How Continuous Manufacturing is shaping the future of the industry
When the FDA issued its Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance in 2004, the intention was to drive the pharmaceutical industry into an era focused on patient safety enhancing the quality of the product and the efficiency of the process, also encouraging increased sustainability. This opened the door to emerging technologies. Since then, the crux of the matter has been to adopt a QbD (Quality by Design) approach to the manufacturing process using principles of engineering, material science and quality assurance to ensure acceptable and reproducible product quality and performance throughout a product’s lifecycle. What is quite clear to the regulatory authorities, still nowadays, is that many drug recalls and shortage issues are due to unacceptable product quality related to manufacturing problems. This prompted the FDA to foster the “Advancement of Emerging Technology Applications for Pharmaceutical Innovation and Modernization”. The challenge of meeting urgent demands for more new medical products during the COVID-19 pandemic has highlighted the value of more responsive and flexible manufacturing methods, including lines of equipment that can be easily installed and scaled up in combination with automated processes.
First step: Continuous Manufacturing
Identiﬁed by FDA as the ﬁrst step in a trend of emerging technologies whose ultimate objective was to ensure failsafe quality and at the same time improve production eﬃciency, Continuous Manufacturing is now under the spotlight more than ever before. The FDA underlines the importance of having a clear understanding of the speciﬁc processes and technologies used to manufacture drugs throughout their lifecycle in order to ensure the quality and safety of pharmaceuticals, adding that this starts before a product is even approved and brought to market. In the meanwhile, international regulatory authorities support international harmonisation of guidelines to advance Continuous Manufacturing operations for drug substances and drug products around the world, as seen in the new Q13 guidance developed by the International Council for Harmonisation (ICH). This ICH initiative aims to advance product quality through operations that reduce manual handling that leads to human error, utilize online monitoring and controls, manage data, increase manufacturing throughput and eﬃciency, and install smaller equipment. Cost-cutting initiatives are also addressed.
The Continuous Manufacturing journey: IMA Active’s role in accompanying the industry towards the next evolution
IMA Active’s belief in and knowledge of Continuous Manufacturing have grown stronger thanks to a smart multidisciplinary team in R&D and intensive work carried out on two fronts. A more disruptive front of our R&D consists in the partnership with CONTINUUS Pharmaceuticals, a spin out of Novartis MIT centre, leveraging a novel production platform called Integrated Continuous Manufacturing (ICM). ICM enable seamless end-to-end production of small-molecule drugs that incorporate API formation steps with ﬁnal drug product formulation. Within the ICM project, we support the development of Extrusion Molding Coating (EMC), a highly innovative technology for making oral solid dosage forms, using our coating expertise and equipment design capabilities. All started about 8 years ago and nowadays CONTINUUS Pharmaceuticals is building their ﬁrst GMP facility for injectable and oral solid forms in Massachusetts.
While on the other front we work on continuous processes by revisiting current technologies, embracing a concept of Continuous Manufacturing more closely related to conventional batch processes. This initiative aims primarily at introducing continuous equipment that can be integrated in existing plants, also adopting hybrid control strategies in order to improve the production performance of existing drugs. With a range of machines that are more than ready for Continuous Manufacturing, our key role today is that of enabling our customers to achieve high product quality and production eﬃciency by understanding the mechanisms involved in implementing the most suitable process.
Process engineering and Process Analytical Technology are areas of competence where we have invested and grown to provide a signiﬁcant contribution for our customers towards the development of modern manufacturing. Integrating these disciplines with our broad experience in equipment design and advanced automation, we leverage our expertise, matching cutting-edge technologies and machines featuring advanced integrated control systems with in-depth process knowledge and a model-based control strategy.
MAESTRO: how integrated control systems maximise quality and efficiency
MAESTRO represents the core for IMA Active’s journey towards Continuous Manufacturing. It is our integrated control system able to orchestrate all the unit operations of a Continuous Manufacturing line. MAESTRO completes our project to harmonise HMIs and Scada systems which enhance user experience in a modern digital factory. We have worked bringing a breadth of knowledge, skills and capabilities to translate the operational requirements into a robust, ﬂexible and eﬀective automation system. The technological basis of MAESTRO focuses on modular architecture, data management for built-in controlled quality and maximum performance.
Continuous processes require precise control, reliable monitoring of critical parameters to ensure quality attributes, and accurate collection and aggregation of data to produce the proper documentation. The platform’s design faces today’s demands, not only for an advanced level of control strategy, but also for usability, ﬂexibility, reliability, and connectivity.
IMA Active is driving the evolution
We are now able to supply a fully integrated line for direct compression of coated tablets or unit operations to combine with maximum ﬂexibility as part of new or existing plants, as a single supplier of complete integrated solutions based on ﬂexibility and modularity. At the IMA Active Laboratories, we enable customers to test their own products comparing a batch process to a continuous one.
CDC: lean and flexible technology to make tablets
CDC is a pharmaceutical manufacturing process that has just graduated by the FDA’s Emerging Technology Program (ETP). It consists of dispensing materials, mixing them together, and compressing the blend to form tablets using equipment that is integrated together, resulting in no breaks in the process. CDC oﬀers ﬂexible scale-up approaches by operating the process for longer periods of time that can better meet changes in product demand. CDC has a minimal footprint and also minimizes the need for human interventions with the process, taking advantage of Process Analytical Technology (PAT) both of which can improve the assurance of product quality.
CROMA: innovative technology for continuous film coating of tablets
CROMA continuous coater is our novel technology for fast and truly continuous tablet coating. It is a modular unit operation that can be conﬁgured as a single module or as a combination of more modules, either in series or in parallel. Such combinations allow companies to produce coated tablets at diﬀerent throughputs or coating weight gain. CROMA can actually work in truly continuously, but also batch modes. This means it can be used either for product development or production with no need of scale-up.
Product Manager for process equipment at IMA Active