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Achieving 6 Sigma Quality in Medical Device Manufacturing by Use of DoE and SPC
Achieving 6 Sigma Quality in Medical Device Manufacturing by Use of DoE and SPC
PHARMACEUTICAL ENGINEERING
This article
highlights how a
manufacturer of
medical devices
obtained Six
Sigma quality in
production by
the use of
Design of
Experiments
(DoE) and
Statistical
Process Control
(SPC) and
discusses how
these tools can
be an important
step toward the
Future Desired
State.
Introduction
Background
The FDA defines in their Guidance for Industry1 Process Analytical Technology (PAT) as:
The Agency considers PAT to be a system for
designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final
Training Subjects
Training Duration
Roles
100
1 day
10
2 weeks
Green Belts.
Project participant in DoE and
SPC projects with supervision
4 weeks + project
Black Belts.
Project Manager.
Supervisor.
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Yield %
Cp before Sorting
System
Downtime each
year (days)
CoPQ % of
Sales (8)
CoPQ % of
Sales (9)
30
0.33
255
>40
>70
Non competitive
69
0.67
112
30-40
>40
Non competitive
93
1.00
24
20-30
25-40
Average Pharma
Sigma = 5 after sorting (3)
99.4
1.33
2,27
15-20
15-25
99.98
1.67
0.085
10-15
5-15
100
2.00
0.0012
<10
<1
100
2.33
0.000069
100
2.67
Table B. Relation between Sigma Level and Cost of Poor Quality. Sigma Level is the number of standard deviations between target value
and specification limits.
Lean
Numberof Steps
Cp=1,00
3 sigma
Cp=1,33
4 sigma
Cp=1,67
5 sigma
66807
6210
233
129151
12381
465
187330
18514
698
10
241622
24608
930
14
292287
30665
1163
17
339568
383689
424863
463287
10
499143
20
749142
117133
4642
68
50
968481
267617
11565
170
100
999007
463615
22997
340
1000
1000000
998029
207574
3392
a 1395
m
g
i 1627
S
48611ix
1860
S
2092
n54519
a
e
L 60390
2324
Cp=2,00
6 sigma
36684
20
42666
24
27
31
34
Table C. Relation between ppm error rates, number of process steps, and Cp for each step.
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Six Sigma
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Train Staff
is done with fixed energy, i.e., the welder uses the time needed
to deliver the set point energy.
Establish Relationships
Based on the conclusions from the screening experiment, the
most important control variables were investigated in more
detail in a Response Surface Experiment. This was done after
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Figure 5. Relation between external CTQs (separation force left, flush right) and internal CTQ (height difference).
right blue curve is flush grade 3 (high flush) area. Since the
curves are almost vertical, height difference is a good indicator for flush.
Optimize
From the results of the Response Surface Experiment, the
optimal setting of the control variables for obtaining the
optimal internal CTQs were found. The optimization was
easy to implement since it was only a matter of changing set
points for the control variables. With the optimized settings,
Ppk increased from 0.7 to 2.0.
Control Strategy
To keep the optimized conditions for the external CTQs
(welding strength and no flush) over time it was decided to
make statistical control charts on the internal CTQs (height
difference and welding time).
The plot of mean values of height differences versus time
is seen in the upper chart on Figure 6. It is easy to read for the
operator, who shall monitor if new mean values are in the red
zone. If this is the case, actions are needed. Also, the capability and performance index are shown in the table in the upper
right corner. Since this process is on target, in statistical
control, and follows a normal distribution, there is not much
difference between Cp, Cpk, Pp, and Ppk. They are all above 2
equal to Six Sigma quality. Besides being shown on-line at
welding time. So the first thing the operator does if there are
OOC on height differences is to see if there are also OOC on
welding time. If this is not the case, the first action will be to
clean the height measurement systems because the process
indicator (welding time) shows no abnormal behavior. If the
cleaning does not help or if both height difference and time
are OOC, welding parameters are adjusted or maintenance is
performed. The decision to adjust parameters or to do maintenance is dependent on the position within Design Space.
As can be seen in Figure 4, there are several options for
choosing parameters to adjust height differences. Ideally, one
should choose only one and fix the others to make it operational on the shopfloor. When choosing the parameter, it can
be beneficial to look at how process parameters influence the
CTQ relations shown in Figure 5. In Figure 8, it is seen that
the lower the pressure, the better the height difference works
as a barrier for low forces due to a lower slope on the
correlation curve. Therefore, it is not a good solution to use
pressure to adjust height difference because it is best to have
it at a low value at all times. For this, process energy was
chosen to adjust height difference keeping other parameters
fixed.
Validate
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Conclusion
References
1. http://www.fda.gov/cder/guidance/6419fnl.htm.
2. Abboud, Leila and Scott Hensley, New Prescription for
Drug Makers: Update the Plants, The Wall Street Journal, 3 September 2003.
3. http://www-1.ibm.com/services/us/imc/pdf/ge510-4034metamorphosis-of-manufacturing.pdf.
4. ISO21247 (2005).
5. Watts, D.C., and J.E. Clark, The Journal of PAT, Vol. 3,
Issue 6, December 2006, pp. 6-8.
6. Department of Defense Test Method Standard, DoD Preferred Methods for Acceptance of Product, Mil-Std-1916,
April 1996.
7. ISO21747 (2006).
8. Harry, M.J., Quality Progress, May 1998, pp. 60-64.
9. Clark, T.J., Success Through Quality, Quality Press 1999,
ISBN 0-87389-441-3, www.successthroughquality. com.
10. DeFeo, Joseph A., Quality Progress, Vol. 34, No. 5, May
2001, pp. 29-37.
11. Brindle, A., and Per Vase, Process Review for PAT
Selecting Cost Efficient PAT Projects, Pharmaceutical
Engineering, November/December 2006, Vol. 26, No. 6,
pp. 70-78.
12. ICH, Q8 Pharmaceutical Development, Glossary, May
2006.
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