The early 21st century medical authority from SUA (Food and Drug Administration – FDA) and Europe (European Medicines Agency – EMA) reached the conclusion that science is used only in drug discovery while medicine manufacturing is performed mostly empirically, which may have consequence on the quality of the drug delivered to the patients [i].
So, they started a series of initiatives for changing the drug authorization process, that forced the drug producer to adopt state-of-the-art technological advances and science in drug development, production and quality assurance. The most important initiatives are those related to Process Analytical Technology (PAT) and Quality by Design (QbD) concepts in regulatory processes.
FDA and EMA describe PAT as ”a system for designing and controlling manufacturing through timely measurements (i.e. during processing) of critical quality and performance attributes for raw and in-process materials and also processes with the goal of ensuring final product quality” [ii, iii,iv]. QbD is described by FDA and EMA as “systematic approach to development that begins with predefined objectives and emphasises process and product understanding and process control, based on sound science and quality risk management” [ii]. QbD may include, for example, incorporation of prior knowledge, results of experimental studies using design of experiments or multivariate data analysis, establishment of a control strategy, use of quality risk management and use of knowledge management throughout the lifecycle of the product [v].
Sustained release drug delivery systems are developed to modulate the drug in order to achieve specific clinical objectives that cannot be attained with conventional dosage forms [vi,vii]. Hydrophilic matrices represent one of the systems most widely used for controlling drug release, but the mechanisms involved in drug release from these matrix systems are complex and depend on many factors [viii,ix]. Currently, many of those factors are not investigated/monitored during the manufacturing process and a higher or lower variability of these factors affects product variability (in this case drug release profile variability/bioavailability)[x,xi].
Actually, the difficulty in drug development is to deeply understand the formulation and technological process and to find functional relationships that link formulation attributes/process parameters to critical quality attributes (CQAs) or critical process parameters (CPPs) [xii]. A scientific approach to overcome this difficulty is applying QbD concept in each step of the technological process. Other difficult problem today in drug manufacturing is monitoring the value of CQAs/CPPs once identified. A lot of parameters, such as drug particle size, drug polymorphism, polymer characteristics (particle size, intrinsic viscosity), percentage of drug/polymer/filler excipients in powder/granules blend for compression, tablet porosity, tablet hardness can be determined by NIR-spectroscopy, but this technique needs specific approaches in method development and validation [xiv,xiii,xiv,xv,xvi].
References:
QbD-PAT MatrixRS 