NeSSI and PAT Work Together in Pharmaceutical Manufacturing

The Center for Process Analytical Chemistry's New Sampling/Sensor Initiative (NeSSI) aims to reduce the footprint of analyzer systems. Thus, it complements Process Analytical Technology, potentially increasing analyzer up-time and providing more process information.

By David M. Simko, Swagelok Co.

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Cost is driving the increased use of process analytical chemistry instrumentation in all industries, including pharmaceutical manufacturing. One way that companies can improve quality and reduce operating costs is by controlling the chemistry of the process.

Process analytical instrumentation provides the measurement tools that provide the information that companies need to optimize their processes, ensure the safety of their employees, and meet appropriate mandated environmental regulations.

The FDA Process Analytical Technologies (PAT) Initiative encourages the use of innovative and readily available analytical tools to monitor and control the processes. For example, techniques and methods that operate on the basis of continuous interface with a reliable sample of the process fluid are being evaluated.

Pharmaceuticals are usually manufactured in batches, and laboratory test methods applied to samples extracted from the process are used to evaluate quality. The industry has relied on laboratory testing to resolve process, product, and quality issues for the last century. In off-line analysis, a sample is extracted from a sample point and physically transported to a laboratory where the analysis is completed using sophisticated and flexible measurement equipment. The PAT Initiative encourages manufacturers to supplement off-line analysis with a combination of at-line, on-line, in-line, and non-invasive analyses.

In at-line analysis, a sample is extracted from the process and transported to a dedicated analyzer located close to the process. On-line analysis employs an automated sampling system that extracts, transports, conditions, and delivers a sample to a clean and calibrated instrument and then disposes of the sample after the analysis is complete. Analysis may be intermittent, as in the case of a gas chromatograph, or continuous, as in the case of spectroscopic instruments. In-line analysis means that the analysis is carried out in situ using a probe equipped with a sensor that is inserted into the process. The advantage of non-invasive analysis is that no part of the instrument or probe contacts the process fluid, so the barrier between the process and the external environment is not compromised.

How Does PAT Enhance a Process?

PAT implementation calls for the right process analytical tools to monitor each critical product attribute in real time during the course of the process. A sensor must yield process fluid measurements that are reliable, repeatable, and validated. It is equally important to have process controls in place so that adjustments can be made based upon the analyses. Detecting and correcting errors, process deviations, or upsets while the process is moving forward can result in more efficient and tightly controlled process.

PAT implementation requires identifying the relevant technologies that can be applied to a specific process and product, as well as the use of effective data acquisition and management systems to handle the volume of data that will be generated. It also requires advanced automation concepts and techniques and tools, including intelligent devices that can communicate with each other and make appropriate repeatable, validated decisions without human intervention.

An integrated PAT system operating with the correct selection of analytical methods and technologies, sensors, and process controls can help ensure that the specified product quality will be achieved when the process is completed. It can reduce process cycle times, rejects and reprocessing, and scrap. It can utilize raw materials and energy more effectively and increase yield. In addition, the increased use of automation and process controls has the potential to improve operator safety, reduce human error, improve efficiency, and manage process variability. At statistically appropriate confidence levels, a PAT system may eliminate some finished product release testing. All of these results enhance the process and reduce manufacturing costs.

What is NeSSI?

The development of the concept of small smart sample and sensor systems began in the late 1990s in response to an industry-wide need to improve the performance of process analyzer sample systems. In the process industries, it was generally conceded that sample systems can account for as much as 80% of the problems with analyzer systems. In addition, while the analytical instruments, computers, and software had become more sophisticated, capable, and user friendly over the past 25 years, sample system technology had remained essentially unchanged.

In early 1999, the Center for Process Analytical Chemistry (CPAC) at the University of Washington became the forum for the end-user community to consider the possibilities for miniature modular sample systems. In late 1999, the Instrumentation, Systems and Automation (ISA) Society, through a subcommittee of SP76, Composition Analyzers, began an effort to develop a standard for an interface seal between a modular flow path substrate and necessary functional fluid control components.

A plenary paper presented at the 14th Forum on Process Analytical Chemistry (IFPAC) in January 2000, Process Analytical Systems: A Vision of the Future, by J.J. Gunnell and P. van Vuuren of ExxonMobil Chemical Co. addressed the costs associated with process analyzer systems and proposed rethinking the approaches to design, build, install, and operate them. They postulated that a savings of 40% of the total cost to build the systems could be achieved by reducing the cost of sampling systems, reducing the cost of sample transport, and eliminating the need for analyzer houses. They also estimated that a savings of 35% of the cost of ownership could be achieved by increasing the number of analyzers a technician could support, eliminating the need for a dedicated site analyzer engineer, and reducing the cost of the spares holdings.

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