For more than 20 years, the batch-based production of blockbuster solid dosage forms dominated the industry. Profitability was such that companies were not incentivized to innovate or risk developing new manufacturing technology. However in the post-blockbuster era, it is increasingly recognised that material costs during drug development are significant, new drug products are likely to be manufactured in much smaller quantities and that, for novel treatments, the development of a commercial manufacturing process is not guaranteed.
Such pressures have put the costs, risks and timelines associated with traditional batch-based development and manufacturing under scrutiny. In most industries, CM is seen as the low-cost solution to producing low value, high volume products in which there is little need to focus on the cost of materials used in process development and, often, little need for product changeover.
However, the opportunity to obtain more data from less product during development and eliminate the cost and risk of batch-based “scale-up” has inspired the introduction of small-scale, continuous equipment that can process small quantities of material during R&D while also being able to operate for variable lengths of time to match market demand during commercial production.
Regulators are increasingly supportive of CM and manufacturers are recognizing that current quality assurance costs are disproportionately large compared with other industries, wherein the production, detection and removal of out-of-specification product is vanishingly small. 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.
At GEA, we believe that continuous processing improves the quality of pharmaceutical end products: by focusing on quality during the whole product lifecycle, not just “tested in” quality; and by understanding the capability of your processes, managing sources of variability and decreasing any associated risks.
The ConsiGma™ continuous tableting line is a multipurpose platform that has been designed to transfer powder into coated tablets in development, pilot, clinical and production volumes in a single compact unit. The system can perform dosing and mixing of raw materials, wet or dry granulation, drying, tableting, coating and quality control, all in one line. By producing granules continuously, batch sizes are determined by how long you run the machine; and, because of ConsiGma™’s innovative design, the amount of waste produced during start-up and shut down is significantly reduced compared with conventional methods. Quality is measured throughout the process and, as such, drastically reduces the cost per tablet.
ConsiGma™ was developed in compliance with the FDA’s QbD initiative. It satisfies the industry’s need for reduced risk and higher quality while avoiding lengthy and costly validation and scale-up to bring products to market faster and cheaper. The inherent flexibility enables manufacturers to meet demand, keep expensive cleanroom space to a minimum and reduce inventory costs.
Integrated advanced process control and PAT tools enable monitoring during production, so quality can be designed into products from the start. ConsiGma™ provides maximum output in an energy efficient way, has been tested using more than 100 different formulations and is already being used by several large pharmaceutical companies, and ethical and generic research and manufacturing centres worldwide.