Critical Quality Attributes Assessment and Testing Strategy for Biotherapeutics Development

摘要

Criticality assessment of product quality attributes forms the foundation of the Quality by Design (QbD) approach to drug development. This systematic approach to product development emphasizes product knowledge and process understanding along with process control based on sound science and quality risk management. Due to complexity of the molecular structure as well as the manufacturing process, development of biotherapeutics remains challenging. It is often difficult to fully evaluate the impact of the large number of quality attributes as related to safety and efficacy. The effects of manufacturing process parameters and material attributes on product quality variations are also difficult to fully characterize. For robust manufacturing operations, it is important that an integrated control strategy is developed and improved over time based on systematic process characterization along with implementation of appropriate risk assessment and mitigation throughout the product lifecycle. This article discusses the key concepts of critical quality attributes (CQAs) risk ranking based on prior knowledge and gathering of structure-function relationship information, consideration of process and stability impact on CQAs, and evolving the analytical testing panel as part of the integrated control strategy.