Coming from the Semiconductor Industry and other related industries, it always seems obvious to me that at some stage the concept of Continuous Drug Manufacture could become a reality at some stage. It would appear that we are much closer than you would imagine. Also it is a fact that the Pharma industry in Ireland must rapidly start to develop the thought processes and skills to position itself for the future.
At AAPS 2010 in New Orleans, James Evans, Associate Director of the Novartis-MIT Center for Continuous Manufacturing, presented a blue-sky vision of what integrated continuous manufacturing in pharma can look like, and suggested that the future is not as far off as we might think.
To date, major efficiency gains have already been implemented within the drug manufacturing arena, Evans said, and “additional quantum gains” in batch processing are limited. So we need a paradigm shift, he said, one that:
- Makes manufacturing more economically viable and sustainable
- Is “cleaner, leaner, and more energy efficient”
- Offers the potential to leverage new chemistries. “Continuous manufacturing is not new, and we can leverage continuous work in other industries and areas,” he said.
The Novartis-MIT Blue Sky Vision includes “fully integrated continuous manufacturing, where the end goal is everything flows continuously through with no separation—drug substance and drug product become one!”
Achieving this vision, Evans noted, will require the implementation of Quality by Design principles, new product development processes, new facility layouts, and, “major changes” in the technical skills of the engineers and other professionals who run these processes.
Evans then discussed, very generally, the work his team is doing to achieve this end-to-end continuous vision. He showed a flow chart illustrating a reconfigured manufacturing process the Center expects to have up and running next year, and to have a more advanced version operating by 2015. “We’ve eliminated approximately 40% of unit operations,” he noted.
In one instance using this process, the Center produced one kilo of API in 37 hours, whereas the counterpart batch process took 259 hours. “Regardless of drug product, manufacturing time of continuous is trivial compared to batch,” Evans said.
Economic studies the Center has done show that converting an existing process from batch to continuous can save approximately 7% to 14% of costs, and with optimization using the blue-sky approach, between 15% and 50%.
Additional blue-sky benefits:
- A reduction in development time
- A manufacturing footprint reduction of 40% to 90%
- Significantly reduced inventory
- Lower QC costs due, for example, to reduced waste and improved material flow
Evans claimed that Novartis-MIT’s continuous paradigm has the potential to decrease product throughput from 200-300 days (a traditional range) or 100-150 days (a Lean manufacturing range) to “in the order of less than ten days getting the product to the patient!”
Lastly, Evans outlined the next steps that need to be taken to realize some of these benefits across the industry:
- “We have to embed continuous process development into manufacturing sites,” he said. The earlier it gets embedded in product development, the more buy-in it will get in commercial manufacturing.
- Technology innovation: “We need universities who have the time and capabilities to develop new technologies, the pharma companies to be engaged, the process automation and software companies to be engaged, and the analytical and process equipment companies to be involved.”
- Operator Transformation: Most operators today are lower-skilled, unit-operation focused. “For continuous manufacturing, we need to transform the operator. The system is highly automated and requires a high-skilled operator who understands the entire process.”
- Lastly, the value proposition needs to be developed and communicated.
It is a very exciting future but have we the skills, facilities, strategies, regulations and support to make this future a reality in Ireland.
Finbarr Sheehy