Quality-by-design of nanopharmaceuticals - a state of the art.

Pharmaceutical Quality-by-Design is a risk-based approach of drug development relying on the understanding of both the product and the process. This state of the art analyzes 24 studies published during the last ten years. A risk modeling of the nanomaterial formulation and manufacturing is firstly presented. After a brief history of the QbD approach, its basic components are recalled in a second part. The most critical material attributes, process parameters, quality variables and measurement technologies are reviewed. Specific deficiencies are also emphasized such as the absence of prior risk assessment, production scale-up, process analytical technology and control strategy. Finally, perspectives and development priorities are drawn to improve the implementation of this integrative approach of quality and safety in nanomedicine.