PAT initiative speeds manufacturing, delivers consistent quality

In an effort to support innovation and efficiency in drug manufacturing, the U.S. Food and Drug Administration (FDA) introduced the Process Analytical Technology (PAT) initiative in 2003.

The PAT initiative aims to benefit the industry by supporting innovation and efficiency in the development, manufacturing and quality assurance of pharmaceuticals. Specifically, plants hope to see results by reducing production cycle times; preventing rejects, scrap and reprocessing of materials; increasing automation to improve operator safety and reduce human errors; and enabling real-time release.

Much of the initial work with PAT has focused on the development and application of analytical devices for timely measurements; however, it is only one aspect of the initiative. To fully address PAT's goal of achieving complete understanding and control of the manufacturing process, a wider variety of tools must be applied.

To integrate PAT into the overall scheme of process control and automation, there are various types of tools the FDA has identified, including:

  • Multivariate tools for design, data acquisition and analysis

  • Process analyzers

  • Process control tools

  • Continuous improvement and knowledge management tools

Using these tools allows manufacturers to focus on the five key elements of manufacturing: people, materials, facilities, equipment and documentation.

Additionally, by integrating these tools into the process control system, benefits such as faster development of new products, shorter manufacturing cycle times, higher yields, reduced waste materials, and fewer product recalls will be realized.

Successful Tools for PAT:

The foundation for the use of multivariate tools for design, and analysis leading to process improvement is reliable data. Industry tools are available that collect, store and replay historical plant process data. This makes timely information visible at the production level and throughout the enterprise. Access to timely data empowers plant staff to better align, plan, execute and improve business performance, which increases efficiency and translates to the overall goal of the PAT initiative.

With a foundation of reliable process data, multivariate analysis tools can be applied effectively. When selecting a multivariate tool, it's important to consider two factors: its ability to continuously monitor and quickly detect impending abnormal situations, and its ability to localize and identify the root cause of the impending events to allow a measured and appropriate response. It can be used for root cause analysis and the development of statistical models that identify cause and affect relationships to improve process understanding. Equally important, these models can be applied as part of a PAT control strategy to improve manufacturing performance by avoiding abnormal situations and reducing human errors.

Another tool that lends to the overall goal of PAT is the process analyzer. Process analyzers provide proven measurement and control solutions to keep plant operations running smoothly, efficiently and safely. An example of a process analyzer is the Laser Induced Fluorescence (LIF) sensor, a non-invasive device used to determine the homogeneity of dry powder blends.

The benefits of using an LIF correspond directly with the basis of the PAT initiative. This specific tool reduces the cycle time by eliminating off-line analysis and by defining a real end point that can be measured online. Quality assurance is also tracked through use of the LIF as well as rapid analysis.

Process control tools are an important element of a PAT solution. Process control tools help collect, synthesize and share process and business knowledge from multiple sources across the enterprise, and recommend appropriate actions so operators can increase their productivity. A more consistent operation through the application of automated control strategies, helps to prevent rejects and reduce human error.

Improvements to alarm system design can also lead to improved operator efficiency and decrease the amount of possible process upsets. Alarm management solutions help ensure that alarm systems perform effectively to protect uptime and safety operations by allowing operators to detect and correct process faults at an early stage. Other alarm management tools support PAT by offering functions that provide metrics of events and process history for root cause analysis of abnormal situations. Features that separate automatic notifications as low-priority alarms from true alarms are also valuable to alarm management. This feature permits the alarm system and operator to focus on alarms requiring immediate action.

These tools mentioned above are critical to ensuring that collected data are relevant and representative of process and product attributes, and allows the operator to be more effective. They directly address the reasons why the FDA launched PAT, to help the drug industry deliver higher quality products and improve the manufacturing process.

- Mark Albano