ABSTRACT
Chromatographic analyzers are the most widely employed instrumentation in the area of process analysis [1]. This usage is also the case in the pharmaceutical industry, where liquid chromatography is most often the technique of choice for the analysis of substances associated with the manufacture of drug substances and drug products [2]. Historically, pharmaceutical manufacturing has generally consisted of batch processes where analytical tools, including chromatography methods, were used to test a sample of the end product to verify and ensure its quality. The level of quality in a process can also be achieved using on-line process monitoring and control techniques that can improve the efficiency and quality of the product. However, these techniques have not been widely used in the pharmaceutical industry due to the regulatory uncertainty “which may result from the perception that our existing regulatory system is rigid and unfavorable to the introduction of new technologies.” [3]
To facilitate the introduction of new and efficient technologies, the Food and Drug Administration (FDA) launched in 2001 the Process Analytical Technology (PAT) initiative. The FDA’s current thinking on PAT was published in a draft guidance PAT — A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance [3]. According to this guidance, PAT is considered to be 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 and processes with the goal of ensuring final product quality.” [3] Although the use of process analytical tools is not a new approach, many of the techniques have been used only on a limited basis by a very small percentage of the pharmaceutical industry [4].
