Abstract

Process Analytical Technologies (PAT) are used to provide timely analysis of critical quality parameters with the end goal of improving final product quality as well as reducing manufacturing costs, thereby significantly benefiting the Pharmaceutical Industry. PAT involves mostly on-line or in-line testing, which can be an invasive or non-invasive process that analyzes the sample while it is part of the process stream. There is no sample preparation in the testing, thus saving time and avoiding possible errors in sample preparations. PAT uses vendor specifications based on science and common sense to exhibit, ‘fit for purpose ’ rather than conventional USP paradigm, ‘one specification fits all,’ which is based upon documentation but lacking in scientific logic. The current FDA guidance is to adapt its traditional regulatory scrutiny to PAT advancement. The Pharmaceutical Industry is using innovative PAT methods to improve the logical basis for establishing regulatory specifications, promoting continuous improvement and improving manufacturing. Multivariate tools are used in PAT for design, data acquisition and analysis. These tools are used in conjunction with statistical design of experiments, response surface methodologies, and process simulation and pattern recognition under the control of various knowledge management systems. For example, NIR Spectroscopy is used in drug product production at almost each step of tablet manufacturing from raw materials control to content uniformity analysis of the dosage unit. The spectral data set is usually multivariate in nature. This is due not only to the different ranges and peaks in a spectrum, which are influenced by the nature of the product but also due to several interlinked factors that influence the appearance of the spectrum. When NIR is used in PAT, the materials are blended to uniformity rather than a fixed time. This type of advance control gives better batch-to-batch consistency and better product quality, which eliminate reworks/rejects, and there are no Out Of Specification (OOS) reports to file under PAT. The product is “engineered for Quality”, as opposed to “tested to Quality”.

Keywords: Process, Analytical, Technology, Analyzer, NIR