for All Institute, CM's adoption was driven by its applicability in specific situations — often used for safety when hazardous chemicals were involved, for example. But CM’s usefulness has broadened.
“There has been a change in mindset,” said Donsbach. Now, according to Donsbach, the pharma industry has reached the second stage, having moved from “curiosity mode” into “efficiency mode.”
The drive towards continuous in the commercial manufacturing setting has picked up momentum, and CM is “coming into its own,” said Bikash Chatterjee, CEO of Pharmatech Associates. Most major innovator pharma companies are currently undertaking some type of CM project.
According to Chatterjee, this shift has largely been enabled by the evolution of the regulatory landscape.
Regulatory blessing
One of the major benefits of continuous manufacturing, according to Donsbach, is how it enables manufacturers to “understand the process at any given time.”
By facilitating the use of on-line monitoring and control, CM can bring about increased product quality assurance in real time. This is one of the reasons why the FDA has consistently expressed support of CM; however, regulatory requirements have not always been clear enough to put manufacturers’ minds at ease. But that too, is changing.
"It's quite an extraordinary thing to sit down with the FDA and brainstorm solutions for your process design and control strategy," said Chatterjee. "We are in a nexus right now — a beautiful position where the agency is very open and excited about learning from industry."
Last summer, the International Council for Harmonisation (ICH) published a draft version of new CM guidelines, ICH Q13, for public commentary. As a founding regulatory member of ICH, the FDA plays a major role in the development of each of the ICH guidelines, which FDA then adopts and issues as guidance to industry.
The new Q13 guidance clarifies the definition of a continuous process and provides insight into what manufacturers need to focus on in order to establish control strategies through process models.
According to Donsbach, the long-awaited Q13 guidance will change the landscape for CM, making it more accessible to pharma manufacturers.
Keeping momentum
The panel agreed that there is still work to be done to further propel continuous manufacturing into the mainstream.
One need, according to Chatterjee, is standardization in equipment design — so that adapting CM equipment to different products is not such an “engineering exercise.” This would also help lower the capital investment costs associated with continuous manufacturing.
The panel concluded that increasing regulatory clarity, better technology and a changing mindset are all playing a role in edging continuous manufacturing closer to its full global potential.
