New trends in Quality Control: new compendial and ICH guidelines outlining Quality by Design (QbD) principles

Quality Control (QC) is critical in the pharmaceutical industry and involves the set-up and use of reliable and robust analytical procedures (AP). The AP lifecycle includes procedure development, validation, transfer, verification, ongoing AP performance monitoring and AP maintenance. International Conference on Harmonisation (ICH) draft guidelines Q14 and ICH Q2(R2) describe the development and validation activities, respectively, that should be carried out during the AP lifecycle used to assess the quality of drug substances and drug products. ICH Q14 outlines the scientific principles for developing, managing, and submitting APs, while ICH Q2(R2) provides guidance on how to ensure that an AP is appropriate for its intended purpose through validation activities (drug quality assurance). USP Chapter <1220> provides a framework that incorporates a holistic view of various aspects of the AP lifecycle to ensure the reliability and accuracy of APs used in pharmaceutical analysis, being driven by Analytical Quality by Design (AQbD) principles. Although it is not mandatory to adopt AQbD when developing a new AP, the issue of ICH draft guidelines Q14 and Q2(R2) is expected to facilitate the shift from the traditional univariate AP development to the new quality paradigm based on QbD riskbased approach. The possibility to define the Method Operable Design Region (MODR) and to establish analytical control strategies for the procedure can help the industry to ensure fitness for use during the AP lifecycle. MODR may be designed by using systematic approaches for knowledge acquisition and management (e.g., Design of Experiments - DoE) and it is defined as “a combination of analytical procedure parameter ranges within which the analytical procedure performance criteria are fulfilled and the quality of the measured result is assured”. Moving within the qualified MODR may not require regulatory notification, and validation may be performed at the edges of the MODR in order to assure transferability of the procedure. AP lifecycle also consists of the Analytical Target Profile (ATP) and the use of quality risk assessment tools (e.g., DoE). The main benefits of AQbD implementation include the acquisition of an in-depth AP knowledge and the design of a more robust procedure. In this context, pharmacopeias and regulatory bodies have been encouraging the pharma and biopharma industry to implement AQbD principles to promote continuous quality improvement and help advance quality of medicines.