On-line PAT Applications of Spectroscopy in the Pharmaceutical Industry

Of partieular interest is the PAT guidance, finalized in September 2004. Unlike the ehemical, petroleum, polymer and food industries, the pharmaceutical industry is under heavy regulatory serutiny. This is not just regulation by the FDA, but regulatory agencies worldwide. The delivery of safe and effeetive drug product to improve the quality of life neeessitates regulation. 

Many in the pharmaeeutieal industry will recall the Wall Street Journal artiele that deelared the manufacture of potato ehips more teehnologieally advanced than the manufacture of pharmaeeutieals. This may seem a harsh criticism, but it is honest. Dissolution has been used to test drug product quality since the 

Process Analytical Technology 2e Edited by Kadierine Bakeev 2010 John Wiley Sons, Ltd. 

With that said process analytical chemistry (PAC) has been commonplace in several industries, even the pharmaceutical industry, prior to 2004. Riebe and Eustace differentiate PAC from analytical chemistry with one word location. PAC is typically spectroscopy, separations or chemometrics, as apphed either at-, in- or on-line to manufacturing. Several comprehensive application reviews of process analytical chemistry have been published in Analytical Chemistry since 1987. In one of these reviews Workman et al. comment that PAT has continued to evolve as a more appropriate term than PAC while noting PAC has existed since 1911 but is just now finding common usage. The scope of PAT is much broader than that of PAC as the FDA guidance outlines the following desired state for manufacturing  

So PAC has indeed evolved to PAT, which encompasses not only process measurement, real-time quality assurance and control but process understanding to enable product quality by process design. The tools available to us for quality by design as defined by the FDA include  

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One indication of the developing interest in PATs in the pharmaceutical area is the number of book chapters and review articles in this field that have appeared in the last few years. Several chapters in The Handbook of Vibrational Spectroscopy3 are related to the use of various optical spectroscopies in pharmaceutical development and manufacturing. Warman and Hammond also cover spectroscopic techniques extensively in their chapter titled Process Analysis in the Pharmaceutical Industry in the text Pharmaceutical Analysis.4 Pharmaceutical applications are included in an exhaustive review of near-infrared (NIR) and mid-infrared (mid-IR) by Workman,5 as well as the periodic applications reviews of Process Analytical Chemistry and Pharmaceutical Science in the journal Analytical Chemistry. The Encyclopedia of Pharmaceutical Technology has several chapters on spectroscopic methods of analysis, with the chapters on Diffuse Reflectance and Near-Infrared Spectrometry particularly highlighting on-line applications. There are an ever-expanding number of recent reviews on pharmaceutical applications, and a few examples are cited for Raman,7 8 NIR,9-11 and mid-IR.12... 

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