FAILURE

INVESTIGATION AND
ROOT CAUSE
ANALYSIS
Presented By
Clay Anselmo, R.A.C.
President and C.O.O.
Reglera L.L.C.
Denver, CO

Learning Objectives
Understand the Definitions of Failure Investigation
and Root Cause Analysis (RCA)
Introduce a common Failure Investigation and RCA
Process
Define 1271 Regulatory Requirements Related to
Failure Investigation and RCA
Understand When and Where to Apply Methods and
Tools
Tool Introduction and Purpose
Best Practices

Provide Guidance on Documentation of Activities

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Definitions
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 causes
Root causes are those that can reasonably be identified
Root causes are those that are controllable and fixable
Root 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 complaintsand the investigation of
complaints as appropriate.
1271.230 (b) Complaint File. The complaint file must contain sufficient
information about each complaint for proper reviewand 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 Overview
Key Process Steps
General Problem Identification
Gather / Create Samples
Failure Investigation and Experimentation
Examination / Dissection / Physical Testing

Causal Factor Identification

Brainstorming
Use of tools (fishbone, causal factor chart)

Hypothesis Development
Linking Analysis Data to Causal Factors

Hypothesis Testing
DOE / ANOVA / Simple Verification
Statistically Based Methodology

Root Cause Identification

Root Cause Map
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Process Flow Chart

Revise / Clarify
Problem Statement
to be Specific

Start

General Problem
Identification and
Basic Problem
Statement

Gather / Create
Evaluation
Sample(s)

Failure Investigation
and Experimentation

Hypothesis
Development

Hypothesis Testing
and Verification

Data Analysis

Outcome
Consistent
with
Problem
Statement

Data
Consistent
w/
Hypothesis

Revise Hypothesis

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Causal Factor
Identification

Final Root
Cause
Identification

Failure Investigation
Common Tools / Activities
Sample Dissection
Representative / Worst Case Sample Creation
Physical, Chemical, Human Factors Testing and Analysis
Environmental Stress Screening
Process Characterization
Procedural Review

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Root Cause Analysis

Common Tools / Analysis
Fishbone Diagrams
Pareto Charts, Run Charts, other Control Chart Methods
ANOVA and Design of Experiments
Causal Factor Charting
Root Cause Map

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Basic Points
Use 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 PARALYSIS
Analyze the likely causes FIRST
Use feedback loops to refine problem statement and causal
analysis
Most problems have more than one root cause
Dont 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 Statement
Begin the process with a simple statement of the problem.
Do not define the cause in the problem statement. Keep an open
mind.

Create / Gather Samples

Gather evidence showing the existence of the problem.
Product Returns
Collecting Documents
Creation of discrepant samples

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Problem
Identification
Sample Evaluation
Samples may be tissue products, packaging, test results, records, etc.
Product Review
Sample Dissection
Physical Testing
Chemical
Microbial
Physical
Functional

Records Review
Dates
Changes
Relationship to other relevant records
Chronology / History
Interviews
Duplicates in other locations
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Problem
Identification
Problem Statement Revision
Inspection / Testing / Review
Are results consistent with Initial Problem Statement?

Updated Problem Statement

Change Scope
Expand Scope
Reduce Scope

BE SPECIFIC based on observable data

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Identify Likely
Causes
Utilize Analysis Tools
Cause and Effect (Fishbone) Diagram
Causal Factor Chart
Process Flow Chart

Brainstorm
Do not rule out causes or assess likelihood
Look at all elements of the process
When in doubt start with 5 standard categories
Process
Environment
Materials
Human Factors
Equipment
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Cause / Effect
Diagram
Process
Lack of
Procedure
Detail
Writing Skills

Environment
Particulate

Valiation

Filters

Not
Calibrated

Doors
Humidity

No Procedure

Late

De-humidifier

Cleaning

Source Air

Temperature

No Procedure

Chemical

HVAC

Other Src.

Bag Seal
Failure

Wrong
Material
Supplier Error

Spec Error

Process

Mixup

Contamination
Environment

Cirriculum

Workload
Electrical
Supply

Maintenance

Overtime
Complexity

Wrong
Not Executed
Procedure

Storage

Operator

Installation
Air Pressure

Cleaning

Training

Design
Heating
Pressure
Element
Control

Wrong
Thickness

Setup
Environment

Operation

Reliability

Materials

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Controller
Failure

Distraction

Equipment

Human Factors

Hypothesis
Development / Testing
Causal Analysis
Identify 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 Development
Develop one or more scenarios to describe the failure based on the
failure investigation data and the causal analysis
Must be able to be evaluated / tested

Hypothesis Testing / Evaluation

Simple Inspection / Review of Data
Experimental Design
Worst Case Analysis
ANOVA
DOE
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Hypothesis
Development / Testing
Data Analysis
Appropriate Statistical Methods
Does the Data Support the Hypothesis?
Yes Continue to Corrective / Preventive Action
No Revise Hypothesis or Causal Analysis
Maybe Further Experimentation is necessary

Hypothesis Revision
Revise Causal Analysis based on Experimental Results
Revise Hypothesis Statement
Retest as Necessary

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Pareto Charts

92

100
90
80
70
60
50
40
30
20
10
0

44

Page 18

ne
Ju

M
ay

ril
Ap

ch
M
ar

br
ua
Fe

nu
Ja

ry

13

Month
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51

31

26

ar
y

Normalized Quantity

Calibration Errors

Control Chart

Hours

Average Production Hours

65
60
55
50
45
40
35
30
25

UCL

59
50 50

Mean

44

46 46

40 40 40 40 40

39 40 40

LCL

22

24

26

28

30

Week Number
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50

32

34

36

Misc. Charts

Temperature (C)

Bar Temperature by Position

236
235
234
233
232
231
230
229
228
227
226
0

2 3

8 9 10 11 12 13 14 15 16 17
Position

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Root Cause
Identification
Summarize Results of Hypothesis Evaluation
Identify all root causes that significantly contribute to failure
Identify significant interactions between root causes
Prioritize root causes based on impact
Develop 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 Table

Root
Cause ID

Description

Impact
(H/M/L)

Temperature Variation on Sealer Bar

Sealer Cycle Time

Material Thickness

Accuracy of Calibration

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Siginificant Interactions
Recommendations
Temperature variability increases
dramatically with decreased sealing
Replace sealer bar, increase calibration
cycle time
frequency, perform validation
Decreasing cycle time increases
temperature variation on sealer bar
Specify minimum cycle time as 30s in SOP
Lower end of current specification does
not seal correctly at highest temperature Revise specification, implement thickness
seen on sealer bar
measurement at RI
Revise instrumentation specifications for
use during sealer calibration. Improve
Calibration variation accounts for 20%
instrument accuracy to 1:10 ratio
of overall bar temperature variation

Documentation
Failure Analysis / Root Cause Analysis can be
included in:
Complaints / Adverse Reactions / HCT/P Deviations
Internal Deviations (Errors, Incidents, Accidents)
Validation Failures
Inspection Failures / Non-Conforming Product
Other Corrective / Preventive Action Projects

Key Elements of Documentation

Specific Problem Statement
Traceability / Tracking Information
Failures
Test Samples

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Documentation
Key Elements of Documentation (cont.)
Failure Investigation
Observational / Inspection Data
Test Information
Protocol
Data Analysis
Results
Conclusions

Causal Factor Identification

Hypothesis
Hypothesis Testing and Verification
Protocol
Data Analysis
Results
Conclusions

Root Cause Summary (report, table, etc.)

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Documentation
Points to Consider
How 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 Description
Traceability
Failure Investigation
Root 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 Description
Traceability
Failure Investigation
Root 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?

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