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Human Error, Root Cause Analysis and Conducting Objective and Effective Investigations


Title: CAPA, Investigations and Quality Systems Author: Karen Ginsbury Last modified by: Karen Ginsbury Created Date: 5/8/2008 6:55:27 PM Document presentation format – PowerPoint PPT presentation

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Title: Human Error, Root Cause Analysis and Conducting Objective and Effective Investigations

Human Error, Root Cause Analysis and Conducting
Objective and Effective Investigations
  • Presented by Karen GinsburyFor IFF Denmark
  • November 2012

Workshop Objective
  • To understand why operators make mistakes and how
    to identify the real problem rather than human
    error retrain corrective actions

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What is an investigation?
  • You are not investigating if whenlooking for
    EVIDENCE you start outBELIEVING you know
  • EVIDENCE provides proof
  • Proof is convincing objective evidence that
    compels the mind to accept a truth or fact

MHRA April 2011 March 2012
  • 303 inspections 26 criticals 644 majors
  • Top 10

EU GMPs Part 1Finished Product
Chapter 1 - PQS
  • Under Quality Assurance

US GMP Trends Risk Management
Suicide or Murder?Ill never find the killer
Sudoku its impossible
  • How many of you completed the puzzle
  • How many of you have done a Sudoku in the past?
  • Here is a fiendish puzzleSee if you can finish
    it by the end of the day. You can ask anyone
    else or do it in a group AFTER you have spent 30
    minutes trying to do it yourself (NOT during the
    class take it home if necessary)

The Orange Juice Problem and Lateral Thinking
How can you move one glass only and have
alternating filled / empty glasses?
Impossible? You tell me.Logical / Rationale
  • There are three boxes, one contains only apples,
    one contains only oranges, and one contains both
    apples and oranges. The boxes have been
    incorrectly labeled such that no label identifies
    the actual contents of the box it labels. Opening
    just one box, and without looking in the box, you
    take out one piece of fruit. By looking at the
    fruit, how can you immediately label all of the
    boxes correctly?

Course Objective Take Home
  • Understand how to
  • Effectively and objectively investigate
  • Deviations, Non-conformities, Unexpected,
    Unwanted, Undesirable, OOS, Out of trend
  • events and document the investigation
  • Concisely
  • precisely

Expanding vs Focusing Thinking
????? ?????? ?????? ????? Identify Problem Expand
??????? ?????? ????? ??????? Problem well defined Focus
????? ?????? ??????? ?????? ???? ?? ?? ?????? ????? ???????? Analyze causes Expand
??????? ?"? ????? ?????? ????? ??????? Analyze causes Focus
???? ?????? ????? ?????? ?????? Root cause identified Focus
????? ?????? ????? ?... Root cause identified Expand
????? ??????? ??????? Generate solutions Expand
????? ??????? ?????? ????? Solution chosen Focus
Cool Neutral, Information needed Looking for
Emotive Gut feelings Intuition Hunches
Critic Analyst Logical Negative
Sunshine Optimist Logical Positive
  • Six Thinking Hats

Creative Growth Possibilities Ideas
Cool Agenda Process Organizer Overview
Bioburden IPC for aseptic fill product before
  • Too Numerous To Count / ml
  • Specification NMT 10 cfu / ml
  • Alert level (historical data) NMT 4 cfu / ml
  • Off the top of your head what do you think is the

Karens questions
  1. TNTC / ml too numerous to counta very
    different result to those normally obtained if
    the alert is 4 cfu / ml
  2. Any other samples TNTC for this or other products
    in the past months - answered in the
    investigation checklist BUT not analyzed and no
    conclusions in report
  3. (Has anything changed in the sampling plan? Is
    the same lot of containers being used? What
    about different starting materials?)
  4. Who took / tested the sample?
  5. Was EM performed?
  6. Where was the test performed? What was tested
    immediately before this product? What
    disinfectant is used for the BSC? Do the
    cleaning records show that the BSC was indeed
    disinfected? Who did that? When were they last
    observed doing it?
  7. What was the ID and where is the colony
    morphology of the plate documented? Was there a
    single colony type? Is there a picture of the
    plate? How was ID performed? Is the organism in
    the library etc. etc. etc.

The Investigation
  • Test Procedure
  • Two 15ml portions were filtered and washed with
    PW and PWTL and filters were transferred to TSA
    and SDA
  • Another 1ml portion was filtered and washed with
    PW only and then the filter transferred to TSA
  • TSA incubated 30 35 2 days. SDA 20 25 5
  • For exact sample testing see method ID43253 ver
    02, attachment 2

This is the most important part it is the
analyst interview Did the 15ml sample show an
identical pattern to the 1ml plate? Same
contamination single strain or more than one
microbe? After the same incubation time? Why is
the procedure different for the 1ml sample (PW
only and not PWTL) and only TSA?
More Details
TSA plates tested for GPT well they would be
valid they showed TNTC so are only interested
in STERILITY was this part of the control
testing? What does vastly mean MUST give
figures how many plates were received and how
many used in tests? Did the tests show zero
counts or low counts where zero is usually
Experienced Operator
More Details
  • Historical results show no or very low microbial
    bioburden counts for this product
  • Contamination is Micrococcus Luteus

Historical results from when to when? Was
Micrococcus luteus the ONLY bacterium seen on the
TNTC plate Is there a photo of the plate Is there
a morphological description of the contamination
documented? Next piece of information says BET
lt0.005 EU/ml so what M. luteus isnt an
endotoxin producer! Can give the information but
draw the appropriate conclusion
A Few Minutes of GMPs
  • The GMP regulations
  • EU and US on handling deviations
  • Q10 Pharmaceutical Quality Systemand CAPA

The GMP RegulationsEuropean Directive
  • 1.3 (vi) any significant deviations are fully
    recorded and investigated
  • 5.15 Any deviation from instructions or
    procedures should be avoided as far as possible
  • 5.39 Any significant deviation from the expected
    yield should be recorded and investigated

21 cfr 211.100
  • Written procedures deviations
  • (b) Written procedures and process control
    procedures shall be followed in the execution of
    the various production and process control
    functions Any deviations from the written
    procedures shall be recorded and justified

  • A pharmaceutical company should have a system for
    implementing corrective actions and preventive
    actions resulting from investigation of product
    quality feedback and trends from process
    performance and product quality monitoring

  • A structured approach to the investigation
    process should be used with the objective of
    determining root cause
  • The level of effort and formality of the
    investigation should be commensurate with the
    level of risk
  • CAPA methodology should result in product and
    process improvements and enhanced product and
    process understanding

Application Across the Product Lifecycle do I
need to investigate?
  • Always covered in inspections
  • The display window of the firm
  • Reporting culture
  • Level of understanding
  • Level of efforts invested
  • Level of documentation skills
  • A sole effort of QA?
  • Do they lead to continuous improvement?

  • Last year we had less deviations than
  • In a deviation categorized as MAJOR, QA decided
    not to conduct an investigation
  • Same effort invested in trivial and major
  • Majority of root cause defined as human error
    and retraining is chosen as the sole corrective
  • Deviations are not closed in a timely manner and
    the statistics looks bad

  • Environmental monitoring deviations starts and
    ends with ID of the microorganism
  • Recurrent deviations with copy paste
  • Immediate cause for deviations (e.g. electrical
    blackout) is defined as root cause
  • Conclusion are drawn based on RD scientists
    statement the product is known to be stable at
    this temperaturewith no supporting scientific

  • Failure in systems (e.g., HVAC) not correlated
    with production activities in the affected area
  • Written documentation does not allow
    understanding of what happened and lengthy verbal
    explanations are required
  • Shallow investigations if at all following
    calibration failures
  • Investigation only at the level of the impact on
    the product

  • Trends revealed in PQRs or System/Equipment QR
    not investigated
  • Internal e-mail correspondence presented as an
  • Majority of CAPA activities as response to
    failures preventive actions based on proactive
    activities such as risk assessments or internal
    audits are rare

Circumstantial Evidence
  • is a very tricky thing answered Holmes
    thoughtfullyit may seem to point very straight
    to one thing but if you shift your own point of
    view a little, you may find it pointing in an
    equally uncompromising manner to something
    entirely different

Obvious facts
  • there is nothing more deceptive than an obvious
    fact, he answered laughing
  • besides, we may chance to hit upon some other
    obvious facts which may have been by no means
    obvious to Mr Lestrade.
  • I shall approach this case from the point of
    view that what this young man says is true, and
    see where that hypothesis leads us.

and finallylook for the flawChallenge the
  • you have read the evidence. You have formed
    some conclusion? Do you not see some loophole,
    some flaw? Do you not think that he is innocent?

Capturing the Event
  • Description of the Deviation
  • Four case studies will be distributed work with
    your colleagues and come up with a list of
    questions regarding additional information you
    need in order to understand the nature of the

Fishbone Diagram - Cause and Effect
  • ????? ????? ?? ?????? ?????
  • ??? - Who?
  • ??? - What?
  • ????? - where?
  • ???? - when?
  • ???? - why?
  • ????? - how?

miscellaneous / management
Possible Causes
  • You are going to Brainstorm but because we are
    not good at doing that lets warm up first

Problem statementThere is a mouse in the cheese
  • A large block of very good Swiss cheese on a
    kitchen table a few feet away from an open screen
    door. The weather outside is warm. A man comes to
    the table for some wine and cheese and sees a
    mouse in the cheese
  • Comments, questions, hypothesesregarding
    contributing causes andmost probable
    cause(s)Please work on your ownwrite it
    downand think laterallythere are NO WRONG
    ANSWERS at this stage

Comments, Hypotheses
Mouse in Cheese
  • Here is a solution to the problem
  • Throw out the cheese with the mouse and open up a
    new packet of cheese
  • Have I solved the problem Yes / No?
  • Defend your answer

Mouse in Cheese 6MsFishbone
  • Man Group 1
  • Machines
  • Materials Group 2
  • Methods
  • Measurement Group 3
  • Miscellaneous / Mother Nature / Management
  • Please work in groups be a bit crazywrite it
    down at least three for each category - we need
    ideasthere are NO WRONG ANSWERS at this stage

A Tool
  • Root Cause Analysis is a tool for identifying
    prevention strategies. It is a process that is
    part of the effort to build a culture of doing
    things right, continuous improvement and move
    beyond the culture of blame

Root Cause Methodology
  • NOT intended to identify a single cause
  • Look for
  • Contributing cause(s)
  • Most probable cause(s)

The Problem Solving Cycle
There are ALWAYS at least several hypotheses for
any event
I can think of at least 7 different
explanationsnow I am going to look for facts
Cool neutral, information needed looking for
Emotive gut feelings intuition hunches
Expand Thinking Using
  • Process Flow chart from test method and SOPs
  • Fishbone / Ishikawa 6ms MANY possible causes
  • Relates cause and effect
  • Sorts ideas
  • Why- why diagram

Focusing Thinking
  • Data collection and analysis tools
  • Control charts
  • Graphs
  • Histogram
  • Pareto chart
  • Process capability
  • Run chart
  • Survey

You have started to collect data but is it
sufficiently organized and are you drawing
OBJECTIVE conclusions?
There is a mouse in the cheese5 whys
There is a mouse in the cheese
  • Alternative solutions
  • "Be sure to close screen door
  • "Put a note on door asking, 'Did you latch me?
  • Comments please

Mouse in the Cheese
  • Should the cheese be left on the table?
  • Why was it left on the table?
  • If it is left on the table shouldnt it be
  • Why wasnt it covered?
  • Did the mouse definitely come from outside?
  • Should there be a pest control program

Jurans Universal Sequence for Making Quality
  • Study the symptoms of the defects and failures
  • Theorize as to the causes of these symptoms
  • Test the theories until the cause(s) is known
  • Stimulate remedial action by the appropriate

Use Project Teams A Project is a Problem
Scheduled for Solution CAPA
Root Cause Analysis
  • The goal of a Root Cause Analysis is to find out
  • what happened
  • why did it happen
  • What is the risk to product through
    understanding cause(s) of the event rather than
    just symptoms
  • what do you do to prevent it from happening

Lets take the case studies and Hypothesize
  • What could be the reasons for the event

Case 1
Case 2
Case 3
Case 4
Now select some most probable and contributing
causes for case study 1
Now do 5 whys for the most probable causes
Now suggest some corrective actions
Completing the Cycle
  • A whole is that which has beginning, middle and
    end, Aristotle, Rhetoric
  • To complete a deviation / change report
  • all relevant details documented
  • complete investigation recorded
  • final product disposition verified as implemented
  • corrective actions / tests verified as
    successfully performed

Deviation Documentation
  • Lets Write a Deviation Report as we think it
    should look for one of the cases we studied today

MHRA UK Regulator
  • Paul Hargreaves emphasised that the MHRA, and
    other regulatory agencies, expect companies to
    actively reduce the frequency and severity of
    human error
  • Regulatory agencies expect companies to actively
    prevent errors from happening, not to react after
    the event

MHRA UK Regulator
  • The root cause of a vast majority of quality
    problems is not human error. Such a conclusion
    is usually symptomatic of a poor and inadequate
    investigation. Most informed regulatory auditors
    will refuse to accept retraining as a suitable
    corrective action

MHRA UK RegulatorError Reduction Practical
Tools and Techniques
  • Achieving a genuinely open and blame free working
  • Taking a positive approach to mistakes and error
  • Driving out complexity
  • The importance of User Centred Design (UCD)
  • The crucial importance of SYSTEM SAFEGUARDS
  • Avoid overly complex quality management systems
    which can cause errors

Categorize and Accurately Report Error
Learning Gap
  • Dont know what to do
  • Missing skill
  • Missing knowledge
  • Failure to understand the consequences
  • Lack of risk communication

Memory Gap
  • know but dont remember at the time of
    performing an actionor
  • Unable to apply the skill at the time of
  • Unable to apply the skill in a particular

Omission Errors
  • Failure to document a step in a procedure
  • Generally arises because of poor documents user
    friendly documents encourage accurate recording
  • Skip a step in a procedure e.g. because of an
    interruption or lack of concentration (or perform
    same step twice)
  • Use wrong reagent / wrong type of water

Inconsistent Performance
  • Know and Understand but variability in method
    / standard leads to inconsistent results e.g.
  • Poor instrument maintenance
  • Unclean instruments / contaminated incubator
  • Poor reagent control e.g. contaminated LAL
  • Unclear method leads to inconsistent performance
    between different or even the same analyst
  • Analysts mood / tired / angry / bored / stressed
    / over-worked too many tests per analyst

  • know but apply technique wrongly or use the
    information incorrectly
  • Transcription errors
  • Touch tip to sample and then use for a new sample
  • Scratch face before opening reagent
  • Failure to disinfect BSC

Decision Errors
  • Wrong decision made
  • In a particular situationor
  • Given a series of facts / information
  • E.g. put plates back in incubator rather than
    report breakage
  • analyst error when results may be true

MHRA UK RegulatorActively REDUCE and REMOVE
Risk Increasing Factors
  •  Can conduct audits to identify RIFs
  • Structural (poor lighting, material and people
    flows etc)
  • Organisational (poor communication, leadership
    and complex, hierarchical bureaucracies)
  • Process related (poor documentation / process
  • Poor work place ergonomics
  • Individual (fatigue, stress, competence, skill

  • After an event conduct an audit for RIFs
  • Observe several analysts performing the operation
    and ask why? why? why?
  • Why did the plates drop
  • was the incubator overcrowded?
  • Was there no trolley nearby?
  • Was there no workspace available?
  • Was the operator rushed / stressed?

Juran inadvertent error
  • Inadvertent errors come from workers inability
    to maintain attention
  • The errors are unintentional, unwitting, and
    unpredictable (they exhibit randomness)
  • The bulk of remedies lie in fool-proofing the

Juran Technique Errors
  • Technique errors arise because the worker lacks
    some essential technique, skill, or knowledge
    needed to prevent the error from happening
  • They are typically unintentional, specific,
    consistent, and unavoidable
  • Remedies often require the discovery (using the
    diagnostic techniques) of differences of
    technique which represent the beneficial knack
    that produces superior results
  • and training others or changing the process to
    embody the better method

Inadvertent and Technique Errors
  • Usually workers cannot find the reasons for
    defects themselves, and therefore they will keep
    on doing what they have been doing
  • They will keep on producing defects
  • This will go on until they get the help they need
    from management

And regarding operator error
  • Juran on operator error Management has the
    responsibility to provide a
  • 1. Means for knowing what he is supposed to do
  • 2. Means for knowing whether he is doing what he
    is supposed to do
  • 3. Means for changing what he is doing if it does
    not conform with what he is supposed to do

In Conclusion
  • Expand your thinking1 question three or more
    possible explanations for every deviation event
    write down at least three each time and be sure
    to include I / my department messed up
  • Collect data and analyze to convert into
  • Apply the information as knowledge to draw a
    scientifically defendable conclusion

Thank You for your AttentionAny questions
  • Find us at

But not all the answersKeep an open mind
  • Some answers from earlier on

Documenting the Deviation
  • What was missing in the report
  • When (did it occur)
  • Who (discovered it)
  • How and When (did they discover it)
  • Whom (did they notify)
  • When (did they make the notification)
  • What (immediate action was taken)
  • What was the scale of the deviation e.g. whole
    batch affected, portion of the batch segregated
    how far out of specification (give the spec)

Which are Contributing vs Most Probable?For
the cheese
  • cheese left on the table why? E.g. refrigerator
    broken / man lazy CONTRIBUTING
  • If it is left on the table shouldnt it be
    covered? Why wasnt it covered? No cover
    available / man lazy CONTRIBUTING
  • Did the mouse definitely come from
    outside?Should there be a pest control program
    depends if the mouse is the kids then that
    could be the most probable cause if not then
    contributing cause
  • Screen door open? most probable causeAutomatic
    latch / get rid of cat?
  • What will happen if you get rid of cat??????Be
    careful not to be too quick to chose a corrective
    action plan without examining potential
    consequences and collecting more data to support
    your hypothesis