FAILURE FAILURE INVESTIGATION AND INVESTIGATION AND

ROOT CAUSE ROOT CAUSE ANALYSISANALYSIS

Presented By

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sLearning Objectives

Understand the Definitions of Failure Investigation and Root Cause Analysis (RCA)Introduce a common Failure Investigation and RCA ProcessDefine 1271 Regulatory Requirements Related to Failure Investigation and RCAUnderstand When and Where to Apply Methods and Tools

Tool Introduction and PurposeBest Practices

Provide Guidance on Documentation of Activities

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DefinitionsDefinitions

Failure Investigation - The process of understanding the key attributes of a particular failure and identifying the likely causes of failure.

Root Cause Analysis – The process of conducting an analysis to identify the physical, human, and latent causes of a particular undesirable event.

Root causes are specific underlying causesRoot causes are those that can reasonably be identifiedRoot causes are those that are controllable and fixableRoot causes are those where prevention is possible

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Regulatory Requirements

When is it REQUIRED to formally investigate (and perform root cause analysis)?

1271.160 (b)(2) “Ensuring that procedures exist for receiving, investigating, evaluating, and documenting information related to core CGTP requirements, including complaints…”1271.160 (b)(3) “Ensuring that appropriate corrective actions relating to core CGTP requirements… Documentation must include, where appropriate; (ii) The nature of the problem requiring corrective action;”1271.160 (b)(6) “Investigating and documenting HCT/P Deviations and trends of HCT/P deviations relating to core CGTP requirements…”1271.230 (a) “Procedures. You must establish and maintain procedures for review, evaluation and documentation of complaints…and the investigation of complaints as appropriate.”1271.230 (b) “Complaint File. … The complaint file must contain sufficient information about each complaint for proper review…and for determining whether the complaint is an isolated event or represents a trend.”

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Regulatory Requirements

When is it REQUIRED to formally investigate (and perform root cause analysis)?

1271.320 (c) “Review and evaluation of complaints…. As soon as practical, you must review, evaluate, and investigate each complaint that represents an event required to be reported to FDA… You must review and evaluate a complaint relation to core CGTP requirements that does not represent an event required to be reported to determine whether and investigation is necessary… When no investigation is made, you must maintain a record that includes the reason no investigation was made….”1271.350 (a) “Adverse reaction reports. (1) You must investigate and adverse reaction involving a communicable disease related to an HCT/P that you made available for distribution.”1271.350 (a)(3) You must, as soon as possible investigate all adverse reactions that are the subject of these 15-day reports…”1271.350 (b) Reports of HCT/P deviations. (1) You must investigate all HCT/P deviations related to a distributed HCT/P for which you performed a manufacturing step.”

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Process OverviewKey Process Steps

General Problem Identification Gather / Create SamplesFailure Investigation and Experimentation

Examination / Dissection / Physical TestingCausal Factor Identification

BrainstormingUse of tools (fishbone, causal factor chart)

Hypothesis DevelopmentLinking Analysis Data to Causal Factors

Hypothesis TestingDOE / ANOVA / Simple VerificationStatistically Based Methodology

Root Cause IdentificationRoot Cause Map

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Process Flow Chart

General ProblemIdentification and

Basic ProblemStatement

Gather / CreateEvaluationSample(s)

Failure Investigationand Experimentation

Causal FactorIdentification

HypothesisDevelopment

OutcomeConsistent

withProblem

Statement

Revise / ClarifyProblem Statement

to be Specific

Hypothesis Testingand Verification

DataConsistent

w/Hypothesis

Data Analysis

Revise Hypothesis

Final RootCause

Identification

Start

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Failure Investigation

Common Tools / ActivitiesSample DissectionRepresentative / Worst Case Sample CreationPhysical, Chemical, Human Factors Testing and AnalysisEnvironmental Stress ScreeningProcess CharacterizationProcedural Review

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Root Cause Analysis

Common Tools / AnalysisFishbone DiagramsPareto Charts, Run Charts, other Control Chart MethodsANOVA and Design of ExperimentsCausal Factor ChartingRoot Cause Map

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Basic PointsUse common sense

Use tools when they support a comprehensive analysis, not just because they are available.

Right-Size the Investigation / Analysis – be sure not to make the problem more complicated than necessary Avoid ANALYSIS PARALYSISAnalyze the likely causes FIRSTUse feedback loops to refine problem statement and causal analysisMost problems have more than one root causeDon’t be afraid to ignore the instructions

Use the tools in a way that make sense for the problem. Tools are generic and may need to be modified to fit your situation.

The problem dictates the tools, not the other way around

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Problem Identification

Draft Problem StatementBegin the process with a simple statement of the problem.Do not define the cause in the problem statement. Keep an open mind.

Create / Gather SamplesGather evidence showing the existence of the problem.

Product ReturnsCollecting DocumentsCreation of discrepant samples

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Problem Identification

Sample EvaluationSamples may be tissue products, packaging, test results, records, etc.Product Review

Sample DissectionPhysical Testing

ChemicalMicrobialPhysicalFunctional

Records ReviewDatesChangesRelationship to other relevant recordsChronology / HistoryInterviewsDuplicates in other locations

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Problem dentification

Problem Statement RevisionInspection / Testing / Review

Are results consistent with Initial Problem Statement?Updated Problem Statement

Change ScopeExpand ScopeReduce Scope

BE SPECIFIC based on observable data

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Identify Likely Causes

Utilize Analysis ToolsCause and Effect (Fishbone) DiagramCausal Factor ChartProcess Flow Chart

BrainstormDo not rule out causes or assess likelihoodLook at all elements of the processWhen in doubt start with 5 standard categories

ProcessEnvironmentMaterialsHuman FactorsEquipment

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Cause / Effect Diagram

Bag SealFailure

Process Environment

Equipment Human FactorsMaterials

Lack ofProcedure

Detail

NotCalibrated

Design

Installation

Particulate

Humidity

TemperatureCleaning

WrongMaterial

WrongThickness

Contamination

Maintenance

Reliability

Training

Workload

Complexity

EnvironmentStorage

Filters Doors

De-humidifier Source Air

HVAC Other Src.

Writing Skills Valiation

No Procedure Late

No Procedure Chemical

Supplier Error Spec Error

Process Mixup

Environment Cleaning

HeatingElement

PressureControl

Air Pressure ElectricalSupply

Not Executed WrongProcedure

ControllerFailure

Operator Cirriculum

Overtime

Distraction

Setup Operation

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Hypothesis Development / Testing

Causal AnalysisIdentify list of most likely causes (top 3 to 5)

Develop / utilize a rating scale or rating scheme (i.e. – hazards evaluation)Be specific so that the contribution of each cause can be evaluated

Hypothesis DevelopmentDevelop one or more scenarios to describe the failure based on the failure investigation data and the causal analysisMust be able to be evaluated / tested

Hypothesis Testing / EvaluationSimple Inspection / Review of DataExperimental DesignWorst Case AnalysisANOVADOE

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Hypothesis Development / Testing

Data AnalysisAppropriate Statistical MethodsDoes the Data Support the Hypothesis?

Yes – Continue to Corrective / Preventive ActionNo – Revise Hypothesis or Causal AnalysisMaybe – Further Experimentation is necessary

Hypothesis RevisionRevise Causal Analysis based on Experimental ResultsRevise Hypothesis StatementRetest as Necessary

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Pareto Charts

Calibration Errors

1326 31

4451

92

0102030405060708090

100

Janu

ary

Februa

ry

March

April

May

June

Month

Nor

mal

ized

Qua

ntity

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tControl Chart

Average Production Hours

40 40 40 40 4044 46 46

50 50

59

50

39 4040

253035404550556065

22 24 26 28 30 32 34 36

Week Number

Hou

rs Mean

UCL

LCL

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Misc. Charts

Bar Temperature by Position

226227228229230231232233234235236

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Position

Tem

pera

ture

(C)

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Root Cause IdentificationSummarize Results of Hypothesis Evaluation

Identify all root causes that significantly contribute to failureIdentify significant interactions between root causesPrioritize root causes based on impactDevelop recommendations for:

Corrective Action (remedial action to correct items / units / tissues already exhibiting failure)Preventive Action (action to prevent recurrence of the problem)

Formally Document the Results

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Root Cause Summary Table

Bag Seal Failure Root Cause Analysis Summary TableRoot

Cause ID DescriptionImpact (H/M/L) Siginificant Interactions Recommendations

1 Temperature Variation on Sealer Bar H

Temperature variability increases dramatically with decreased sealing

cycle timeReplace sealer bar, increase calibration

frequency, perform validation

2 Sealer Cycle Time HDecreasing cycle time increases

temperature variation on sealer bar Specify minimum cycle time as 30s in SOP

3 Material Thickness M

Lower end of current specification does not seal correctly at highest temperature

seen on sealer barRevise specification, implement thickness

measurement at RI

4 Accuracy of Calibration MCalibration variation accounts for 20%

of overall bar temperature variation

Revise instrumentation specifications for use during sealer calibration. Improve

instrument accuracy to 1:10 ratio

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Documentation

Failure Analysis / Root Cause Analysis can be included in:

Complaints / Adverse Reactions / HCT/P DeviationsInternal Deviations (Errors, Incidents, Accidents)Validation FailuresInspection Failures / Non-Conforming ProductOther Corrective / Preventive Action Projects

Key Elements of DocumentationSpecific Problem StatementTraceability / Tracking Information

FailuresTest Samples

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Documentation

Key Elements of Documentation (cont.)Failure Investigation

Observational / Inspection DataTest Information

ProtocolData AnalysisResultsConclusions

Causal Factor IdentificationHypothesisHypothesis Testing and Verification

ProtocolData AnalysisResultsConclusions

Root Cause Summary (report, table, etc.)

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Documentation Points to ConsiderHow detailed do I need to be in my documentation?

Detailed enough so that someone from the outside can follow your logic and could replicate your results.Detailed enough to meet specific regulatory requirements (i.e. – complaints, adverse reactions, HCT/P deviation)

Do some areas need to be more detailed than others? If so, what areas should I emphasize?

Yes:Problem DescriptionTraceabilityFailure InvestigationRoot Cause Summary

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Documentation Points to Consider

Do I have to go through every step for every investigation?No, use common sense and right-size the activities for the project.Wherever the term “investigation” is used in a regulation or standard, a certain level of rigor is implied. Again, focus on:

Problem DescriptionTraceabilityFailure InvestigationRoot Cause Summary

For Complaints (not reportable to FDA), when can I avoid doing an Investigation and Root Cause Analysis?

When a similar complaint has been fully investigated and you can refer to such an investigation.When the event, based on documented data analysis, is an isolated event and does not represent a trend (this does not relieve requirements for review and evaluation for complaints related to core CGTP requirements.)

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Documentation Points to Consider

When in doubt, write it down!If you were an Auditor, what would you want to see to ensure activities were done correctly?If CAPA is done by another group or person, what will they need to complete the project?If I were gone, would someone be able to follow my process and reach the same conclusion?