Issue link: https://www.e-digitaleditions.com/i/377863
amount. For example, the rolls of a roller compactor used in continuous manufacturing are only slightly larger than those of lab-scale units. As a result, formulators can collect data quickly to support regulatory dossiers. That allows products to be fast-tracked so they reach patients more quickly. The smaller equipment also requires less material during development, which reduces or eliminates delays when APIs or other materials are in short supply. Continuous processing also saves money, even at the development stage. A design-of-experiment study con- ducted on our line, for example, requires 80 to 90 percent less API than it would on a standard batch line. With APIs costing $200,000 or more for development quanti- ties, companies could save millions early on by using con- tinuous processing. Naturally, establishing a continuous tablet manufacturing system requires substantial investment. But once in place, the line can operate 24 hours a day, 7 days a week, and reduce production costs. If demand for a product increases, the line simply runs for a longer period. There is little waste during manufacturing and yields typically exceed 97 per- cent. Cleaning the line is time consuming, however, mean- ing production schedules take on great importance. Meeting QbD and PAT Continuous processing also meshes with the FDA's drive to improve quality using QbD, which has been the subject of numerous meetings, seminars, and discussions for the last decade. QbD calls for a full understanding of all the process parameters of a complex variable space, which allows manufacturers to reduce risk, make products and processes more robust, and facilitate a reliable, scien- tific approach to process validation. If the process must be changed, a continuous line requires only small quantities of materials to set up, run, and monitor it, enabling you to quickly access the effects of multiple variable combinations using a minimal amount of API. Conversely, the larger volumes of batch equipment limit the number of combinations and hence the statistical robustness of the validation. The traditional trial-and-error method of optimizing different process steps and formula- tion parameters remains expensive and time consuming. Our continuous manufacturing line uses two at-line monitors, but other systems may include online process analyzers that can evaluate and control quality in real time. The data lead to high-quality products, high- throughput, and lower unit costs, and it's the kind of automation and process monitoring that the FDA was seeking when it began to emphasize PAT. Analytical methodologies use Raman spectroscopy, near infrared, and laser diffraction to assess key process parameters, such as blend uniformity, assay, water con- tent, and particle size. Many if not most are non-invasive, real-time measurements. Likewise, automatic sampling enables technicians to monitor tablet dimensions, break- ing strength, and other attributes. That increases the amount of data available, adding precision and robustness to process validation. Quality assurance Theoretically, when a PAT-based process demonstrates that a process is running within the validated variable space, there is no need to conduct most of the quality- control tests that batches require. Naturally, manufacturers 20 September 2014 Tablets & Capsules The continuous tabletting line at Aesica.