71 TWENTYFOURSEVENBIOPHARMA Issue 1 / March 2025 ENZENE A decade ago, continuous manufacturing was making waves in small-molecule drug production. In 2015, Janssen (J&J) secured regulatory approval for Prezista®, a milestone that demonstrated CM’s viability for pharmaceuticals. It was a game-changer—real-time release testing, in-line monitoring, and predictive analytics became industry talking points. But biologics were a different story. Back then, batch processing dominated biologics, producing just a few grams per liter—a fraction of today’s yields. Unlike small molecules, biologics require complex cell-based production, making CM adoption much tougher. The industry faced two big hurdles: the technical challenge of linking upstream and downstream processes and regulatory uncertainty about how to oversee continuous systems. Through the late 2010s, key innovations helped bridge the gap. The rise of single-use bioreactors lowered upfront investment costs, making it easier for manufacturers to scale biologics production. Regulatory agencies, once hesitant, gained confidence in CM, particularly as smallmolecule successes mounted. The complexity of large-molecule drugs meant that any deviation in production could have profound consequences. However, frameworks such as the Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q8, introduced in 2008, established the principle that process design should be intrinsically linked to product performance. Around the same time, biosimilars took off, further driving demand for cost-effective manufacturing. In 2015, the FDA approved the first U.S. biosimilar. The FDA streamlined biosimilar approvals and guidance on interchangeability requirements which made continuous manufacturing an increasingly attractive option. With biosimilar approvals growing—59 since 2015—the industry now recognises that fullyconnected continuous systems offer a path to not only cost reduction but also improved product consistency. International regulatory bodies such as the ICH have in fact developed specific guidelines, like ICH Q13 now, to assist drug manufacturers in implementing CM for both drug substances and products. What has really made a significant mark towards the success of CM technology is the real-time monitoring using Near Infrared Raman (NIR) spectroscopy and Process Analytical Technology (PAT). These enable manufacturers to observe and fine-tune production parameters in real time, ensuring consistent quality throughout the process. Meanwhile, computational tools such as quantum computing and support vector machines have advanced chemometric modeling, boosting the reliability and accuracy of real-time testing. This combination of inline testing, predictive analytics, and cutting-edge data analysis has made real-time release testing more dependable and efficient than ever. Currently we are seeing around 8-10g/L in batch processing—a dramatic increase from 5g/L as industry standard a decade ago, and so CM for biologics is at a turning point. Regulators have clearer guidelines, manufacturers have better tools, and market demand is higher than ever. The industry is finally poised to take full advantage of CM, making biologics production more scalable, cost-effective, and efficient. Enzene entered the market a few years ago with an aim to make cost effective biosmilars in India.
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