The product parameters that must be evaluated for drug substance and drug product in a cGMP setting are defined in ICH Q6B (Specifications: test procedures and acceptance criteria for biotechnological/biological products). The parameters specified in ICH Q6B are:
Physicochemical properties
Biological activity
Immunochemical properties
Purity (impurities and contaminants)
Quantity
At Labcorp, we have deep experience in development, validation and cGMP use of methods that cover all the parameters requested in ICH Q6B. From a physical chemistry perspective, this includes mass spectrometry and classical methods such as electrophoresis and chromatography. Biological and immunological properties are measured using cell-based assays, ELISAs and surface plasmon resonance analysis. Typical release and stability testing also requires compendial assays, which, while not requiring development, do need to be verified before cGMP use.
In keeping with the recent developments in regulatory guidelines, Labcorp’s biopharmaceutical CMC services operate to ICH Q14 (Analytical Procedure Development) and ICH Q2(R2) (Validation of Analytical Procedures) for analytical procedure development and validation.
ICH Q14 is a recent guideline that describes analytical procedure development. Previously, no guidance specifically covered this topic, resulting in a lack of clarity on what to present to regulators. Traditionally, analytical development has largely been an ad hoc process. However, the introduction of ICH Q14 aims to formalize and align the scientific approach to analytical development throughout the analytical life cycle.
The recent revision of ICH Q2 is designed to complement ICH Q14, emphasizing the importance of validation parameters during analytical procedure development and early robustness evaluation along with a risk-based approach to validation and life cycle management.
The approach outlined in ICH Q14 is centered on the quality by design (QbD) concept, defined as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.” It was originally introduced for use with pharmaceutical process development and defined in ICH Q8(R2) (Pharmaceutical Development) and ICH Q9 (Risk Management).
The primary components of an analytical quality by design (AQbD) approach to assay development are the production of an analytical target profile (ATP), method selection, risk assessment, method development, design and implementation of a control strategy, and monitoring of the method performance.
At Labcorp, we have integrated ICH Q14 into our assay development process. We recommend following the AQbD approach as it leads to better understood and more robust methods (with greater regulatory flexibility), as well as fewer issues later, saving time, effort and cost over the whole method life cycle.
