FMEA-辉瑞企业培训资料

INTO A PRODUCT; IT HAS TO BE
BY DESIGN
“Market Standards”
Science of Design + Manufacturing Science = Quality by Design
RISK/BENEFIT AND QUALITY
Label
Harm
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
MANAGEMENT GOALS
Improving quality and ensuring availability Optimal use of our resources
A systems approach to CMC review and CGMP investigations
tity
Complexity A range of uncertainty with respect to identity of “active moiety”, purity and stability of materials used in evaluation of pharmacological and toxicological attributes (if a mixture; variability adds additional uncertainty) Variability in the extent and rate of delivery of “active moiety” to the sites of action and variability in the pharmacological & toxicological response and measurement systems further adds uncertainty
Good pharmaceutical quality represents an acceptably low risk of failing to achieve the desired clinical
/toc.asp
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.
Woodcock, 2004
A SYSTEMS APPROACH
Science of Design
Manufacturing Science
Deliver Quality by Design
State of Control & Continuous Improvement
QUALITY CAN NOT BE TESTED
Based on knowledge and process understanding
Achieving “quality by design” Demonstrating “science of design” Continuous learning and improvement through
MANAGING PHARMACEUTICAL QUALITY: RISK OR UNCERTAINTY MANAGEMENT?
Ajaz S. Hussain, Ph.D.
Office of Pharmaceutical Science CDER, FDA
PQRI Workshop February 1, 2005
Characteristics important to desired performance must be derived from a combination of prior knowledge and experimental assessment during product development.
Acceptable Risk/Benefit
Quality
No benefit (placebo effect)
MANAGING PHARMACEUTICAL QUALITY
Quality of a new molecular entity (a potential drug)
Intrinsic pharmacological & toxicological attributes
WHAT IS QUALITY?
attributes. 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.
“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