PAT and QbD tools. MIR and NIR spectroscopy applications

MAGGIO, RUBÉN M.

Virtual

Congreso; VI Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2020+1); 2021

RICIFA

The application of the principles of the Quality by Design (QbD) approach in the pharmaceutical industry was introduced by Juran in the ´90s; however, QbD becomes popular after the publication of the ICH Guidelines Q8, Q9 and Q10. These guidelines provide a structure to define the critical quality attributes (CQA), design space (DS), the manufacturing process and the control process of pharmaceutical products. Process Analytical Technologies (PATs) can be defined as a system for the design, analysis and control of the pharmaceutical production procedure through measurements of critical process parameters (CPPs). They can be understood as measurements made on raw materials, intermediate material or process parameters during the operation of the process to improve the quality of the final product. The PATs promote the adoption of new analytical techniques by the pharmaceutical industry (technological innovation), which are designed to improve knowledge and control of manufacturing processes.PATs implementation is based on the use of Design of Experiments (DOE) tools to define a DS by analyzing the CPPs. Once the sources of variability of a process are identified, PAT tools can be used to control that the process is within the DS or it can be used for expansion of the DS. PAT tools are mostly spectroscopic instruments since they must be able to reflect the state of the process in real-time.Vibrational spectroscopies (NIR, MIR and RAMAN) are methodologies of choice for PATs because they are able to provide chemical and physical information in the same measure (spectrum). In addition, they present several advantages in their implementation due to are non-destructive and non-invasive techniques; measurements are fast and have a low cost of analysis, once implemented. Additionally, such spectroscopies may not require sample preparation or chemical reagents, are easy automatable and allow the determination of several components at the same time with a single measurement. Moreover, vibrational spectroscopy is easily applicable in the process or in the laboratory (on-line, in-line or at-line); the possibility of using probes with optical fibers (remote measurements) and the ability to penetrate various types of containers (glass, plastic) allowing determinations in process or final product (also packaged ones).However, high initial investment and the need for trained personnel are two of the main barriers that delay its implementation. From the technical point of view, the feasibility to carry out measurements (using probes, cells and windows), to reach the required sensitivity and the development of multivariate calibration are the most important factors for the implementation of PATs. The development of multivariate models requires large sets of samples in order to incorporate various sources of variability; continuous maintenance of the model and in many cases a reference analytical method. However, the development of multivariate model is usually a starting point for the implementation of PAT tools in the pharmaceutical industry.