Imagine mixing the ingredients to make a batch of cookies. First, mix the dry ingredients: flour, baking soda and salt. Second, mix the wet ingredients: butter, sugar, vanilla and eggs. Finally, mix the two batches together and then scoop out individual portions to bake. After the timer rings, the cookies are pulled from the oven and begin to cool; they look perfect and delicious. But as soon as you take the first bite, that smile turns into a frown. It’s a “bad cookie” and it tastes like a salt lick. The entire batch is ruined. Just think, if one had the ability to make each cookie individually, then the “bad cookie” might have been detected earlier and the “baker” could have fixed the recipe, so the entire batch would not be ruined. Sound familiar? It should, because this is the approach that universities and the pharmaceutical industry are validating for tablet production. Instead of making gigantic batches of medication that require months to process and release, pharmaceutical manufacturers are taking their cues from the food and fine chemical industries, making tablets from a linear process continuum that supports real time release, reducing the production time by more than 90 percent. Known as “Continuous Manufacturing” the method is being recognized for its efficiency and cost and quality control attributes.
At the forefront of the continuous manufacturing research and development is Rutgers University. Early on, Siemens formed a relationship with Rutgers to help the pharmaceutical industry move forward, to push the envelope and modernize pharmaceutical manufacturing and dosage forms for a more efficient future. The foundation of this relationship is built on Siemens membership in the Center for Structured Organic Particulate Systems (C-SOPS).
Rutgers is C-SOPS’ academic leader and is joined by other university participants including Purdue, New Jersey Institute of Technology, and the University of Puerto Rico. Additionally, more than 40 companies are involved in supplying technology, training, mentorship, and product testing. The mission for C-SOPS is to develop a structured design, engineering, scaling, optimizing, and control process to manufacture tablets and effectively educate companies on how to adopt and test these efforts.
The ascertainable impact of this effort is to provide a science based and neutral ground to deliver a proof of concept that will enable and promote the transition from batch processing to continuous manufacturing in the pharmaceutical industry. This test ground is designed to help pharmaceutical companies show proof of concept for continuous manufacturing to the FDA, in order to aid them in acquiring FDA regulation approvals. In February 2013, Rutgers opened a full-scale continuous manufacturing production line on its campus. The research facility allows pharmaceutical producers to conduct performance and feasibility testing for the multiple production paths in continuous manufacturing. At the time of this article, the production line had been running only nine months; nevertheless, a great deal of research and development progress has already been made thanks to advanced process control and automating processes that improve efficiencies.
SIEMENS TECHNOLOGY CONTRIBUTION
Siemens donated its SIPAT data management system, a platform that manages enormous amounts of data, and PCS 7, a distributed control system (DCS) that controls the production line with integrated libraries, preconfigured standard blocks and faceplates. In addition to control, the DCS provides transparency to the process and enables optimization of the manufacturing line’s performance to Rutgers University. Additionally, Siemens provided on-site training to get the research team up to speed on how to use the technologies and the research team has access to a full-service support line for ongoing questions. The Associate Director for Industry Relations for C-SOPS at Rutgers, Doug Hausner, shared with Siemens that the benefit of using both of these technologies concurrently is that they “work seamlessly together.”
During the continuous manufacturing process, a large amount of data is collected, adding up to 4,000 data points every 1.5 seconds. SIPAT not only gathers this data accurately, it normalizes the data into a common timeline so technicians can make sense of the bombardment of information in order to execute decisions in real time. For example, when testing powder blends, which are eventually molded into tablets, the data management technology understands precisely when a blend is fully mixed, to ensure the medication is made to spec. If an error does occur in the mixing process, the SIPAT technology alerts the technician and the technology will automatically discard the ruined tablets, without wasting an entire batch. Additionally, if a variable needs to be adjusted to maintain product quality, such as changing the percentage of ingredients to the mix, advanced feedback control is utilized.
Compare it to the task of baking a cake. SIPAT technology ensures that all the sugar doesn’t end up in just one piece of the cake and that it’s distributed evenly throughout the entire cake. If for some reason a couple of slices were produced without any sugar, the system would place them in the waste basket automatically, in real time.
Ph.D. student, Abhishek Sahay, who interfaces directly with the SIPAT technology, pointed out a number of advantages that the Siemens technology provides him and his team in their continuous manufacturing research. First off, SIPAT enables them flexibility to make agile changes at different stages of the manufacturing process, enabling them to get the system up and running quicker because of the ability to adjust parameters along the line faster. Additionally, without SIPAT, technicians would have to interface with multiple separately operated interfaces which take time and specific training. SIPAT eliminates the time it takes to manage individual interfaces because the technician only has to use one, and that’s SIPAT.