Glossary Definition: Continuous Manufacturing (CM)

Continuous manufacturing (CM) is an end-to-end manufacturing process that enables products to be made without interruptions or pauses.

In existence since the 18th century, continuous manufacturing is the norm for certain industries, such as oil, automotive, and food processing. For other, more highly regulated industries like pharma, CM is less common, but is becoming increasingly popular in conjunction with technological advancements in artificial intelligence (AI) and robotics.

Continuous manufacturing is also known as: 

• Flow manufacturing
• Continuous flow manufacturing
• Continuous improvement manufacturing
• Continuous production 
• Endless production
• Constant production

Batch manufacturing involves stopping at the end of a batch yield to change hands, facilities, or equipment. This yield could be a drug substance that later goes as an entire "lot" to fill finish, or one that’s then processed into vials or other packaging for future consumption. Essentially, additional raw materials are not introduced during the batch run, so that the exact batch of material can be determined.

In contrast, continuous manufacturing proceeds without interruption until the product is finished. In pharma, this is difficult to achieve while still maintaining QA standards for the reasons outlined above.

In pharma, continuous manufacturing refers to the process of producing a drug from A to Z without interruption. This means there are no pauses, hold times, or facility or equipment changes. Instead, the entire production cycle involves a fully-integrated assembly line that automates every process, from start to finish.

Human input is ideally minimized with this method, but CM does occasionally require human intervention, such as when adding raw materials. However, humanless interaction is the goal, and in some rare cases such as Vertex’s Symdeko, it can be achieved.

Continuous manufacturing offers many potential benefits to pharma companies, including:

However, pharmaceutical manufacturers are still a long way off from harnessing the full power of these benefits.

While the potential benefits to CM are vast, it has been notoriously difficult to adopt and implement in the pharmaceutical space. The real challenge comes down to Quality Assurance (QA).

When a drug is released to market that can be audited or monitored post consumption for adverse events, a lot number or specific identifier is used to facilitate this process. In drug manufacturing, it’s necessary to specify exactly where a certain drug, fluid or particle was during the manufacturing process in order to determine exactly how the substance was harvested and yielded. In this way, it becomes possible to determine the exact specifications of the product that was consumed.

Continuous manufacturing makes this level of specificity very difficult to achieve. Think of a running sink, where the water is constantly flowing. That’s much harder to track than a series of five-second pours, right? Similarly, the ongoing nature of CM complicates the detailed tracking needed to ensure QA standards are met.

For these reasons, CM is still mostly a hypothetical in pharma to date. However, it has started to gain traction among the FDA and other regulatory bodies. In 2015, the FDA approved Orkambi, a treatment for cystic fibrosis, produced using continuous manufacturing. This groundbreaking approval — the first of its kind — continues to pave the way for other pharma companies to follow suit and adopt CM practices.

Continuous manufacturing is important for pharma because it offers companies a potential way to reduce costs, increase efficiencies, and scale drug production up or down based on market demand.

Although CM isn’t a viable option yet for most drugs, it’s becoming increasingly considered as a potential new avenue to streamline manufacturing while adhering to strict regulatory guidelines and ensuring drug purity. It’s also becoming more viable and accepted as a variant or portion of unit operations within batch processing as well. For example, processes such as filtration and chromatography are being adopted in a continuous sense, but the overall process may still be batched while the industry learns how to best manage, track, and report on such an operation.

As technology continues to advance, and equipment becomes cheaper and more accessible to pharma companies — especially smaller organizations — it’s possible that CM may become a viable standalone method for certain types of drug production.