Process Capability Session (CpK/PpK)

Process Capability Session
(CpK/PpK)
IFPAC Conference – Washington DC
January 23, 2014
Brian Eden / Kenneth Coté
Process Capability Applications
•
What we’re hearing in the Industry
•
APR/ PQR
•
Metric Selection
•
Analytical Process
•
Capability Examples
•
Proceduralization
What we’re hearing in the industry
•
Top 10 metrics - FDA
•
ICH references
•
Recent World Health Organization observations
related to CpK
APR / PQR
•
Current State
– APR / PQR documents are prepared in accordance with cGMP
– However…..Presentation of data tends to be tabular without statistical analysis.
•
Future State
– Standardizing across sites and affiliates
– Use of Control Charts, CpK calculation and graphs
– More detailed understanding of Product trends
• Proactive vs. Reactive
Metric Selection
Parameter Diagram
• Specified Formulation
• Equipment choices
• Analytical methods
Controllable
Factors (XC)
• Handing techniques
• Sterility
• Blend Uniformity
• API
Inputs
• Excipient
• Labor
• Energy
• Content Uniformity
Production
Outputs (Y’s)
• Stability
• Residual Solvents
Process
• Assay
• Dissolution
• Related Substances
To what metrics do
we apply this?
• Foreign Material
• Ambient temp. and humidity
• RM particle size, polymorphism
• Random human errors
• Normal variation in Xc factors
Noise Factors (XN)
Analytical Process
Source
Raw data
•
•
•
Analytical Software
Outsourced
Laboratories
Manual Collection
Refine
Data
•
•
•
•
Filter / sort data in MSExcel®
Gaps in data?
Incorrect formats
Pooling considerations
Statistical
Analysis
•
•
•
•
Copy to Minitab ®
Verify Assumptions
Control Charts
Capability Analysis
Prepare
Report
•
•
•
Report in MS-PowerPoint®
Analysis
Business Decision
Oral Solid Dose Content Uniformity Example
Process Capability of CU Acceptance Value
Xbar-S Chart of CU Acceptance Value by Year
2010
Johnson Transformation with SU Distribution Type
-3.357 + 1.465 * Asinh( ( X - 0.853 ) / 0.348 )
2011
Sample Mean
750.0%
UCL=424.0%
_
_
X=290.2%
250.0%
LCL=156.4%
0.0%
Month
Year
400.0%
Sample StDev
LB*
500.0%
9
2010
12
2010
2010
1
2011
2
2011
3
2011
5
2011
6
2011
7
2011
8
2011
U S L*
transformed data
P rocess Data
LB
0
Target
*
USL
15
S ample M ean
2.90185
S ample N
54
S tDev (O v erall) 1.64437
O v erall C apability
Pp
*
PPL
*
P P U 1.01
P pk 1.01
C pm
*
A fter Transformation
LB*
Target*
U S L*
S ample M ean*
S tDev (O v erall)*
2011
300.0%
-5.74322
*
3.08505
-0.0986806
1.05564
UCL=248.7%
200.0%
_
S=151.1%
100.0%
-4.5
LCL=53.4%
0.0%
Month
Year
9
2010
12
2010
1
2011
2
2011
3
2011
5
2011
6
2011
7
2011
8
2011
Tests performed with unequal sample sizes
Control charts – 2 Stages by year
O bserv ed P erformance
P P M < LB 0.00
P P M > U S L 0.00
P P M Total 0.00
-3.0
-1.5
0.0
1.5
E xp. O v erall P erformance
P P M < LB*
*
P P M > U S L* 1280.93
P P M Total
1280.93
Capability Analysis
3.0
Injectable Assay Example
Process Capability of Average Composite Assay
LSL
USL
Within
Overall
P rocess Data
LS L
95
Target
*
USL
105
S ample M ean
100.677
S ample N
35
S tDev (Within)
0.800373
S tDev (O v erall) 0.758902
P otential (Within) C apability
Cp
2.08
C P L 2.36
C P U 1.80
C pk
1.80
O v erall C apability
Pp
PPL
PPU
P pk
C pm
96.0
O bserv ed P erformance
P P M < LS L 0.00
P P M > U S L 0.00
P P M Total
0.00
Control charts – All Stages
97.5
E xp. Within P erformance
P P M < LS L 0.00
P P M > U S L 0.03
P P M Total
0.03
99.0 100.5 102.0 103.5 105.0
E xp. O v erall P erformance
P P M < LS L 0.00
P P M > U S L 0.01
P P M Total
0.01
Capability Analysis – Stage 3
2.20
2.49
1.90
1.90
*
Sustainability
•
Documentation
– Global directives
– APR / PQR templates and Standard Operating Procedures
•
Education
– Workshops – Intro to Stats and Minitab ®
– Workshops- APR / PQR stability
– Lean / Sig Sigma Green Belt/Black Belt training
– Minitab ® software Enterprise License

Download Report