PAT: A New Dawn for Drug Product Quality - Pharmaceutical Technology

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PAT: A New Dawn for Drug Product Quality
Leading experts share insight on the current and future direction of process analytical technology.


Pharmaceutical Technology
Volume 34, Issue 2


(PHOTO COURTESY OF MALVERN INSTRUMENTS)
Since the US Food and Drug Administration finalized its guidance on process analytical technology (PAT) in 2004, PAT tools and applications have evolved (1). FDA defines PAT as a "system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials with the goal of ensuring final product quality"(1). PAT tools may include multivariate data-acquisition and analysis tools, process analyzers or process analytical chemical tools, process and endpoint monitoring and control tools, and continuous improvement and knowledge-management tools (1). To gain a perspective on PAT in solid-dosage manufacturing, Angie Drakulich, managing editor, and Patricia Van Arnum, senior editor of Pharmaceutical Technology, gained the input of several industry experts. Todd Strother, applications scientist at ThermoFisher (Madison, WI) and Robert Mattes, application scientist at FOSS NIRSystems (Laurel, MD) discuss near-infrared (NIR) spectroscopy. Craig Dobbs, program manager of process analytics at Waters (Milford, MA), explains the use of ultra-performance liquid chromatography (UPLC). Alon Vaisman, application development manager for pharmaceuticals at Malvern Instruments (Westborough, MA), discusses the use of particle-size analysis. Tim Freeman, director of operations for Freeman Technology (Welland, UK), examines the use of powder-flow property PAT tools, and Janie Dubois, product manager for analytical imaging in the Americas at Malvern Instruments (West-borough, MA), discusses near-infrared chemical imaging (NIRCI).

Current applications

PharmTech: How are various techniques (e.g., NIR spectroscopy, UPLC, and particle-size analysis) currently used as a PAT tool in solid-dosage manufacturing and by your company specifically?

Strother (NIR spectroscopy): Our Antaris NIR systems are an integral tool for PAT in pharmaceutical and solid-dosage manufacturing from raw-material analysis, to intermediate formulations, to analysis of the final products and tablets. First, the systems are used on the receiving dock to verify the material being brought in is correctly identified and of the quality needed. Good-quality NIR systems are robust enough to withstand the abuses that might be found on the loading dock, including extremes of temperature and humidity as well as vibrations from equipment. The technique is suitable for these conditions and can produce usable data right there on the loading dock without taking samples back to the laboratory for more labor-intensive analysis.


Dynamic powder characterization using the Freeman Technology FT4 Powder Rheometer. (Courtesy Freeman Technology)
NIR also has been found to be highly valuable throughout the formulation process. Small portable units such as our Target systems are fitted onto powder blenders to determine when blending is complete and to guard against overblending, which will ruin a batch and cost a substantial amount of money. These units will typically communicate their data wirelessly and draw their power from rechargeable battery packs or slip rings. Other areas in the process can be monitored on-line or in-line in real time, including batch reactors, storage tanks, dryers, and even pipe lines. NIR light is easily ported through many meters of fiber-optic cables and probes to access areas that challenge other techniques. This ability, of course, allows every aspect of the process stream to be monitored and ultimately controlled for deviations in the process. High-quality and well-utilized systems can interface with process-control software to automatically set off alarms, open valves, or add components at precise times to make sure the manufacturing process behaves properly.

NIR is an exceptionally good tool to nondestructively monitor the quality of the final solid-dosage form. The light can penetrate deeply into and through most tablets to determine total amounts of the active pharmaceutical ingredient (API). Transmission-type measurements collect this NIR light that travels through the solid forms and provide information on the internal materials while reflection-type measurements provide information on tablet coatings and thicknesses. All of this can be done automatically and nondestructively


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