Eyes on Continuous Equipment
What innovations are enabling a changeover to continuous?
Richard Steiner |
This article was published in our sister publication, The Small Molecule Manufacturer, which celebrates the field of small molecule drug development and manufacturing with interviews and articles focusing on success stories, equipment, and new processing techniques.
I’ll begin by saying that the term “continuous” is, in many cases, incorrectly used — particularly when referring to “truly continuous” or “discrete continuous” solutions. Continuous processing goes beyond putting well-defined unit operations together in a line; it is about transforming indeterminate quantities of raw materials into a final dosage form by controlling the process with an understanding that any deviation of a critical process parameter (CPP) is directly linked to the product’s critical quality attributes (CQAs). A smart process maintains those CQAs within their tolerance limits without risking material loss or end-product quality. Some prominent unit operations already operate in a continuous manner, such as twin-screw extruders or linear powder blenders. Anyone who claims to be able to accurately define the indefinite quantity of a continuous material stream for their own benefits will come to realize that greater engineering minds will relish the reductio ad absurdum argument opportunity… and win!
Continuous manufacturing in pharma is gaining momentum because of the growing realization that it is a very efficient way of making drugs, moving away from stepwise and time-consuming batch methods to a fully integrated and closely controlled process that gives excellent product consistency by intrinsic design. Regulatory agencies, such as the US FDA, are also advocating the implementation of continuous manufacturing. The FDA states: “If drug makers paid more attention to high quality manufacturing, it would prevent the regulatory problems that lead to plant closures and costly fixes. Continuous processing also allows manufacturers to respond much quicker to changes in demand, potentially contributing to the prevention of drug shortages.” (1)
As one example, consider Pfizer’s portable, continuous, miniature and modular (PCMM) pod-based mini factories. The PCMM system accelerates the speed at which tablets are produced and by miniaturizing the equipment, the continuous process can be enclosed in a portable, modular facility, which can be shipped by truck to any location in the world and quickly assembled. Once up and running, the system will deliver the capability to transform powders into uncoated tablets in minutes, which can take days or weeks with current technology.
The argument that continuous manufacturing is best suited for “large-volume, low-cost” medicines is somewhat dated. In fact, we’re seeing the exact opposite. If you look at market approvals and new launches, it’s quite clear that drug manufacturers are testing and challenging the business case for continuous manufacturing with legacy products, and then using the same platforms to develop higher value pipeline products and file for new drug applications.
As long as you have pharmaceutical excipients (or an API) in a formulation that can be dosed with a loss-in-weight feeder, you can use a continuous manufacturing system. Often, the decision whether to use continuous manufacturing or not is based more on the “processability” of the powders rather than throughput considerations. The implementation drivers, however, will differ depending on the product. For small-volume products, time-to-market and production yield are key because of the value of the APIs. For bigger volume drugs, supply chain agility and cost savings are the main drivers for continuous.
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