Modular system answers PAT requirements

The potential of the system in the pharmaceutical industry was presented at last month's Interphex exhibition in New York by David Simko of Swagelok, one of a number of companies and organisations in the NeSSI (New Sampling/Sensor Initiative) consortium, the brainchild of the Centre for Process Analytical Chemistry (CPAC) in the US.

The PAT initiative - which involves the use of in-process measurements to improve the quality of production processes, boost yields and reduce wastage - was unveiled by the FDA in October 2004. The document served as a call to arms for the drug industry to improve its manufacturing processes, which have undergone little evolution over the last few decades, as well as an assurance that the agency was prepared to be more accommodating in reviewing changes to manufacturing processes. Before the PAT initiative came out, companies faced a considerable burden in proving that changes to a process did not result in any changes in product quality.

In essence, a system aiming to deliver PAT involves a sampling mechanism and a series of analysers that can take data and convert it into information on the spot, said Simko. This information should then be fed to another device, which can adjust the process accordingly and keep a record of the adjustment that was made.

This is very different to the current approach used in most pharmaceutical production environments, he noted. At present, most pharma manufacturing is a batch process, with analysis carried out by taking a sample from the reactor container and sending it off to the laboratory. This is in stark contrast to the petrochemical and even food industries, where at-line analysis (where sampling and measurements occur on the production line) and on-line/in-line analysis (continuous monitoring) are commonplace.

Small is beautiful - and necessary​

NeSSI has developed a series of standardised, modular components that bolt together and provide many of the fluid handing and sensor technologies that are needed in a pharmaceutical processing environment, according to Simko.

But one key element that has needed to be addressed is miniaturisation, mainly because any PAT system will need to run equally well in pilot scale as in production scale, but also because smaller sampling volumes can sped up the process and reduce wastage.

Swagelok has developed a standardised fluid handling system that can be configured by joining individual modules together. Sensor devices clamp on top of the fluid handling modules - known as the substrate. The aim is that companies will agree on this standard, so that a customised system of linked sensors can be inserted into any production process.

Other members of the NeSSI consortium are already coming up with sensors to fit on this standard substrate bed. For example, Parametrics has developed oxygen and water probes, the likes of Bruker, Porter and Brooks offer mass flow meters, and other suppliers are developing near-infrared (NIR) analysers, Raman probes, pH meters and conductivity readers that can all be configured to the platform. Siemens has a tiny chromatograph, just 8 inches high, that could also be incorporated into this type of system, noted Simko.

The first generation of NeSSI devices, which carry out relatively simple fluid handling and analysis functions, are already installed in a number of facilities and have proved to be robust, i.e. they are not subject to leakage or vibration that could interfere with the process. One application of the technology has been a carrier module for gas chromatography, which has carved the running costs of the unit by $1,000 a year - a saving that could be significant in labs running multiple GCs simultaneously, noted Simko.

"Modular concepts can be applied as platforms for chromatographic, spectrographic and electrochemical techniques for liquid and gas systems,"​ said Simko, adding that both physical and chemical sensing is feasible, with potential even in mixing applications.

The next generation, with intelligence added at the device level, are currently in development, while thoughts are already turning to the third generation. In time, said Simko, these devices are likely to offer additional functionality such as wireless communications that will make them even easier to install and operate, although he noted that wireless security issues need to be sorted out before they can become widely adopted. These systems should be available within the next year or two.

He told In-PharmaTechnologist.com that while pharma applications of the NeSSI systems are still very much at the development stage, Swagelok and other consortium members are talking with several drug companies interested in evaluating the technology.