Researchers target rapid changes to downstream continuous manufacturing
Today, many drugs are manufactured using batch processes that originated decades ago. This way of working features discrete processing steps, at the end of which equipment is emptied and cleaned ready for a new batch to start from scratch.
In contrast, continuous manufacturing is a nonstop process in which raw materials are fed in at one end and finished product comes out at the other. The potential for the approach to reduce costs and processing times while improving product quality has attracted the interest of regulatory agencies and manufacturers alike.
Early adopters of continuous manufacturing have realized efficiency gains. Janssen shortened its testing-to-release time by two-thirds when it started producing HIV drug Prezista (darunavir) on a continuous line.
However, there is scope to improve the process. Brettmann, an assistant professor at Georgia Tech’s School of Materials Science Engineering, is working toward this goal by applying her knowledge of the molecular-level behavior of materials to downstream processing.
“In continuous manufacturing you work with a lot of materials under flow, for example, so the requirements on the different binders that are used and the different processing aids that are used are a little bit different,” Brettmann told Outsourcing-Pharma.
The industry is still getting a handle on these differences. Manufacturers can draw on decades of knowledge when making decisions about batch processes but understanding of the requirements continuous manufacturing places on binder systems is still emerging.
This has implications for how quickly formulators can work toward optimal systems. Without a clear understanding of how polymer systems interact with drug molecules under flow, formulators must proceed by partly-informed trial and error when adapting products and processes.
Brettmann wants to give formulators tools and knowledge to facilitate faster changes.
“By studying how the materials interact at a molecular level and how that impacts the processing, we can rationally design the materials,” said Brettmann. “If you need to change to a drug molecule with different surface chemistry, we'll know ahead of time what type of polymer change needs to be made to adapt to that.”
Electrospinning drug products
Brettman’s interest in removing some of the roadblocks faced by teams working on the downstream side of continuous manufacturing has led her to explore two technologies that are new to the field.
Electrospinning, a way to make nanofiber mats loaded with active pharmaceutical ingredients (APIs), is the more advanced of the approaches. Brettman almost literally wrote the book on the pharma applications of electrospinning during her PhD at Massachusetts Institute of Technology and has continued to work on the approach over the subsequent years.
The work has advanced to the point that Brettman is talking to drug companies about the use of the approach, which could cut the number of steps needed to convert raw materials into finished dosage forms and increase the dissolution rate of the resulting finished products.
Brettman’s other project is further from commercial use. That project is exploring the use of 3D printing, either to enable production of small batches of personalized medicines or to bring manufacturing to locations where it is impossible to run large-scale operations.
The early-stage nature of the work means it will be some time before the approach achieves these goals, if it ever does. But the collective work of Brettman and her peers ensures the next generation of manufacturing innovations are already in the pipeline.