What is the biggest advantage of coating with Continuous Manufacturing versus as a batch process?
Bertuzzi: Further to the time saving due to side operations, like loading and unloading, continuous coating results in general in better efficiency. In particular, energy saving due to less heat dispersion, saving in polymer to spray since losses are less with consequent maximum yield.
Dalmonte: You can divide the coating process into three parts: loading, coating and unloading. If you do a batch of 300 kilos, the total duration can be around four hours, where the coating itself is two hours. One hour is spent loading and another hour is spent unloading, and perhaps some time spend cleaning as well. If you take the same coating machine and make it continuous and do a 300-kilo run, you load the one time. So, you have the time of loading just the first time because then it’s a continuous process. You don’t spend any time unloading and you don’t spend any time for cleaning because you are not working in batch. If with a batch coater in one day you do the two batches which means 600 kilos. At the same time, with the continuous coating machine, you can do three times more production. This is the big advantage.
Are there advantages to Continuous Manufacturing for coating beyond speed and efficiency? Is the quality better?
Bertuzzi: Continuous coaters offer the opportunity to process tablets that are more delicate than usual, I mean with lower hardness, with logo, since the time the tablets spend in the coating pan, so-called residence time, is shorter.
Mechanical stress is less also because the tablets bed is thinner than in a batch coater.
Finally, Continuous Manufacturing unit operations are developed for the pharmaceutical industry to work under a Quality by Design approach, which means preventing possible issues or defects, that is speaking about coating discharging good tablets within the given specifications of either color uniformity or weight gain.
What are some variables associated with coating in a Continuous Manufacturing process?
Bertuzzi: The variables are exactly the same involved in batch coating: typically spray rate, tablet temperature and air flow. The main difference is the continuous flow of tablets.
In batch manufacturing, the tablets flow is generated by the speed of the pan and the batch size. In a continuous process, the tablet flow is generated by a feeder installed at the coater inlet and maintained constant by the drum speed.
Why do you think there’s resistance or reluctant for people to try Continuous Manufacturing?
Bertuzzi: Most of the reluctance is due to concerns about facing a new regulatory path and it is well known that the pharmaceutical industry has always been very conservative. Continuous Manufacturing from a regulatory perspective is still an emerging technology for which FDA are pushing for graduating it quickly to a standard one. With Thomas Processing we are pioneers; the first continuous coater was developed in 1993 to manage high production throughput of very large batch sizes of tablets to process in continuous mode. While at IMA Active, in Italy, we have recently designed Croma, a modular technology for continuous coating dedicated to small production throughput that can manage product development, clinical trials and manufacturing with one equipment size with no need of scale-up.
Dalmonte: There’s also an economic factor. Approaching a novel technology differently from what was used in conventional batch production, which is in place in the since many decades requires a great initial effort in the investments. All the companies already have batch processing machinery and established standards for quality control. Going through the change towards continuous manufacturing could mean a large initial investment either for machines or procedures.
What are some drivers of change?
Bertuzzi: For sure the support of regulatory bodies will facilitate the adoption of Continuous Manufacturing technologies. As mentioned before, the FDA have set up the Emerging Technology Program (ETP), which cooperate also with other international regulatory to harmonize and expedite the practice of continuous manufacturing in pharmaceutical industry. The FDA is putting a lot of energy and money to promote a change toward continuous manufacturing. FDA has just invested about $100 million just for training their people about emerging technologies. So, I think that is a significant hint to the pharmaceutical industry.
Are there upfront issues we need to be more aware of with continuous, like, for instance, formulation?
Bertuzzi: Concerning formulations, we highly recommend ready-to-use polymers available on the market that make the liquid film more stable and easier to manage, especially at high concentration. High concentration of the polymers in the coating solution enhances the performance of continuous coating. A higher concentration of solids in the solution means that the coating builds up faster on the tablet, and it maximizes the throughput of tablets you can achieve from the coater.
What other upfront issues as far as engineering or process design that you need to think of more so than batch processing?
Dalmonte: Consider that continuous process means, from an engineering point of view, completely changing the materials’ flow inside the manufacturing area, in favor of space reduction but with different materials-handling requirements. Rethinking completely the materials flow could be seen as an issue from an investment point of view but Continuous Manufacturing pushes industry to think lean manufacturing also to get a payback from daily costs of manufacturing later. Now that Thomas Processing is part of IMA Group, we are capable of providing our customer the ideal materials handling solutions as ancillary system of our CTC technology.
What sort of training or skills do people need to learn continuous manufacturing processes?
Bertuzzi: From our perspective, as equipment vendor, we can support education about Continuous Manufacturing and training of our customers with process experts at our respective laboratory trials either at Thomas Processing in Woburn and at IMA Active in Italy where pilot machines are installed. We also have capabilities to provide training service on site or remotely.
How do you ensure quality during Continuous Manufacturing?
Bertuzzi: A lot of our energies in R&D are dedicated to process control for CM. We count on a robust control system architecture based on a SCADA system and data management to support the Quality by Design approach required for continuous manufacturing. In addition, there are many PAT tools that pharmaceutical company can use to control the quality of the tablets when the coating process is in progress. We can install NIR or imaging sensors on our continuous coaters that can be helpful to read in real time the quality of the tablets.
What is the future of continuous manufacturing in coating?
Dalmonte: We do believe that continuous coating represents one of the first step to carry out by a pharmaceutical company as a transition towards Continuous Manufacturing. The new Accela CTC 500 we will be launching at Interphex in New York extends the capabilities of the industry standards.
Equipped with an advanced GMP design, it is the only coater manufactured with an integrated cooling chamber to reduce the overall footprint of the equipment and streamline the coating process.