sslean validation 20070622

© Cordis Corporation 2004 155-2862-1 1

Six Sigma and Lean Tools for Validation

Jan C. Crielaard, Principal, WW Validation Cordis Corporation, a Johnson and Johnson Company

Pharmaceutical Technology’s Annual ConferenceJuly 23-25, 2007 - Park Hyatt at the Bellevue - Philadelphia, PA


Agenda

• Validation life cycle and Six Sigma methodologies – Concepts and Definitions– Basis for Process Validation

• Utilize Lean tools to assess validation system efficacy and efficiency – RACI analysis– Group Technology and Job Standardization– Value Stream Map– Gauge RnR


Agenda

• Control plans and validation metrics– Purpose of control plans– Metrics / Quality Indicators– Dashboards

• Interactive Exercise: – Facilitating a transactional Kaizen initiative.


Learning Objectives

• Provide common terminology• Understand GMP evolution and how it relates to

Six Sigma• Introduce selected Six Sigma tools and present

how they can be applied to validation• Introduce selected LEAN tools and apply these

tools to assess and improve validation systems


Validation life cycle and Six Sigma methodologies


Minimize risk to the public health associated with pharmaceutical products by:– Encourage implementation of risk-based

approaches for industry and FDA– Encourage continuous improvement

FDA’s Initiative GMPs for the 21st Century


– Focus on variability reduction through process understanding

– Focus on detect, analyze, correct and prevent problems

FDA’s Initiative GMPs for the 21st Century


• To improve efficiency by optimizing a process and eliminating wasted efforts in production

• Focus lays on reducing variability in process and product quality characteristics and are not for changing the fundamental design of a manufacturing process (FDA, page 20)

• Achieving and maintaining a state of control for process begins at the process development phase and continuous in entire product life cycle

• Quality should be built into the product

Continuous Improvement FDA


Six Sigma

• A systematic approach for continuous sustainable Improvements

• Define phase: Clear problem understanding • Measure phase: Establish Baseline• Analyze phase : Identify key drivers• Improve phase : Manipulate key drivers for optimal solutions• Control phase : Strategy to maintain gains

Measure

AnalyzeImprove

Control

Define


DMAIC tool overview

· Benchmark· Baseline· Voice of the

Customer· Process Flow

Map· Project

Management

Define Measure Analyze Improve Control

· Defect Metrics· Data

Collection, Plan, Logistics

· Sampling Techniques

· Cause & Effect Diagrams

· FMEA· Risk Analysis· Control Charts· Capability· Reliability· Root Cause

· Design of Experiments

· Modelling· Tolerancing· Robust Design

· Statistical Control

· Preventative Activities

· Verification· Effectiveness


Causal thinking y = f(x1, x2,…, xn)

Cause-and-Effect Diagram

Process output

Machine

MenMaterialsMother Nature

MeasureMethodMachine


MeasureMethod


Risk Based approach

• Is a paradigm focused on testing those aspects that can affect the product quality

• Requirements:– A proper and true understanding of the system– The ability to identify and asses product risk inherent to the manufacturing

process, Risk Management

Traditional

• Inputs/outputs determined at time of validation

• Validation used to catch issues

• All facility, utility and process equipment and components are validated

Risk-Based

• Inputs/outputs transferred from design to validation

• Validation used to confirm requirements

• Validate equipment and components that have potential impact to product quality


Risk Management

•The process of measuring or assessing risk and developing strategies to manage it

•Guides the setting of specification and process parameters for manufacturing, assess and mitigate the risk of changing a process or specification, and determine the extent of discrepancy investigation and corrective actions

•Risk management is an iterative process, it should be repeated when new data becomes available

•Controls commensurate with level of risk


Risk Management

Production

monitoring

Risk Estimation

Risk Evaluation

Risk Control


Risk Estimation

•Risk estimation is a way to quantify the risk associated with each cause of each hazard identified

Tools:

•Fault Tree Analysis (FTA)

•Failure Mode Effects Analysis (FMEA)

•Hazard Analysis and Critical Control Points (HACCP)

•Failure Mode Criticality and Effects Analysis (FMCEA)

•Hazard Operability Analysis (HAZOP)

•Control HAZOP (CHAZOP)


FTA

• Top down approach:

Given a potential Hazard,

determine the possible drivers

of failure

• Each failure mode may have its own failure mode

• Continue till individual sources are identified

Identify Hazards

Identify all potential failure modes

Diagram the fault tree

TEAM

EFFORT


FTA

Inadequate control body

temperature

Machine


MeasureMethod

Inaccurate Temp reading

Cooling mech ineff.

Inadequate control body

temperature

Machine


MeasureMethod

Inaccurate Temp reading

Cooling mech ineff.


FMEA• Bottom-up-approach:

Given a system,determine potential

hazards by asking what can go

Wrong

• Focus on how and under which circumstances system will fail

• Focus not if system will fail

Identify component or process steps

Identify what can go wrong

Determine Effect for user

Score•Severity

•Occurrence•(Detectability)

Evaluate the risk &identify controls and mitigation

actions

T

E

A

M

E

F

F

O

R

T

Functional Component Failure Mode

User Harm S

ev

Occ

Det Control

Temp sensor Drifts low

Body temp too low 9 2 2

Accuracy Testing

Cooling Mech

Underpowered coolant

Body cools to slow 5 6 6 Test loop


Impact Assessment *

Impact assessment characteristics:• Bottom-up-approach• Specific criteria build around families of potential failure

modes• Criteria are common to Pharmaceutical systems• Assessment on system and component level

* ISPE, Pharmaceutical Engineering Guides for New and Renovated Facilities


System Impact Assessment*Criteria indicating “Direct Impact “

1. The system has direct contact with the product

2. The system provides an excipient, or produces an ingredient or solvent

3. The system is used in cleaning or sterilization

4. The system preserves product quality

5. The system produces data which is used to accept or reject product

6. The system is a process control system that may affect product quality and there is no system for independent verification of control system performance in place



Component Criticality Assessment*

Criteria indicating “Criticality “

1. The component is used to demonstrate compliance with the registered process

2. The normal operation or control of the component has a direct effect on product quality

3. Failure or alarm of the component will have a direct effect on product quality or efficacy

4. Information from this component is recorded as part of the batch record, lot release data, or other GMP-related documentation



Component Criticality Assessment*

Criteria indicating “Criticality “

5. The component has direct contact with product or product components

6. The component controls critical process elements that may affect product quality, without independent verification of the control systems performance

7. The component is used to create or preserve a critical status of a system



Impact Assessment

Systems and Components

ImpactAssessment

CommissionSystem

Intended Use

Change Control

Change ControlEvaluation

DesignDocuments

Requirements

Indirect Direct

System Boundaries

Industry Guides

Hazard Analysis

FMEA

No Impact

Good Engineering Practice

Commission and Qualify system


Risk knowledge

• Drives Design - e.g.”Design for impact”

• Establishes qualification requirements• Drives Acceptance Criteria• Establishes baseline for (Change Based)

revalidation


Utilize Lean tools to assess validation system efficacy and efficiency


Overall approach

Principle: Map current state (data and facts)

Purpose:

Analyze - Identify improvement opportunities based on current performance:– Compliance– Efficiency

Outcome: Map future state (new process, targets)


Tools

• RACI analysis• Group Technology and Job Standardization• Value Stream Map (VSM) • Gauge RnR (Attribute)


RACI Analysis

Purpose: Identify and optimize:• Responsibility• Accountability• Consult• Information

1 Map current stateDepartment

Role

Wa

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ou

se

Ma

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ge

r

En

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r

Tech

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ian

Dir

ect

or

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Ad

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or

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Dir

ect

or

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ee

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Op

era

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Dir

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or

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En

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Tech

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Verification of build prerequisites A R IPreparation for Execution A R C I IComponents and Raw Material on warehouse A R C IComponents and Raw Material Released A R I I ITools and Equipment Calibrated I I I A RTesting Equipment Identified A RConsumables as required per SOP's I A RVerify Certification of personnel involvedValidation procedure A R I CCalibration Procedure A R I CPM Procedure A R IDocuments Released Before Units ManufacturingBill of Material released C ASOP Released or Draft A RAnalytical and Test Method Validations A RSpecifications / Acceptance criteria A RPreparation of the Equipment Set-up the Equipment Parameters according to SOP R/AVerification of Tools availability according to SOP R/Aetc….

CalibrationOperationsWarehouse Training Engineering Quality


RACI Analysis

2 Analyze / Improve• R and A defined for each task• Consistent approach• Minimize duplicate roles• Combine C and R role where possible• Align A and R to organizational structure• Etc.

3 Map future state• Integrate in procedures

Typical improvement opportunities• Responsibilities not defined• More than 1 person responsible• Approvers that only need to be informed


Group Technology Analysis

• Identify similar tasks• Identify common groups• Optimize the validation process based on largest

common groups



• Identify common elements based on completed validations

Grouping property 1Grouping property 2Grouping property 3Grouping property 4Grouping property 5

Document numberCommon element 1 2 3 4 5 6 7 8 9 0 11 12

Approval (to Execute)

Approval Statement x x x x x x x x x x x xpersons x x x x x x x x x x x xtitles x x x x x x x x x x x xPurpose

Reason for the validation x x x x x xExpected outcome x x x x x x x xresults and conclusion x xStatement : applicable IOQ's have been completed xStatement: report contains the results of…. x

Scope

Process in scope x x x x x xProduct/part in scope x x x x x x x x x xSystem Identification x x x xProduct matrix of all catalog numbers in scope x x x x x x x x x xLocation x x x x x x xStrategy Reference x x x x x x x xListing of processing elements x



• Analyze data to identify groups (patterns, %)

All%

Allprotocols

%

Allreports

%Facility Equipment Utility

Common elementApproval (to Execute)

Approval Statement 100 100 100 100 100 100persons 100 100 100 100 100 100titles 100 100 100 100 100 100Purpose

0 0 0 0 0 0

Reason for the validation 54 90 46 25 33 100Expected outcome 69 100 33 100 33 100results and conclusion 23 0 0 0 100 0Statement : applicable IOQ's have been completed 8 14 0 25 0 0Statement: report contains the results of…. 8 0 33 0 0 0Scope

0 0 0 0 0 0

Process in scope 8 14 0 25 0 0Product/part in scope 54 57 33 75 67 33System Identification 85 86 67 75 100 100Product matrix of all catalog numbers in scope 31 29 33 25 33 33Location 77 100 100 100 0 100Strategy Reference 62 71 67 50 33 100Listing of processing elements 62 86 33 100 33 67

GROUP TECHNOLOGY ANALYSIS


Job Standardization

• Develop standard process for common groups.• Focus improvement initiative on occurrence:

System Type

EQUIPMENT87%

UTILITIES11%

FACILITIES2%


Job Standardization

Change Type

MOVE EQUIPMENT33%

UPGRADE EQUIPMENT13%

UPGRADE SOFTWARE13%

NEW EQUIPMENT11%

EXISTING EQUIPMENT6%

MINOR TOOL MODIFICATION6%

UPGRADE ROOM2%

NEW UTILITIES2%

REPAIR EQUIPMENT3%

NEW TOOL 5%

MOVE LINE DIFFERENT BUILDING

6%

Same Type of Validation

• Develop standard process for common groups.• Combine groups with similar common elements:


Group Technology Analysis (Compliance)

• Identify common elements based on internal and external requirements

pro

toco

lfo

rma

t

rep

ort

form

at Internal procedure

#1

Internal procedure

#2

Internal procedure

#3

Internal procedure

#4

1987 FDA Guidance

GHTF.SG3 N99-10(2004)

Common elementApproval (to Execute)

X X

Approval Statement X Xpersons x xtitles x x x xPurpose

X X

Reason for the validation x xExpected outcome x x xresults and conclusion

Statement : applicable IOQ's have been completed

Statement: report contains the results of….

ScopeX X

Process in scope

Product/part in scope x xSystem Identification x xProduct matrix of all catalog numbers in scope xLocation

Strategy Reference xListing of processing elements x


Group Technology Analysis (Compliance)

• Improve alignment to regulatory requirements• Remove non value added elements /

requirements from existing procedures


Value Stream Map (VSM)

• ‘Walk the actual process’ (not the procedure)• Map the process• Identify and collect critical metrics


Current state VSM

176 hrs

I dle Time = 288 hrs(36 days)

Processing Time = 386 hrs(48 days)

Product Development Team

Tact Time = 1.7 Days(includes PQ Protocol &

Report)

1 hr 160 hrs 1 hr80 hrs

PQ Report Approval

9

Generate PQ Report

1

20 daysC/T

Y ield N/A

Protocol Execution

27

10 daysC/T

Y ield 30%

PQ ProtocolApproval

8

1 hour (est)C/T

Y ield 27%

Generate PQProtocol

1

18 daysC/T

Y ield N/A

DesignCharacterizationSummary Report

Released

1 min (est)C/T

Y ield N/A

1 hour (est)C/T

Y ield 28%

56 hrs

144 hrs0

PQ Current StateValue Stream Map

IProtocol in Sign-

Off(7 days)

IDelay f or product

build(22 days)

IReport in Sign-

Off(7 days)

148 PQ’s per YearDemand

Available Time

Days per Week

Weeks per Year

250 Days per Year

50

5

0(cPDM)

56 hrs


Brainstorm improvement opportunities

‘Kaizen bursts’• Green: Implement now• Yellow: Get more data• Red: Implement later


VSM – Kaizen Bursts

176 hrs





Report)


PQ Report Approval

9

Generate PQ Report

1

20 daysC/ T

Y ield N/ A

Protocol Execution

27

10 daysC/ T

Y ield 30%

PQ ProtocolApproval

8

1 hour (est)C/ T

Y ield 27%

Generate PQProtocol

1

18 daysC/ T

Y ield N/ A


Released

1 min (est)C/ T

Y ield N/ A

1 hour (est)C/ T

Y ield 28%

56 hrs

144 hrs0


xxxx

Sign-Off meetings?Other methods f ormanaging approvalprocess; Perf orm

VOC with eff ectiveteams

IProtocol in Sign-

Off(7 days)

IDelay f or product

build(22 days)

IReport in Sign-

Off(7 days)

I mprove yieldthrough standardprocess outputs


Available Time

Days per Week

Weeks per Year

250 Days per Year

50

5

Simplif y deviation process;defi ne what is a deviation;

mistake-proof documentXxxx system to prevent

certain types of deviations;electronic f orm routing

0(cPDM)

56 hrs

PQ ReportGenerator (xxxor xxx f ormat)

I mprove yieldthrough standardprocess outputs

Ensure that all inf ois available and

prerequisites aremet prior to

initiating protocol -Checklist

Clarif y inf orequired – use

more tables!

Expertise ofdocument authors –

xxx training;dedicatedresources?

Train project leaderson validation projectmanagement; provide

skeleton planReview

approvalmatrix

Checklist f orreviewer

responsibility

Pareto of rejectreasons – what

are primaryopportunities?

Establish pre andpost-sterile

correlation incharacterization sothat PQ testing canoccur pre-sterile

Projectplanning f or

lab resources

Establishbasic testing

capabilities ateach site

Write procedurewith appropriate

detail f orexecution – xxx

concept?

Eliminateredundantinf ormation

f rom protocol

Pareto of rejectreasons – what

are primaryopportunities?


Future State VSM

• New process design / lay-out• Targets


Future state VSM

176 hrs





Report)


PQ Report Approval

9

Generate PQ Report

1

2 daysC/ T

Y ield N/ A

Protocol Execution

6

10 daysC/ T

Y ield 90%

PQ ProtocolApproval

4

1 hour (est)C/ T

Y ield 90%

Generate PQProtocol

1

2 daysC/ T

Y ield N/ A


Released

1 min (est)C/ T

Y ield N/ A

1 hour (est)C/ T

Y ield 95%

56 hrs

144 hrs0


IProtocol in Sign-

Off(2 days)

IDelay f or product

build(10 days)

IReport in Sign-

Off(2 days)


Available Time

Days per Week

Weeks per Year

250 Days per Year

50

5

0(cPDM)

56 hrs


Gauge RnR (Attribute)

Can be applied to the transactional process.

Basic steps:• Map the process and Identify all possible outcomes of the

process• Design gauge RnR• Develop different scenarios• Develop repeats (alternative description of scenarios)• Have different users evaluate the different scenario’s

(blind)

• Analyze the variation


Gauge RnR

Identify all possible

outcomes of the

transactional process


Gauge RnR

Design gauge RnR

2 people 5 scenarios 4 repeats

Joe Sally

Scenarios 1 2 3 4 5 1 2 3 4 5

repeats 1234 5678 .… .… .… …. 1234 5678 .… .… .… ….


Gauge RnR

Few examples of different scenarios

(Process for handling deviations):• You are analyzing the data from a PQ, and you realize that the

statistical method prescribed in the protocol is not appropriate. You can use the existing data, but you decide to use a different statistical method for the analysis.

• You are conducting a PQ test, and you accidentally drop one of the test units on the floor and damage the unit. You decide to replace the test unit with an extra unit from the same lot.

Repeat:• You accidentally scratched the surface of a test unit. Since there are

sufficient units in the lot, you decide to take a new unit from the lot and use this for testing.


Gauge RnR

Analyze the variation in the study results to determine:• Do appraisers classify the same scenario in the same way

each time? (% Matched Within Appraiser)

• Did each appraiser correctly classify the scenario as compared to the standard? (% Matched Appraiser vs. Standard)

• Do the appraisers’ classification agree with each other? (% Matched Between Appraisers)


Analyze data

What about:

• Scenario number 1?

• Scenario 2?

• Scenario number 5?

2 people 5 scenarios 4 repeats

Minitab: Stat>Quality Tools>Attribute Agreement Analysis

Scenario Appraiser Repeat Measurement Standard Scenario Appraiser Repeat Measurement Standard1 Joe 1 1 1 4 Joe 1 3 3

Joe 2 1 1 Joe 2 3 3Joe 3 1 1 Joe 3 3 3Joe 4 1 1 Joe 4 3 3Sally 1 1 1 Sally 1 3 3Sally 2 3 1 Sally 2 3 3Sally 3 1 1 Sally 3 3 3Sally 4 1 1 Sally 4 3 3

2 Joe 1 1 2 5 Joe 1 5 5Joe 2 1 2 Joe 2 5 5Joe 3 1 2 Joe 3 5 5Joe 4 1 2 Joe 4 5 5Sally 1 2 2 Sally 1 5 5Sally 2 2 2 Sally 2 3 5Sally 3 2 2 Sally 3 5 5Sally 4 2 2 Sally 4 5 5

3 Joe 1 4 4Joe 2 4 4Joe 3 4 4Joe 4 4 4Sally 1 4 4Sally 2 4 4Sally 3 4 4Sally 4 4 4


Considerations for an Attribute Gage R&R Study

– Clear and concise operational definitions are critical

– Each person makes a decision (pass/fail, 1,2,3,4.., etc.) for each scenario repeatedly

– The scenarios should represent the range of variation in the process

– People should make random and “blind” decisions; they should not know which scenario they are reviewing when they record their results

– Data must be balanced for Minitab—each person must decide each scenario the same number of times


Control Plans and Validation Metrics


Control Plan - Purpose

Classical: Maintain the validated state– Change Control– APR / Periodic Review – Time based re-validation

SixSigma: Enable effective decision making“what gets measured gets managed”– Maintain performance level (set targets)– Identify improvement opportunities– Sustain gain


Metrics

Classical: Reported as part of the Quality System – Metrics rolled up in Quality Management Review

SixSigma:– Based on causal thinking

Process output

Machine


MeasureMethodMachine


MeasureMethod


Causal thinking y = f(x1, x2,…, xn)

Causal Driver Hierarchy

Process output

Drivers (x’s)Dirver of Drivers (x’s)

xxxxx …xxxx … x

xxxx … x

x

...

Process output

Drivers (x’s)Dirver of Drivers (x’s)

xxxxx … xxxx …xxxx … xxxx … x

xxxx … xxxxx … xxxx … x

x

......


Useful Metrics

A metric is:• A standard or unit which can be measured• The dimension, capacity or amount of something• A means to assess performance

Specific/Systematic (linked to business needs)Measurable/MeaningfulAgreed-upon/ActionRelevant/ Rooted in factsTangible/Thoughtful


Balanced Metrics

Leading vs.. Lagging• Causal Effect drivers are leading and may be used for

a proactive approach e.g analysis, decision making and corrective actions

• Indicators measured near or at the end of process are lagging, they are useful for overall analysis but they lag the Causal effect link

Effectiveness vs.. Efficiency• Effectiveness is a metric for the result of a process• Efficiency expresses the capability of that process• Both are required to express the success of a process

(optimizing one often adversely affects the other)


Balanced Metrics

Leading

Lagging

Effectiveness

Efficiency

Supplier

Input Metrics

CustomerOutputProcessInput

Output MetricsProcess Metrics

X X

X

X XX

X

Examples:

•Leading: % engineer trained against validation procedures

•Lagging: % reject protocols

•Effectiveness: Validation related audit observations

•Efficiency: % of validation first time right


Dashboard Causal driver Hierarchy

Tactical

Strategic

More frequent

Less frequent

Linkage / Focus

Frequency of review

Mission: Compliant validations in an efficient manner

Key Outcome Measures (y's)

Strategic Objectives

# ObservationsValidation throughput

time/ Yield

Compliancy Efficiency

Key Drivers Measure (x's)

Approvaltime

Executiontime

# Reviewiterations

#Deviations

Responsetime

% trainedengineers

# Audits

# Fieldcomplaints

# NCR

# Test cases% trainedengineers


Features of a Well-Dressed Dashboard

# of Reviews

LCL and UCL

Average

Benchmark

Review

iterations

TimeF M A J J A

2

4

6

8

10G

oodQuick reference legend

i.e. “Trend down=Good”

Clean Data Display:Average and control limitsTrend and goal

Title X and Y axis

Chart legend andupdate frequency

DescriptionThis dashboard shows the number of iterations average per month.

The benchmark of 2 iterations is the goal.

ExplanationMore then 1 review means rework. Rework is waste. Waste needs to be minimalized.

Action planDescending trend is good.

Ascending is bad, requires root cause analysis and preventive action.

Description, Explanation and action plan


Interactive Exercise: Facilitating a transactional Kaizen initiative

改善


What is Kaizen

What is Kaizen ? ( 改善 - ky’zen)

• “Kai” means “change”

• “zen” means “good (for the better)”

• Gradual, orderly, and continuous improvement

• Ongoing improvement involving everyone

Kaizen is the lean manufacturing term for continuous improvement and was originally used to describe a key element of the Toyota Production System.


What is Kaizen

• Kaizen describes an environment where functional areas and individuals proactively work together to improve processes.

• Kaizen events focus resources and employees on a specific area to achieve real process improvements in a short period of time.


What is Kaizen

Most Kaizens have these common features:• Focus on making improvements by detecting and

eliminating waste• Use a problem solving approach that observes how the

process operates, uncovers waste, generates ideas for how to eliminate waste, and makes improvements

• Use measurements to describe the size of the problem and the effects of the improvement

Tools: Six Sigma and Lean Tools: Six Sigma and Lean


The benefits to applying Kaizen

• Solutions emphasize commonsense low-cost approaches,

Thus,• Continual adjustment and improvement becomes

possible and further desirable.

Creativity before capital!Creativity before capital!


Transactional Kaizen

• Improvement opportunities in transactional processes:

• Simplify/streamline processes• Reduce lead times• Eliminate mistakes/rework

All these alternatives can be combined in a broad improvement plan.All these alternatives can be combined in a broad improvement plan.


Scope of transactional Kaizen

• Goals must be 100% achievable during the Kaizen Event

• Results must be quantifiable• Must meet the business objectives of the

organization


Event Format

• Clear expectations• Start times & end times• Dedicated participation• There are no bad ideas• Transparent roles & responsibilities


Activity Flow

Review Base

Condition

Identify

Waste

Problem

SolveCommunicat

e

Coordinate

Verify

Measure

Update

Job Standardizati

on

Present

Out-Brief

Implement

Solutions


1 week Kaizen using DMAIC approach

Day 1: Define• Training• Why are we here• Walk the process• Review existing data• Define goals and scope

Day 2-3-4: Measure and Analyze phases:• Investigate identified problems• Collect additional data• Solve identified problems• Identify waste• Develop Performance Metrics• Perform Risk Assessment• Pilot solution (if possible)• Identify Validation/Regulatory Requirements.

Measure

AnalyzeImprove

Control

Define


1 week Kaizen using DMAIC approach

Day 5 Improve phase:• Implement improvements• Eliminate waste• Implement Performance Metrics

Ongoing: Control phase :• Verify and Measure improvements

Measure

AnalyzeImprove

Control

Define


Conclusion

Kaizen events enable resources and employees to be focused on process improvements.

Questions?Questions?


Contact information

Jan C. Crielaard

Cordis Corporation, a Johnson and Johnson Company

E-mail: [email protected]


References

• A.I.A.G. Measurement Systems Analysis: Reference Manual. A.I.A.G., 1990 (Available from A.I.A.G. (313)358-3570)

• Wheeler, Donald J. and Lyday, Richard W. Evaluating the Measurement Process, Second Edition. Knoxville, TN: SPC Press Inc. 1989.


References

• ISPE, Pharmaceutical Engineering Guides for New and Renovated Facilities, Volume 5 Commissioning and Qualifications, first edition March 2001 www.ISPE.org

• IVT, Technical Guide, Six Sigma and Process Validation Strategies www.ivthome.com


References

• Siegfried Schmitt, The Manager’s Validation Handbook, Strategic Tool for Applying Six Sigma to Validation Compliance, PDA, DHI Publishing, ISBN 1-930114-84-2

• Don Tapping and Tom Shuker, Value Stream Management for the Lean Office Productivity Press, ISBN 1-56327-246-6


References

• Mike Rother, John Shook, Learning to See, value –stream mapping to create value and eliminate muda, version 3 The Lean Enterprise Institute, www.lean.org, ISBN 0-9667843-0-8

• Shigeo Shingo, Zero Quality Control: Source Inspection and the Poka-yoke System Productivity Press, ISBN 0-915299-07-0

sslean validation 20070622

Business

process validation

process control system

process equipment

level of risk

time of validation validation

validation system efficacy

iterative process

process of measuring