The pharmaceutical manufacturing landscape is evolving as never before. Much of this change is being driven by greater connectivity and the industrial Internet of Things (IIoT), making it easier to gather and analyze data and implement faster and more efficient manufacturing processes that produce higher quality goods at a reduced cost.
Fully compatible with and designed to enhance the US FDA’s Process Analytical Technology (PAT) program, one of the key pillars of GEA’s ConsiGma® 4.0 initiative is making continuous processing — and PAT — available to all. No matter what the size of the company or the scale of its applications, the company’s soft PAT solutions offer significant benefits, such as a temperature sensor in a fluid bed dryer, a loss-in-weight detector in a feeder or a torque detector in a twin-screw granulator.
“Monitoring parameters such as compression force and the thickness of tablets in a press, etc., a continuous line can be equipped to generate so many data points that the need for an expensive PAT probe is almost eliminated,” comments Cait Boyd, Sales Manager, Continuous Technology, GEA Pharma & Healthcare“You can correlate all the process information being created by the unit operations to confirm in real-time that you’re operating with in-specification material. This, in turn, makes it a more accessible technology to interested parties who may not have the experience or finance to be able to develop new/existing methods with a PAT probe.”
The fully integrated software system, Conductor 4.0, then helps to translate the information derived from soft PAT tools into meaningful data. Trend screens, for example, enable operators to identify any out-of-specification (OOS) occurrences (such as a feed rate varying too far from a set point), with the control system automatically sending a message to inspect the feeder or check the unit operation to prevent any loss of material or product. With the advent of Advanced Process Control (APC) procedures, the control system itself may actually be able to make the adjustment and streamline production very soon.
“PAT is a fully integrated and integral part of both ConsiGma® 4.0 and Industry 4.0,” adds Cait: “One of the key aspects of the latter is analytics, as well as being able to use tools to effectively generate meaningful data. With a PAT-enabled ConsiGma® continuous process, there is a significant volume of data coming off the line at any point in time. Second by second, more than 100 independent data points are produced from a variety of sensors and probes, providing loss-on-drying or blend uniformity updates, for instance. The upshot is that data is being generated constantly, and continuously, which absolutely aligns with the Big Data and analytics drivers of Industry 4.0.”
Compared with a traditional batch system, for example, wherein a loss-on-drying sensor would simply be used for endpoint detection (the entire 200 kg batch would reach a certain moisture content and the sensor would indicate that the process should terminate), one in a continuous granulation line feeds data back constantly regarding the condition of the material as it passes through the system (if good, the process continues and it progresses to the next stage; if bad, it’s rejected).
Specific to the pharmaceutical industry’s needs, GEA is also addressing the drug development phase with probes and PAT instruments to better design processes at an early stage. With advanced analytical tools and the ConsiGma® 4.0 R&D product line, QbD principles can be applied all the way from early stage product development through to commercial-scale manufacturing, enabling significant time savings and faster process transfers.
Data and information are produced in real-time, so researchers can see how the process is running and make any necessary adjustments to optimize the operational parameters. This also ties in to the production environment. If a process begins to fluctuate or start to go out of specification, they can adjust a specific parameter to overcome or prevent an issue occurring with the “batch.”
“Here,” notes Cait, “we have a lead into APC, which is very much facilitated by PAT to both optimize data acquisition and process control. For example, in a commercial-scale drug compression system, we have [blend uniformity] sensors that are used to simultaneously monitor the process and, if something goes OOS, send a signal to the tablet press and instruct the machine to reject the tablets being made until the conditions normalize. It’s adding a lot of extra functionalities to the equipment that we already have.”
“Of course, we currently work with Siemens and Perceptive Engineering so, if a customer wants to implement APC, it’s possible to liaise with those two companies and incorporate an established dashboard system for feed forward/feed backward control,” she says.
In conclusion, there’s a lot of opportunity for the greater pharmaceutical industry to develop more advanced processes, gain a deeper level of understanding of the operational parameters involved and, ultimately, make better products in a more cost- and time-efficient way.