Professional Documents
Culture Documents
Failure Investigation Anselmo
Failure Investigation Anselmo
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
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
CONFIDENTIAL
Page 3
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.
CONFIDENTIAL
Page 4
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.
CONFIDENTIAL
Page 5
Process Overview
Key Process Steps
General Problem Identification
Gather / Create Samples
Failure Investigation and Experimentation
Examination / Dissection / Physical Testing
Hypothesis Development
Linking Analysis Data to Causal Factors
Hypothesis Testing
DOE / ANOVA / Simple Verification
Statistically Based Methodology
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
CONFIDENTIAL
Page 7
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
CONFIDENTIAL
Page 8
CONFIDENTIAL
Page 9
Basic Points
Use common sense
Use tools when they support a comprehensive analysis, not just because they
are available.
The problem dictates the tools, not the other way around
CONFIDENTIAL
Page 10
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.
CONFIDENTIAL
Page 11
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
CONFIDENTIAL
Page 12
Problem
Identification
Problem Statement Revision
Inspection / Testing / Review
Are results consistent with Initial Problem Statement?
CONFIDENTIAL
Page 13
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
CONFIDENTIAL
Page 14
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
CONFIDENTIAL
Page 15
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)
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
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
CONFIDENTIAL
Page 17
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
CONFIDENTIAL
51
31
26
ar
y
Normalized Quantity
Calibration Errors
Control Chart
Hours
UCL
59
50 50
Mean
44
46 46
40 40 40 40 40
39 40 40
LCL
22
24
26
28
30
Week Number
CONFIDENTIAL
Page 19
50
32
34
36
Misc. Charts
Temperature (C)
2 3
8 9 10 11 12 13 14 15 16 17
Position
CONFIDENTIAL
Page 20
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)
CONFIDENTIAL
Page 21
Root Cause
Summary Table
Description
Impact
(H/M/L)
Material Thickness
Accuracy of Calibration
CONFIDENTIAL
Page 22
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
CONFIDENTIAL
Page 23
Documentation
Key Elements of Documentation (cont.)
Failure Investigation
Observational / Inspection Data
Test Information
Protocol
Data Analysis
Results
Conclusions
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)
CONFIDENTIAL
Page 25
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
CONFIDENTIAL
Page 26
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?
CONFIDENTIAL
Page 27