As drugmakers look to optimize manufacturing processes to meet demand for new and complex drugs, as well as combat record high drug shortages, some experts are pointing to a production method that could help tackle these dueling challenges: continuous manufacturing.
The manufacturing method, which relies on continuously inputting materials into the production process, has been used in other industries like food for decades. Yet the pharmaceutical industry hasn’t quite caught up yet. Some in the sector, however, say that could change as more companies see the method’s merits.
What is continuous manufacturing?
Continuous manufacturing is an “advanced manufacturing technology where input materials are continuously fed into production and transformed, and processed output materials are continuously removed,” according to the Food and Drug Administration.
In the drug manufacturing world, it means production lines running 24/7, uninterrupted.
This constant input has multiple benefits for manufacturers — including the need for less inventory storage space, more real-time data points and improved time to market compared to traditional batch manufacturing, according to Kevin Bittorf, senior executive and consultant for pharmaceutical manufacturing at SCX CMC Solutions.
Continuous manufacturing can all be performed in one space, which reduces inventory and storage needs because it produces items without breaks between batches.
“Where batch manufacturing, you have more physical storage because you're waiting for release time before it goes out. You're storing more raw materials,” Bittorf said.
Batch manufacturing involves a series of steps that require multiple rooms for different stages of production, resulting in more monitoring, manpower and a lengthier end-to-end process. After each step in the batch process, additional tasks must be completed, such as moving materials to a different site, conducting quality checks or reviewing equipment.
Currently, continuous drug manufacturing is best for making small molecule capsules, tablets and oral solid dose products, usually in larger volumes, Bittorf said.
What roles do AI and automation play in continuous manufacturing?
Manufacturing continuously provides access to thousands of additional data points, which can be used to analyze and improve processes in real-time.
“The disadvantage for continuous manufacturing is you have to track each component," Bittorf said. "Knowing where each component is when you introduce it, the timestamp of that and ensuring that you have an idea of where and when each component was inputted into the system."
Any added costs driven by the need for more data storage are outweighed by the long-term benefits to production efficiency, he added.
“You have more data, that's more expensive, but you might be able to store less. You have less material losses because you don't need as much sampling. You have less startup and shutdown costs because you're running less, so you save more material overall,” Bittorf said.
The focus for drugmakers should be on what they do with all the data once they have it, which calls for a more technically skilled labor pool to help with the advanced automation and data upkeep, according to Doug Hausner, senior manager of business development continuous manufacturing at Thermo Fisher Scientific.
“The hard part is getting that all established. So getting all those systems in place, making sure everything works," Hausner said in an email. "It's a lot of frontloaded effort, as far as people and time to get everything set up to then allow it to run smoothly for long periods of time without a lot of intervention or support."
Why the pharma industry has been slow to respond
Continuous manufacturing in the pharmaceutical industry has been slowly growing for about a decade, according to Bittorf. Yet it’s a process more embraced in other sectors like steelmaking, food and auto, while drugmakers have been more hesitant.
“One of the challenges for pharma has been the culture and ability to adopt new things in a highly regulated environment.”
Doug Hausner
Senior manager of business development continuous manufacturing at Thermo Fisher Scientific
One reason for that could be because continuous manufacturing is a more expensive option, with upfront costs for advanced equipment and data storage, Bittorf said.
The industry must also navigate more FDA approvals at multiple stages of development, production and distribution.
“One of the challenges for pharma has been the culture and ability to adopt new things in a highly regulated environment,” Hausner said.
Another hurdle is that FDA approval is needed if a company wants to change its existing manufacturing process to continuous, meaning it’s smarter to start from the beginning of a new drug's manufacturing process, rather than after a drug has completed multiple trial phases, Hausner added.
“If I already have an existing product in market, there's much less benefit to switch the manufacturing process. You have to pay for the capital and the other things that go with change and you have to resubmit that," Hausner said. "Most of the interest is in using the technology for bringing new products to market."
Signs of continuous manufacturing adoption in the industry
While regulatory hurdles exist, the federal government is pushing drug companies to adopt the process.
In 2021, the House of Representatives passed a bill that would direct the FDA to designate up to five national centers of excellence in advanced and continuous manufacturing. The same year, the Department of Defense awarded $69.3 million to Continuus Pharmaceuticals to develop continuous manufacturing capabilities for critical medicines.
The FDA has been on board too, performing an audit in 2022 that compared batch manufacturing to continuous to compare federal approval and market entry speeds. Continuous manufacturing outperformed batch on both fronts.
“FDA encourages the utilization of CM for the development and manufacturing of drug substances and finished drug products,” the agency said in the audit report.
While a slower uptick than other industries, the adoption of the process is creating change throughout the drug supply chain.
“It’s being adopted, and this can be seen through the investments equipment providers have publicly announced to meet demand for their continuous manufacturing equipment. These are being purchased by branded companies who are bringing pipeline products through using continuous manufacturing technology,” Hausner said.
Major contract drug manufacturers are also taking note of continuous manufacturing's potential.
Thermo Fisher Scientific operates a continuous manufacturing line at its Greenville, North Carolina, facility, according to Hausner. The company has four active continuous manufacturing oral solid dose programs and is planning for two commercial programs in 2026.
Pfizer has two facilities completely dedicated to CM in Groton, Connecticut, and Freiburg, Germany. The company estimates that 70% of its small molecule, solid oral dose portfolio will be made using its continuous manufacturing process within the next ten years.
Yet Hausner and Bittorf both note that not all manufacturers should adopt the newer technology right away. They must evaluate the costs, product volume, future scaling and technical feasibility of the available equipment and facility for producing drug products.
“It’s not a simple question — comes down to program-specific benefits,” Hausner said.
Bittorf hopes that in the next five to 10 years, more companies shift away from seeing continuous manufacturing as a burden to implement.
“Right now, a lot of companies are ‘I'm worried about going into continuous manufacturing because I think there's this regulatory hurdle, there's not enough equipment out there’ and I just want it to be looked at as ‘I have a choice on how to manufacture my product. How do I want to do it and what's the best way for my product?’” Bittorf said.
