FMEA辉瑞企业培训资料.pptx

Managing Pharmaceutical Quality: Risk or Uncertainty Management?
Ajaz S. Hussain, .
Office of Pharmaceutical Sciencet Standards”
Science of Design + Manufacturing Science = Quality by Design
Risk/Benefit and Quality
Harm
Acceptable
Risk/Benefit
Quality
Label
No benefit (placebo effect)
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 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
Managing Pharmaceutical Quality
Quality of a drug product
For establishing proposed therapeutic claim (label)
Drug product manufactured for clinical trials
After successful demonstration of therapeutic claim (acceptable risk-to-benefit ratio)
Drug product manufactured for commercial distribution
Life cycle of the product (shelf-life, exclusivity period, generic competition, post-approval changes,…)
Drug product manufactured at many different facilities, changes in the process, different manufactures,…
Uncertainty, Variability and Risk
Quality – Clinical Connection
How does a product formulation and its manufacturing process impact clinical performance?
Without a clear understanding we are uncertain (lack of knowledge)
In decision making there are many advantages in distinguishing between uncertainty, variability (random variation) and risk
Goals and Characteristics of a Quality Decision System: Example
Goal: expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling
Characteristics
Uncertai