Chemometrics-Based Process Analytical Technology (PAT) Tools: Applications and Adaptation in Pharmaceutical and Biopharmaceutical Industries

Abstract

Process analytical technology (PAT) is used to monitor and control critical process parameters in raw materials and in-process products to maintain the critical quality attributes and build quality into the product. Process analytical technology can be successfully implemented in pharmaceutical and biopharmaceutical industries not only to impart quality into the products but also to prevent out-of-specifications and improve the productivity. PAT implementation eliminates the drawbacks of traditional methods which involves excessive sampling and facilitates rapid testing through direct sampling without any destruction of sample. However, to successfully adapt PAT tools into pharmaceutical and biopharmaceutical environment, thorough understanding of the process is needed along with mathematical and statistical tools to analyze large multidimensional spectral data generated by PAT tools. Chemometrics is a chemical discipline which incorporates both statistical and mathematical methods to obtain and analyze relevant information from PAT spectral tools. Applications of commonly used PAT tools in combination with appropriate chemometric method along with their advantages and working principle are discussed. Finally, systematic application of PAT tools in biopharmaceutical environment to control critical process parameters for achieving product quality is diagrammatically represented.

Role of Knowledge Management in Development and Lifecycle Management of Biopharmaceuticals

“…2, some of the reviewed technological solutions are found to be concentrated on using specific sources of knowledge. For instance, there is a predominance of statistical analysis tools that use knowledge from manufacturing experience, such as multivariate data analysis of spectroscopic datasets (22,49), chemometric tools for implementation of process analytical technologies (PAT) (23), and Intelligent Agents that supervise biotechnological processes (50)). Aside from their major role in manufacturing, these statistical analysis tools are also used for the management of development information (51).…”

“…While advantageous in cases where mechanistic process knowledge is scarce; the need for extensive training datasets is often a limiting factor for the applicability of such models during initial process development stages. While useful for data mining, hypothesis generation, and analysis of multivariate datasets generated by PAT instrumentations (22,85), the parameters of statistical models are more difficult to interpret; therefore, are not as useful as mechanistic models to serve as a store of available process knowledge.…”

“…They create a common, explicit, and platform-independent vocabulary that is both machine accessible and human usable.Holistic ontologies in pharmaceutical engineering (18), ontologies for pharmaceutical mathematical knowledge modeling (19)Analysis Visualization Information arrangement that displays a set of data easily understood by a wide audience. Graphs, charts and Response Surface Methods are included.Visualizing metabolic networks (20), Response Surface Methodology in biotechnology (21) Statistical analyzers Provide quantitative measure of the inherent variability of a phenomena, assessing the current state of control and enabling process improvement.Chemometrics-based PAT (22), Integrated statistical platforms to laboratory management (23) Intelligent agents Decision support tools that are grounded in the emulation of skills for reasoning and inference. Their system is composed by a knowledge base, an inference engine and an interface for the user.Intelligent process management in continuous pharmaceutical operations (24), intelligent decision support in pharmaceutical development (25) Models and simulation Effective integration of knowledge, information, and assumptions with experimental data in one unified representation, to predict outcomes and express relationships.Modeling in decision making for drug development (26), multiscale pharmaceutical mechanistic modeling (27)Dissemination Network and web technologies Interfaces and platforms that help to interconnect resources inside the boundaries of an organization, exploiting the knowledge within the firm.…”

Development and validation of an at-line fast and non-destructive Raman spectroscopic method for the quantification of multiple components in liquid detergent compositions

“…Thus, advanced manufacturing practices are being implemented in the pharmaceutical, chemical, biotechnological and food industry, enhancing process efficiency and guaranteeing product quality [3][4][5][6][7][8][9]. The consumer goods industry, on the contrary, has been slow at adapting this PAT approach.…”

Application of Support Vector Regression for Simultaneous Modelling of near Infrared Spectra from Multiple Process Steps

“…Partial least-squares regression (PLS) is the most widely applied method for regression tasks. [1][2][3] It assumes an approximate linear relationship between the quality parameter and the intensity of its absorption bands, and is thus feasible for spectral data that follow Beer's law. Moreover, PLS is particularly suited when data are high dimensional and multicollinear, which is often the case with spectral data.…”