01/20/2011 1
QbD Methodology Aids in Achieving Real Time Release of Medical Device Components
Lee Huston - Baxter
Presenter(s), Arial 18pt GrayTitle/Function/Business
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
01/20/2011 2
Topics
• Initial Process Selected for Real Time Release
• Selecting the Design Space using Scientific Method
• Developing Multivariate Model
• Implementing Model for Real Time Release
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
QbD & PAT in Practice
• Often monitoring & control strategies used to support QbD are derived without representative variation in the inputs
– Material Qualities (Viscosity changes)
– Environment (Material moisture content)
– Equipment (Type, condition, age, etc.)
• Including input variation in the design space allows for greater production flexibility
– Manage greater raw material variation
– Manage operator driven changes
– Reduced quality variations
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Motivation for Change
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1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Injection Molding DPM'sProcess Improvement Trends / Results
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Motivation for Change
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• Was tasked with continuing the trend shown above
– Improve versus maintain
– Automated versus Manual
– Science versus Black Art
• Discovered PAT and learned of what the FDA / Pharma industry was trying to accomplish
– Worked to become proficient in multivariate methods (PCA initially)
– Started following Pharma closely looking for parallels
– Attended this conference (IFPAC) regularly to understand the current state
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Medical Device Components
• Typically extremely low cost
• Very High Volume
– 650+ million components per year
– Cycle time of 8 – 45 sec
– Parts per cycle: 2 - 64
• Typical Sampling Plans do not provide adequate protection against defects
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Motivation for Real Time Release
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Medical Device Components
• Defect Rates are very low
• Process is typically stable & capable
• Process upsets last few cycles
• Defects found in next manufacturing step or location increase cost exponentially
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Motivation for Real Time Release
Defect Present
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Process – Simple Overview
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Process Step
Typical Injection Molding Process used to produce most plastic components© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Long Term Plan
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Scientific or Decoupled process validation
Controlled Cycle Sheets & Verification
100% cavitation, 100% of the time
Correct Process Monitoring Sensors
Hourly Shot Inspections
Lean Visual Management
Steel Certification
Training
Real-Time Release
Foundation for Success
Complete
Goal
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Long Term Plan
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Use Multivariate Statistics to fingerprint our processes to achieve Real Time Release
Utilization of Six-Sigma type approach for Process Understanding
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Design Space for a Molding Process
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Capturing the physics of the process and translating into phases
Basic Inputs captures dynamicsNozzle TemperatureZone 1 TemperatureZone 2 TemperatureZone 3 TemperatureInjection Pressure
Screw PositionCycle Time
Fill TimePack Time Plasticate Time
Calculated Data FeaturesFill Time
Pack/Hold TimePlasticating Time
Cooling TimeCycle Time
Start of FillingScrew distance during Filling Stage
Screw Distance during Packing/Holding StageScrew distance during Cooling Stage
Average Screw Velocity during Filling StageAverage Screw Velocity during first 5% of Packing Stage
Average Screw Velocity during Packing StageAverage Screw Velocity during Plasticating
Maximum Injection Pressure during Filling StageMaximum Injection Pressure during Packing Stage
Average Injection Pressure during Filling StageAverage Injection Pressure during Packing Stage
Average Injection Pressure during Plastication StagePlastication energy measured during plastication
Average viscosity during fillingAverage viscosity during plastication
Average Nozzle TemperatureAverage Zone 1 TemperatureAverage Zone 2 TemperatureAverage Zone 3 Temperature
Integral of Injection Pressure during fillingIntegral of Injection Pressure during packing
Integral of Injection Pressure during plasticationShot Cushion
Shot SizeOther variables as needed
Calculated
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Design Space for a Molding Process
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Trial Variable 1 Variable 2 Variable 3
1 -1 -1 -12 -1 -1 13 -1 1 -14 -1 1 15 1 -1 -16 1 -1 17 1 1 -18 1 1 19 0 0 0
RunVariable
1Variable
2Variable
3Variable
4Variable
5Variable
6Variable
71 -1 -1 -1 -1 -1 -1 -12 -1 1 1 -1 -1 -1 13 1 1 -1 1 -1 -1 -14 1 -1 1 1 -1 -1 15 -1 -1 -1 1 -1 1 16 -1 1 1 1 -1 1 -17 1 1 -1 -1 -1 1 18 1 -1 1 -1 -1 1 -19 0 0 0 0 0 0 010 -1 1 -1 1 1 -1 111 -1 -1 1 1 1 -1 -112 1 -1 -1 -1 1 -1 113 1 1 1 -1 1 -1 -114 -1 1 -1 -1 1 1 -115 -1 -1 1 -1 1 1 116 1 -1 -1 1 1 1 -117 1 1 1 1 1 1 1
+
Process Characterization methodology for our molding processes
Material & Process Relatedvariation Mold & Operator Related
variation
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Process Model
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• Process Model developed on calculated variables and using the two previous data sets
• Simple PCA type analysis found to be adequate for our process
R2 = 97% for this particular part
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Process Model
01/20/2011 14© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Process Model
01/20/2011 15© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Process Model - Implementation
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MVDA Engine
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Process Model - Implementation
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User interface that operators are trained to use
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Process Model - Validation
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Data collection system standardized for all machines
• SenseLink-QM system used
Validation / Verification process has been standardized for injection molding process
• Standard methodology for data collection
• Standard methodology for model development
• Standard methodology for verification & validation activities
Methodology is currently Mold / Machine / Stock Number specific
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Process Model - Results
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Results after implementation
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Process Model - Results
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Labor Hours – Quality
• Approximately 2000 hrs/year labor reduction achieved
• Production volume increase of 26%, without adding headcount– 2006 production volume = 486,463,916– 2008 production volume = 655,940,710
Exception Examples
• Greater than 90% reduction in exceptions on some machines with Real Time Release implemented
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Process Model - Results
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Faster Machine startup
• 40 changeovers / month average in 2006
• 66 changeovers / month average in 2008
• Process model ensures process settings, enables faster startup
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Process Model - Results
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Process Knowledge
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Process Knowledge Gained
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Real Time data allows us to detect things like supplier related issues much faster
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved
Process Knowledge Gained
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Real Time data allows us to detect things like intermittent hardware failures
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0 1000 2000 3000 4000 5000 6000 7000
Subgroups
Target
3 SD
3 SD
LCL(EWMA)
UCL(EWMA)
Side 1 10-13-05.M1 (PCA-X)EWMA/Shewhart (Subgroup 1): XVar(Var_6)
SIMCA-P+ 11 - 10/13/2005 8:02:08 PM
S(M1) = 1.028 Target(M1) = 43.76 S(EWMA) = 0.2116 UCL(EWMA) = 44.4
LCL(EWMA) = 43.13 Lambda = 0.08125
Process Knowledge Gained
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Impact of raw material changes
Process shifts, consistently every 2.5 – 3 hours
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Material leakage due to nozzle slip-back
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Process Knowledge Gained
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved01/20/2011
Summary
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Many parallels exist between Pharma & Device Manufacturing
• QbD & PAT methods can be implemented in both arenas
• Real Time Release increases process knowledge & understanding
• The information age has allowed us both access to critical data at low cost
• Real Time Release is possible in subassembly manufacturing operations
• Increased knowledge leads to safe, effective products and a better patient outcome
At the end of the day, it is really about the difference we make in our patients lives
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THANK YOU FOR YOUR ATTENTION
Lee Hutson
© Copyright 1995 – 2011 Baxter Healthcare Corporation All rights reserved