Continuous manufacturing (CM) of drug products in general, for a variety of reasons and despite its potential advantages, is still very much a delayed promise. On the other hand, CM of drugs has been around for many decades and this is easily explained by the different paradigms of production, especially in what concerns specialization and volumes. CM is typically associated with the production of large volumes of products. In particular, small molecules with therapeutic activity, resourcing to chemical or biochemical routes, are often produced in continuous mode, not just in the synthesis, but also in the downstream process. Commonly, industrial sites that manufacture pharmaceutical drugs (APIs) are often specialized in a limited portfolio of products that are produced in large amounts, whereas laboratories that formulate drug products tend to produce more products and smaller volumes. Consequently, the adoption of CM for drug products has not been considered seriously until very recently. Technology and regulation are now steering the drug products industry towards the adoption of other manufacturing paradigms than the traditional batch or semi-continuous mode (e.g. CM or additive manufacturing). Agencies like FDA, EMA, MHLW followed by the ICH have been issuing quality guidelines addressing important aspects of medicines’ quality and fostering the incorporation of more knowledge into the drug development pipeline. Consequently, this effort in deepening all scientific aspects of medicines’ development opens new opportunities, namely in the context of manufacturing and improved life cycle management of marketed products. In consequence, it is no longer a distant possibility to opt for continuous instead of batch processing when manufacturing even conventional pharmaceutical forms such as tablets.
Why move to continuous?
Simply because technological and regulatory barriers are no longer a threat (check for instance the ICH Q13 guideline on CM), and CM offers a few interesting advantages. Being able to produce batches of variable dimensions according to commercial needs, using significantly less energy resources, in much smaller facilities, in a more timely manner, requiring less manpower, lower ecological fingerprint, minimizing failure occurrence, increasing quality control standards with increased flexibility are only a few advantages of CM. These translate into economic benefits for the manufacturer and increased safety for the patients. Additionally, CM is more able to cope with personalized and individualized medicine manufacturing requirements, which are paving the way toward new paradigms of interaction between health professionals (including pharmacists) and patients. Of course, this is only possible with the recent advances in technology (equipment and analytical devices for real-time quality control) and a favorable regulatory environment (e.g. quality-by-design). In-process control analytical devices able to track materials attributes in-situ and in real-time are also indispensable allowing CM processes to be efficiently controlled. Probably the major bottleneck now is the lack of trained professionals, pharmacists, engineers, chemists… that can efficiently develop, validate and maintain CM systems working.