辉瑞Hussain.pptVIP

Managing Pharmaceutical Quality: Risk or Uncertainty Management? Ajaz S. Hussain, Ph.D. Office of Pharmaceutical Science CDER, FDA PQRI Workshop February 1, 2005 What is Quality? What is pharmaceutical quality? consistent delivery of the label performance and lack of contamination. operationalzed via a set of pre-specified quality attributes (e.g., specifications, limits) and through the CGMP regulations. FDA, in its quality definition, is standing in for the customer—and it is apparent that health care practitioners and patients highly value an additional drug attribute: product availability Good pharmaceutical quality represents an acceptably low risk of failing to achieve the desired clinical attributes. Management Goals Improving quality and ensuring availability Optimal use of our resources A systems approach to CMC review and CGMP investigations Based on knowledge and process understanding Achieving “quality by design” Demonstrating “science of design” Continuous learning and improvement through “manufacturing science” An Approach for Quality – Risk Connection Concept of Quality by Design (QbD) Product and process performance characteristics are scientifically designed to meet specific objectives, not merely empirically derived from performance of test batches Characteristics important to desired performance must be derived from a combination of prior knowledge and experimental assessment during product development. From this knowledge and data, a multivariate model linking product and process measurements and desired attributes may be constructed. Clinical study would then be viewed as confirmatory performance testing of the model. A Systems Approach Quality can not be tested into a product; it has to be by design Risk/Benefit and Quality Managing Pharmaceutical Quality Quality of a new molecular entity (a potential drug) Intrinsic pharmacological toxicological attributes Identity Complexity A range of uncertainty with respect to identity of “active m