Tablets & Capsules


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C 18 September 2014 Tablets & Capsules continuous manufacturing Continuous tablet manufacturing: Faster development and greater efficiency David Ross Aesica Pharmaceuticals Tablet manufacturing has changed little in the last 50 years. For the most part, materials continue to be dispensed, blended, gran- ulated, dried, compressed, and coated one batch at a time. This article describes the benefits of continuous tablet manufacturing. granulation step, which can be used in combination with blending and/or milling before or after granulation. The result: From initial blending to the production of uncoated tablets takes as little as 20 minutes. We plan to begin manufacturing a market-ready pharmaceutical product—which was developed on our line—later this year, an industry first. One "variable space" for development and manufacture There are several advantages to continuous manufac- turing, and one key advantage is that the same equipment can be used during development and manufacturing. As a result, companies can develop the process and register small batch-manufactured lots using the same equipment and parameters in the same "variable space." That eases scale-up compared to batch manufacturing because the size of the equipment changes very little. With batch manufacturing, the size of the equipment must increase as the batch size increases, dramatically altering the ratio of surface area to volume. That, in turn, leads to big differences in how the equipment handles the product versus what occurred in the development stage. Consider, for example, V-type or bin blenders, which in a research setting are typically 1 to 2 feet tall. Production versions, however, stand one or two stories high. Not only does that potentially affect processing requirements, it requires investing in more equipment should you need to increase the batch size. Furthermore, continuous manufacturing requires less physical space, so the footprint of the combined processes is smaller than that of batch processes. In just 6 months, we transformed an existing GMP area in our building to accommodate a complete continuous process- ing line. It spans 167 square meters and includes a materi- als airlock, a processing room, a washroom, and a person- nel airlock. There is also a 21-square-meter tablet printing area. The system has already produced registra- tion batches for use in Phase III clinical trials. Indeed, the equipment used in continuous processing is often two or more orders of magnitude smaller than that used in batch processes but produces an equivalent ommercial pressure to shorten development times, improve the efficiency of drug development, and reduce the amount of API required is driving a trend toward con- tinuous processing. At the same time, regulators are encouraging manufacturers to establish processes that incorporate the FDA's Quality by Design (QbD) and Process Analytical Technology (PAT) initiatives. All of these trends dovetail with the push toward faster, more efficient pharmaceutical manufacturing. Continuous tablet manufacturing uses the same unit operations as batch processing but connects the equip- ment using real-time process analysis and product charac- terization technology. While new to the pharmaceutical industry, the approach has been standard in the chemical, food, and other process industries for decades. Today's shift toward continuous solid dosage manufac- turing builds on the success of companies that manufacture large volumes of over-the-counter drug products, vitamins, and dietary supplements. Those companies, especially in large markets like the USA, were the pioneers in continu- ous operation of dry granulation, tabletting, and tablet coating. Now the momentum is building among manufac- turers of prescription drug products and in other markets. It has even drawn the attention of contract development and manufacturing organizations (CDMOs). Indeed earlier this year, my company installed a continuous processing line that starts by blending the excipients and API and ends with compressed cores ready for coating. While several major pharmaceutical manufacturers and universities have invested in research facilities dedicated to end-to-end continuous processing, Aesica is the first CDMO to commercialize the technology. Our effort shows that it is indeed possible to link a range of processes upstream of tablet compression, even the wet

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