Increasing Process Robustness and Flexibility with Integrated Continuous Manufacturing

For decades, pharmaceutical manufacturing did not evolve as other industries did. Process technologies largely remained the same, and innovation, while almost unbridled in drug discovery, was subordinated to established processes with minimal disruptive risks. But the risk of stagnation caught up with the industry, as outdated production systems failed quality requirements and revealed gross lead-time and cost inefficiencies. Fortunately, many drug manufacturers are now pivoting, some exploring how continuous manufacturing can lead to a paradigm more closely aligned with the expectations of regulators and consumers. The former have supported this movement, providing direction through draft guidance and regulations. One major advantage associated with this more advanced manufacturing method is the increased robustness it offers. For example, with continuous manufacturing, real-time monitoring of critical process parameters allows for immediate correction of process deviations, enabling a state of control. Conversely, with the current batch system, manufacturers rely on off-line tests that indicate whether a batch of material, usually large in quantity, meets specifications. These results are usually only available after the fact. Flexibility is another important consideration. Continuous unit operations are flexible and modular, and can be easily and quickly reconfigured to produce different drug products. Furthermore, their dial-up and dial-down capability enable production to adjust instantaneously to changes in demand. In this way, patient access can be improved, while maintaining a lean supply chain. The speaker will discuss these aspects of continuous manufacturing, along with other factors, focusing on Integrated Continuous Manufacturing (ICM), a strategy that integrates both upstream drug substance and downstream drug product manufacturing components into a single seamless process. Implementation challenges and potential solutions will also be explored.