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Quality
Lawrence X. Yu, Ph.D.
Deputy Director
Office of Pharmaceutical Quality
Center for Drug Evaluation and Research
Food and Drug Administration
Labeled Use
Safety and Efficacy
DEFINE Quality
Target Product Profile
Overview of QbD
Product Design and
Understanding
TARGET
Control
Strategy
Continual
Improvement
DESIGN and
UNDERSTANDING
IMPLEMENTATION
5
Quality by Design
Specification acceptance criteria are based on
performance
Testing may not be necessary to release batches
L. X. Yu. Pharm. Res. 25:781-791 (2008)
6
USL LSL
6 ST
USL Mean
3 ST
Cpkl
Mean LSL
3 ST
10
Bilateral
specification*
Capability
Rating
0.333
68.27
158650
317300
Terrible
0.667
95.45
22750
45500
Poor
1.0
99.73
1350
2700
1.333
99.9936
32
64
Capable
1.667
99.99994
0.3
0.6
Good
2.0
99.9999998
0.001
0.002
Excellent
Marginally
capable
* Process mean is centered at middle of the specification limits and has normal distribution
11
Mean LSL
Ppkl=
3SD
12
13
14
Control Chart
6.0
USL
UCL
Quality 5.0
attribute
(unit)
CL
LCL
LSL
4.0
30
40
Sample #
50
60
A set of data
A central line (CL) (mean)
Two statistical process control limits (UCL and LCL) (Is the process
Stable?)
15
Sources of Variation
Variation can be categorized as
either:
Common causes of variation
Inherent to a system, random, always present and
hence predictable within statistical limits
Eliminate inherent variability (noise) is difficult
17
18
Observations to
inform premarket
review decisions
Surveillance
Inspection Subgroup
Draft Protocol
Draft Protocol
Pre-Approval
Inspection Subgroup
Observations on state
of quality in a facility
to assess quality risk
19
Quality System
Management Responsibilities
Quality Unit Responsibilities
Training and Personnel Development
Process Performance and Product Quality
Monitoring System (PPPQMS) &
Preventative Action
Investigations and Corrective Action
Change Management System
Data Integrity All Systems Oversight
Continuous improvement
20
Quality Metrics
Vision
A more rigorous and comprehensive approach to quality
surveillance that allows for improved monitoring of
current status across the inventory of FDA-regulated
drug products and manufacturing sites
22
Process Capability/Performance
Process capability is a leading, useful indicator. However, its
calculation is relative complex
23
Amgen
24
Business Case
25
26
27
28
Summary
Process capability is a leading, useful indicator
although its calculation is relative complex
Quality standard should be clinically relevant and a
surrogate of clinical performance
29