By Geir Rune Flåten, Chief Solutions Officer
“Potential API savings of more than 60% and time-to-market reduced by more than a year have been identified by companies using small-scale CM systems. In 10 years, the vast majority of tablets will be produced on CM lines that are installed in modular facilities that are a fraction of the size of current plants.”
This quote from GEA’s corporate website highlights the key drivers behind Continuous Manufacturing (CM), and I’m a firm believer. It will happen. However, one of the key concerns before leaving the current world of big batch manufacturing is the control strategy. How do you control a flowing CM process, which basically contains the same elements as traditional batch tablet manufacturing: Blending, wet granulation, drying, blending, compression and coating?
You want to take full advantage of the agility and responsiveness in the CM approach by early detection using online monitoring. When the material leaves one processing step to enter another you have a logical transition point, where you need to be in control. If material does not meet defined values, it is discarded. But it’s more likely your early detection via process-integrated measurement tools have already given you a warning, so the process was adjusted and put back on target. The control model should take advantage of logical sequences and transition points within the CM process. This provides for a logical control regime supporting a modular approach to CM.
Continuous Manufacturing is QbD-friendly
Continuous Manufacturing is for good reasons highlighted as the way forward. It will probably be one of the most significant changes in the pharmaceutical industry in the next 10 years. Flexible development options will facilitate the commercial manufacturing process based on greater process understanding with smaller quantities of material. The FDA endorses CM as it is Quality-by-design friendly of nature.
For several decades batch-based production of blockbusters dominated the pharma industry, but now in the post-blockbuster era material costs during drug development have come to attention. New drug products will be manufactured in smaller quantities. Costs, risks and timelines in traditional batch-based development and manufacturing is being questioned. In most industries, CM is seen as the low-cost solution to producing low value, high volume products.
“Our key suggestion is to base your control strategy on process measurement tools and focus on the transition points within the overall manufacturing process. It is a continuous process, but the control strategy will be based on a step-by-step approach to secure the overall quality of the end product.”
Advantages and challenges
The ability to obtain more data from less product during development and eliminate the cost and risk of batch-based “scale-up” has been a key driver of small-scale, continuous equipment. CM offers to process small quantities of material during R&D while also being able to operate for more time and provide for commercial production.
While being QbD-friendly Continuous Manufacturing offers a series of advantages: Cost efficient for smaller quantities, scalable without scale-up, less inventory, smaller footprint, portability of manufacturing facilities and ability to localize. Among the challenges for getting these benefits are the necessary adaption of equipment, cost of investment, the change-over time in the plant and material tracking and traceability.
Step-by-step quality control
Also control strategy is an issue. Camo is already working with customers, and we support a series of monitoring processes: At-line physical and chemical properties, hardness and weight, online assay and particle size distribution. Our key suggestion is to base your control strategy on process measurement tools and focus on the transition points within the overall manufacturing process. You want to utilize the responsiveness, the agility and the possibility for small changes in the pulse of the manufacturing process. At the transition points you want to be in total control before adding new processes to the material. It is a continuous process, but the control strategy will be based on a step-by-step approach to secure the overall quality of the end product.
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