SIEMENS

Granulating, drying, grinding, mixing, and pressing — every batch of a medication, in the form of capsules or tablets, undergoes many different manufacturing steps in a predefined sequence. Unlike the processes in other sectors, manufacturing operations in the pharmaceutical industry are periodically interrupted in order to take samples, send them to labs, and have them checked for quality. This can take a long time, because each batch must remain in quarantine for up to two weeks as it awaits approval for the next production step. And if it’s determined that a drug’s homogeneity or active agent concentrations do not correspond to internal requirements, the whole manufacturing effort may turn out to have been in vain. The semifinished medications will then end up in the garbage.
This type of stop-and-go manufacturing is called batch production, and it’s standard in the pharmaceutical industry today. However, because it’s so drawn-out and fundamentally inefficient, regulatory agencies such as the U.S. Food & Drug Administration (FDA) have begun to look for alternatives. Their goal is to put in place systems that continuously monitor and control the quality of raw materials, process media, and intermediate products throughout the manufacturing process.
To this end, Siemens has developed a software system known as SIPAT (Siemens Process Analytical Technology). SIPAT can manage the traditional batch production process while also ensuring the prerequisites for continuous production. It does this with sensors that constantly evaluate the quality attributes of every batch. For example, it measures the even distribution of active agents and substrates in pharmaceutical mixtures through optical monitoring in real time. “The absorption and reflection of light rays tell us when the mixing process can be concluded,” explains Jürgen Manz from Siemens Industry Automation. “Regulations used to require that batches always be mixed for one hour — but now we can stop mixing a lot earlier if our sensors give us the O.K.”

Production Costs: Heading South. SIPAT is the centerpiece of continuous process control. It constantly calls up measurement values for parameters such as humidity, temperature, density, and the range of grain sizes. This enables the system to determine during production whether values are within the stipulated range and implement countermeasures in the event of deviations (closed loop control). In the worst case, a defective batch will have to be scrapped. “We save a lot of time because we no longer need to carry out complex lab analyses after each production step,” says Manz. “The production of a batch now takes only ten days instead of two months, and because there’s no longer any quarantine time, capacity utilization also increases.”
SIPAT reduces manufacturing costs for tablets and capsules by around 20 percent. It’s therefore no surprise that pharmaceutical companies like Merck and GlaxoSmithKline use the software for research and production.
The system can check the quality of each tablet, thus making it possible to completely retrace the manufacture of individual products. This means the Internet of things has now made its way into pill bottles as well, enabling digital product memory. Moreover, the large amount of data collected from each production plant gives pharmaceutical manufacturers valuable knowledge about their globally distributed processes. “Spectral data from optical sensors can be combined with mathematical models to calculate the quality of specific mixtures,” Manz explains. “Until now, such information about methods and models was available only locally at individual production sites. In the future, however, all of it will be stored in a central SIPAT database that will enable pharmaceutical companies to share the extensive resulting knowledge to further improve their products.”