Process analytical technology monitoring

The FDA also introduces the concept of process analytical technology (PAT). PAT refers to systems that are used to analyze, monitor, and control manufacturing processes on a continuous basis. The quality attributes and specifications of raw materials, in-process intermediates, and processes are measured in real time and compared with predetermined parameters so that deviations can be rectified in a proactive nature to assure that the end products conform to the level of quality as expected. It is believed that a system based on PAT being implemented in a real-time manner would improve manufacturing efficiency and simultaneously retain or improve the product quality through these interactive measurements and controls. 

T.R.M. De Beer, W.R.G. Baeyens, J. Ouyang, C. Vervaet and J.R Remon, Raman spectroscopy as a process analytical technology tool for the understanding and the quantitative in-line monitoring of the homogenization process of a pharmaceutical suspension. Analyst, 131, 1137-1144 (2006). 

E. Widjaja, Y.Y. Tan and M. Garland, Application of band-target entropy minimization to on-line Raman monitoring of an organic synthesis. An example of new technology for process analytical technology, Org. Process Res. Dev., 11, 98-103 (2007). 

T.R.M. De Beer, M. AUeso, F. Goethals, et al.. Implementation of a process analytical technology system in a freeze-drying process using Raman spectroscopy for in-line process monitoring. Anal. Chem., 79, 7992-8003 (2007). 

The first demonstration of solid state fluorescence of API dates back to 1961, while its in-line use for final drug product manufacturing was not demonstrated until recently." While in its infancy as a process analytical technology for real-time monitoring and product parametric real-time release, the applications identified and in some instances demonstrated include (i) blend endpoint API content nniformity detection " (ii) segregation monitoring or API content at various process critical control points and (iii) at-line tablet content uniformity determination. The fundamentals of solid-state luminescence spectroscopy for pharmaceutical solids has been covered by Brittain."... 

R. P. Cogdill, C.A. Anderson and J.K. Drennen III., Process analytical technology case study. Part III calibration monitoring and transfer, AAPS PharmSciTech., 6(2) E284—E297 (2005). 

In summary, it appears that roller compaction pre- and postblends can be NIR monitored during scale-up, independent of batch size and blender type. Using real time NIR monitoring would advance blender unit operations knowledge and provide continuous information and assurance about specific unit operations such as roller compaction, a key FDA Process Analytical Technology goal. 

In a number of process analytical technology (PAT) applications in the pharmaceutical industry it is desirable to monitor rapidly and non-invasively the bulk content of drugs with high chemical specificity. Although NIR absorption spectroscopy has been used widely in this area its comparatively low chemical specificity places limits on its usefulness. As noted earlier, transmission Raman is particularly well suited for this application since it removes the key obstacle of conventional Raman, the subsampling problem [43]. Matousek and... 

Process Analytical Technology (PAT) has been shown to be able to monitor and control a high-shear granulation process and predict behavior upon scale-up. Through the exploitation of PAT, online control of the process may be achieved, which can mitigate... 

NIR monitoring of the granulation process was attempted by researchers at many major pharmaceutical corporations with a modest success. In particular, yet unpublished work by David Rudd of GlaxoSmithKline in England should be mentioned as a part of the global effort in the field of Process Analytical Technology. 

Keywords monitoring, quality control, process analytical technology, modelling... 

Validation and process analytical technology (PAT) require that we find and control the primary sources of product and process variation. Not many people realize that the current good manufacturing practice contain the words validation and variability in the same sentence. Such control procedures shall be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product (1). 

FIGURE 23.1 (See color insert following page 40). Process steps in a conventional drier monitoring operation versus a process analytical technology (PAT) drier application. 

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