Batch processing has been the standard manufacturing method used by the pharma industry for the last 50 years. But recent advances in manufacturing technology have resulted in a faster, more efficient process known as continuous manufacturing. How do the two processes compare? And what are regulators saying?
The Food and Drug Administration (FDA) describes continuous manufacturing as “one of today’s most important tools for modernizing the pharmaceutical industry,” has recommended its use and recently issued draft guidance about the quality considerations for continuous manufacturing1. However, industry experts are divided between believing that regulatory agencies should allow the industry the freedom to innovate in the manufacturing space and believing that regulatory support of continuous manufacturing will increase its adoption and therefore its benefits in the industry.
The move from batch processing
For more than 50 years, pharmaceuticals have been produced using batch processing/manufacturing, a multi-step production process in which each stage must be completed before the next can begin. This is an inherently lengthy process, which is further compounded by the “hold times” between steps for quality testing or shipping of material between facilities for the next step in the process. This time-consuming process places environmentally sensitive ingredients at risk of degradation, and the multiple handling points introduce risks of contamination and human error.
In an effort to improve the efficiency and quality of drug production, many analysts and drug regulators have suggested continuous manufacturing, already widely used in other industries, as an alternative drug production process.
Regulatory support of continuous manufacturing
Recent advances in manufacturing technology have prompted regulatory agencies to seriously consider the faster, more efficient process of continuous manufacturing, which could not only improve product quality but also mitigate the underlying causes of drug shortages and recalls. Continuous manufacturing moves pharmaceuticals nonstop within the same facility – eliminating hold times, reducing the likelihood for human error, ensuring consistent quality and enabling faster responses to market changes through flexible run times.
The FDA views modern manufacturing processes such as continuous manufacturing as key to its strategic efforts to reduce the number of drug shortages. It also considers advanced manufacturing processes as important for public health emergency preparedness and response, owing to their shorter supply chains, greater resilience to disruption and ability to rapidly produce vaccines and scale production, if needed, in response to ongoing outbreaks.
In February 2019, the FDA issued draft guidance outlining the quality considerations for the continuous manufacturing of drug products. In it, the agency voiced its support for the continuous manufacturing of drug substances and all finished dosage forms submitted in new drug applications (NDAs), abbreviated new drug applications (ANDAs), drug master files (DMFs), biologics license applications (BLAs) and nonapplication over-the-counter (OTC) products. In addition, the International Council for Harmonisation (ICH) is drafting guidance, “Q13 Continuous Manufacturing of Drug Substances and Drug Products (adoption of final guidance expected November 2021).”
With the ability to monitor product quality in real-time, continuous manufacturing also aligns with the FDA’s quality by design (QbD) initiative. Furthermore, in its guidance on continuous manufacturing, the FDA states that the “operational flexibility may decrease the need for some post-approval regulatory submissions.”
Industry’s view of continuous manufacturing
As margins continue to decrease, continuous manufacturing offers pharmaceutical companies the benefits of reduced costs, risks and timelines. Transitioning to continuous manufacturing could bring higher yields, a smaller footprint, lower energy consumption, consistent production, agility and reduced waste.
Despite these potential benefits, the transition to continuous manufacturing has been slow for several reasons. First, start-up costs can be high as companies would need to retire old equipment, purchase new equipment, train staff and update the surrounding infrastructure. Some companies also have doubts about the ability of continuous manufacturing to handle anything but large volumes of low-cost drugs. For small-batch products, significant cleaning and setup time would be required during the changeover.
Analysts, regulators and industry leaders agree that continuous manufacturing is the future of drug production. As with any disruptive technology, the early stages of implementation will be resource-intensive.
To learn more about how to efficiently transition to continuous manufacturing, watch our webinar, “The future of continuous manufacturing in pharma.”