Analytical Quality by Design Approach to Test Method Development and Validation in Drug Substance Manufacturing

Abstract

Pharmaceutical industry has been emerging rapidly for the last decade by focusing on product Quality, Safety, and Efficacy. Pharmaceutical firms increased the number of product development by using scientific tools such as QbD (Quality by Design) and PAT (Process Analytical Technology). ICH guidelines Q8 to Q11 have discussed QbD implementation in API synthetic process and formulation development. ICH Q11 guidelines clearly discussed QbD approach for API synthesis with examples. Generic companies are implementing QbD approach in formulation development and even it is mandatory for USFDA perspective. As of now there is no specific requirements for AQbD (Analytical Quality by Design) and PAT in analytical development from all regulatory agencies. In this review, authors have discussed the implementation of QbD and AQbD simultaneously for API synthetic process and analytical methods development. AQbD key tools are identification of ATP (Analytical Target Profile), CQA (Critical Quality Attributes) with risk assessment, Method Optimization and Development with DoE, MODR (method operable design region), Control Strategy, AQbD Method Validation, and Continuous Method Monitoring (CMM). Simultaneous implementation of QbD activities in synthetic and analytical development will provide the highest quality product by minimizing the risks and even it is very good input for PAT approach.

Statistical tools and approaches to validate analytical methods: methodology and practical examples★

“…The design and execution of the studies requires thorough knowledge of the product being tested as well as a good understanding of the analysis technique. New regulatory guidelines are being published [26][27][28][29][30] that govern the expectations of regulatory agencies throughout the world for methods development and validation. There is need to meet current regulatory standards.…”

Contribution to the Optimization of a Gas Chromatographic Method by QbD Approach used for Analysis of Essential Oils from Salvia officinalis

“…As per ICH Q8 guidance process robustness is defined as Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality [23]. Process understanding will provide the sufficient knowledge for establishing robustness parameters by evaluating different operating conditions, difference scales, and different equipments [25].…”

“…However, it is recommended to implement QbD approach in analytical method development termed as Analytical Quality by Design AQbD. These two scientific approaches (QbD and AQbD) can be progressed in equal time [25,26]. Based on the principles of sound science and quality risk management, the QbD approach enables enhanced understanding of the Critical Method Variables (CMVs) influencing the Critical Analytical Attributes (CAAs) and the method performance.…”

Stability‐indicating RP‐HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

“…It highlights product and process understanding and process control, based on sound science and quality risk management (ICH, 2009). Some reports detail the use of the QbD principle for the optimization of analytical methods (Orlandini, Pinzauti, & Furlanetto, 2013;Raman, Mallu, & Bapatu, 2015). The key function of the QbD concept is to build a visual "design space" in which the technique is robust.…”