Title: Deviation, OOS, Complaint Investigation_GMP_Dr. Amsavel
1Deviation, OOS Complaint Investigation and
CAPA
Dr. A. Amsavel, M.Sc., B.Ed., Ph.D.
2OVERVIEW
- Definition
- Requirement
- Deviation, OOS and reporting
- Investigation
- RCA
- Investigative tools Why Why , Cause Effect
and FTA - Human error
- CAPA
- Implementation
- Investigation report
- Verification for effectiveness
3DEFINITION
- Correction An action to eliminate a detected
nonconformity. Remedial action
Repair, rework, or adjustment - Corrective Action The action taken to eliminate
the causes of an existing nonconformity, defect
or other undesirable situation in order to
prevent recurrence. - Preventive Action The action taken to eliminate
the cause of a potential nonconformity, defect,
or other undesirable situation in order to
prevent occurrence. - Nonconformity non-fulfillment of a specified
requirement. Any material or process that
does not meet its required specifications or
documented procedure. - Note There is no definition for CAPA in the drug
cGMP regulation
4ROOT CAUSE
- Root Cause identification is the most important
step - Root Cause Analysis (RCA) is a systematic
approach to identify the actual root causes of a
problem. - CAPA will be effective to eliminate the
reoccurrence if root cause is identified
correctly and accurately
521CFR Requirement( As per Medical device)
- 21 CFR 820.100(a) Regulatory Requirement -
Establish and maintain procedures for
implementing corrective and preventive action - 21 CFR 820.100(a)(2) Investigate to Determine
Root CauseInvestigate the cause of
nonconformities relating to product, processes,
and the quality system - 21 CFR 820.100(a)(3) Identify Corrective and
Preventive ActionsIdentify the action(s) needed
to correct and prevent recurrence of
nonconforming product and other quality problems - 21 CFR 820.100(a)(4) Verify/Validate Corrective
Preventive ActionsVerify or validate the
corrective and preventive action to ensure that
such action is effective and does not adversely
affect the finisheddevice
6Preamble
- There are several investigation tools for
deviation / OOS/ complaint investigations - Use effective tool to identify the root cause
usually with the use of a single tool. - Complex investigations may require two or more
different tools - Familiar tools used widely are
- WHY -WHY analysis
- Fish Bone Analysis
7Investigation Tools
- RCA Technique/ Methodology
- Why- Why analysis
- Brain storming
- Cause and Effect / Ishikawa / Fishbone Diagram
- Fault Tree Analysis (FTA)
- FEMA etc
8Want to solve the problem !Think Differently
We can not Solve our problems with the same
thinking we used when we created them -Einstein
9How to Report Deviation OOS
- Description Describe clearly the
Problem/Failure. - Determine What, Why, Where, When, Who, How?
- Immediate Actions taken Contain/ stop continue
- Immediate ( known ) Product Quality Impact
- Complete the above within 24 hours from time of
an incident identified - Initial ( preliminary ) QA Review
- Above section must be completed within 2 days of
receipt - Complete the investigation as per SOP (preferably
3-5 days)
10Investigation
- Objective Prevent the similar failure by
effective CAPA. - Seven steps of CAPA
- Identification Clearly define the problem
- Evaluation Appraise the magnitude and impact
- Investigation Make a plan to research the
problem - Analysis /RCA Perform a thorough assessment
- Action Plan CAPA -Create a list of required
tasks - Implementation Execute the action plan
- Follow Up Verify the effectiveness
- Do not release the deviation /OOS batch.
until establish the conclusion
11Deviation/Incident Reporting
- State the incident Clearly /measurable terms
- What, When, where, how often, how much,
- Emphasize the quality risk,
- safety, death, injury, rework, etc.
- Do not write incident as
- negative descriptors, inflammatory statements
- words that are broad and do not describe the
conditions or behaviour such as careless,
complacency, neglect, oversight etc
12Deviation/Incident Reporting
- If An Incident /problem is well defined , a
problem half solved - Keep in mind it is to Correct, Prevent
Improve - No shortcut to conclude as human error
- 5W
- What is affected
- Where does the problem takes place
- When is the problem indentified
- Who is indentified
- What is the consequence
- 2H
- How much is affected
- How often has the problem occurred
13Investigation Process
- Review past history /similar issue
- Review records and documents
- Review process/operations
- Review the situation/ environment
- Interview people closest to the problem
- Inspect and test the product/ material
- Gemba-Inspect equipment facilities at site
14Investigation Steps
- Information must be captured from the people who
were involved - Gather the facts quickly to avoid the loos of
information/ evidence - Determine what historical data is available
- Determine what is known rather than what is from
memory
15Investigation Report
- Record the details
- Location
- Date and time of occurrence, discovery
- Personnel ( titles / names ) involved
- Explain why the event is different from what is
expected - Initial scope
- Product / materials
- Lot/batch / campaign
- Equipment / train
16Review of Documents
- Review of BPR
- Review of Test data/records
- Review of situation surround of an incident
- Review of Systems / facility/ Equipment
- Eg. Environment, Log book, cleaning, handling
- Verify any such past incidence report
- Any additional testing required
17Root Cause Analysis (RCA)
- Root cause and the weed
- Weeds can be difficult to remove once they start
to grow and spread. - To eradicate the weed you have to get below the
surface, identify the root, and pluck it out. - Thus, you have to go beyond the obvious,
ascertain an accurate route cause, so the
appropriate corrective action can be pursued to
prevent recurrence.
18Root Cause Analysis (RCA)
- A root cause is a system or a process that
caused the problem you observed. - Root Cause That condition, action, or lack of
actionthat led to the problem occurring. - Root Cause Analysis The process of identifying
all the causes (root causes and contributing
causes) that have or may have led to an
deviation.
19Possible Reasons for Failure
- Human Error
- Equipment Failure
- Procedure is Inadequate or Not Clear
- Procedure not Followed
- Training Inadequate
- Design Error
- Poor Communication
20What are Human Errors?
- A mistake made by a person rather than a machine
that produces a result that is Undesirable - The organization does everything to prevent the
problem. - However, the employee ( operator/ peer/
supervisor/ management ) still make a mistake - Everyone can make error no matter how well
trained and motivated -
21Human Error or Violation?
- Two types of human failure Errors and
violations. - Identify them correctly and to be addressed
appropriately - A laboratory technician performing two tests
simultaneously , but used the wrong sample for
one of the tests - A production operator filled out a cleaning
record without performing the task - A violation is a deliberate deviation from a rule
or procedure. - What influences to Error or Violation
- Eg Time pressure, design of controls,
procedures, training and experience, fatigue, and
levels of supervision etc.
22Human errors occur due to
A bad systemwill beat a goodperson every
time -W. Edwards Deming
- Inattention
- Memory lapse
- Failure to communicate
- Exhaustion /poor working conditions
- Ignorance
- A number of other personal and environmental
factors - Poorly designed equipment / facility.
- Eg Temperature gauge is fixed at roof or
operation in ground floor , values fixed at first
floor
23Human Error
- Human errors are not root causes
- Human errors are symptoms or consequences of
deeper causes - Develop error-tolerant systems to prevent errors
- Design of the job, equipment, procedures, and
training. - Change the People
- Without Changing the System and
- the Problems Continue.
- -Don Norman
24Human Error Type
Error Type Definition
Inadequate process Process does not achieve correct outcome
Incorrect procedure Procedure does not reflect the process
Lapsed/ no training Training/competency assessment out of date, not completed
Inadequate training Training/competency assessment does not cover error made
Ineffective training Training is adequate, but misunderstood
Procedural steps Procedural steps missed out (Intentional omitted or forgotten)
Concentration maybe due to rushing Steps in the process have been completed, but not accurately
25- You Cant Solve A Problem Until You Are Asking
- The Right Question
265 Why analysis- Sakichi Toyoda
- A simplistic approach exhausting the question
Why? - It is like FTA and brain storming
- Preferred for investigations of specific
deviations as opposed to chronic problems. - Asks why events occurred or conditions existed
iterative questioning - Drills down to the root cause
- By repeatedly asking the question Why?, until
symptoms and identify the Root Cause of the
problem. - Each Why bring Obvious Excuses
Reasons Causes Root causes
27Disadvantages of 5 Why Analysis
- This time consuming brainstorming process may be
tedious for team members trying to reach
consensus. - Results are not reproducible or consistent.
Another team analyzing the same issue may reach a
different solution. - Some time Root causes may not be identified.
28Kepner Treqoe Matrix ( Questions)
29Cause and Effect /Fishbone Diagram
- It is also called as Ishikawa Diagram
- Establish a team which possess knowledge on this
- Write the Problem Statement at Head of a Fish
bone. - 6M or 5ME As Main Branch Manpower, Machines,
Materials, Methods, Measures, Milieu /
Environment. - Identify the main categories of possible causes
- Add the sub-branch/factors in the diagram until
to get useful information. - Place these at ends of branches emanating from
the back bone.
30Cause and Effect /Fishbone Diagram
- Brainstorm all possible causes and place these in
the suitable area of the diagram. - Use checklist /questions to support brainstorming
- Do not discourage the members ideas
- Analyze the results of the fishbone after
obtained adequate detail to identify most likely
causes. - List most likely causes in priority order. First
item being the cause or most probable cause. - Typical Fishbone diagram....
31Typical Fishbone Diagram
32Example of Fish Bone Questions
- Measurement
- Is process performed as per established
parameters? - Are all measurement /entries / data correct?
- Calculations correct and verified?
- Are measuring devices appropriate, qualified
calibrated? - Do previous inspection or maintenance results
indicate potential problems? - Is quantity of input and output correct. Is
quality suitable - Is there any previous atypical results or
trending history ie OOT - Recent documentation history?
33Example of Fish Bone Questions
- Method / Process
- Is the process validated?
- Is the process operating within its validated
parameters? - Any deviations from standard operating
procedures? - Is the right procedure used?
- Is the procedure accurate / clear?
- Samples pulled at appropriate steps?
- Any sampling issues?
- Were processing steps properly verified?
34Example of Fish Bone Questions
- Machine/Equipment
- Has equipment been recently replaced or repaired?
- Is qualified and suitable assessed
- It is within calibration?
- Is preventative maintenance completed?
- Maintenance records reviewed?
- Are any equipment cleanliness issues?
- Equipment capacity or availability an issue?
- Is equipment being used for its intended purpose?
35Example of Fish Bone Questions
- Materials
- Are material / components tested approved ?
- Is properly released and issued ?
- Are materials charged correct quantity in
sequence? - Material properly stored temperature /
humidity? - Is within expiration dating?
- Is properly labeled segregated adequately?
- Is it from new source / vendor?
- Material sensitive/ protected
36Example of Fish Bone Questions
- Environment
- Is any environmental condition that contributed
to failure? - Is temperature maintained in the area and
product ? - Is equipment / room properly cleaned?
- Is cleaning validated?
- Cleaning agent /sanitization solutions used is
appropriate ? - Check the conditions Air Flow, Pressure,
Temperature, RH - Is any other activity performed at the same time
that could contributed - Is personnel monitored and maintained within
limits
37Example of Fish Bone Questions
- People /Men
- Are personnel properly trained in the procedures?
- Are the operators familiar with the activity?
- Are adequate number of personnel worked in the
particular procedure? - Verify break/ shift change or any other issue
- Is adequate oversight of operators possible?
- Are procedures available to operators conducting
the activity?
38Fault Tree Analysis
- FTA can be used to investigate complaints,
deviations, unusual events - It is a kind of deductive procedure used to
determine failures and human errors that could
cause Failure/ undesired events - Approach to failure of the functionality of a
product or a process. - FTA is pictorial presentation of the fault modes
based on logical reasoning - FTA build by probable causes to identify
potential causes of system failure before actual
failure occur. - Conclusion after completing an FTA.
39Fault Tree Analysis Steps
- Define the fault condition and write down the top
level failure. - Using technical information and professional
judgments, determine the possible reasons for the
failure to occur and write down below the failure
in the tree.. - Continue to break down each element with
additional gates to lower levels. - Consider the relationships between the elements
to help you decide whether to use an "and" or an
"or" logic gate. - Finalize and review the complete diagram. The
chain can only be terminated in a basic fault
human, hardware or software. - If possible, evaluate the probability of
occurrence at each elements
40Typical Fault Tree Analysis Diagram
41Fault Tree Analysis Diagram
42Rules followed for FTA
- FTA shall focus on the decision of experts from
various disciplines and provides common outlook
for the problem. - Agreements and differences in opinion on the
inputs and importance are considered in FTA. - Members has to be encouraged, not likely to feel
threatened. - FTA shall focus on how the system operates, not
personnel. - Graphic shall Identify the possible causes of
failure. -
-
43Avoid during Investigation
- Do not focus Who made a mistake? Focus on
Why did this go wrong? - To avoid reaching erroneous / incomplete
conclusions in the rush state. - Scope and extent of failure is not understood
fully - Being superficial ( at symptom level ) and not
reaching the depth ( at root cause level ). - Lack of timely conclusion leading to improper
product realisation. - Thus failure is subsequently repeated.
44OOS Reporting Investigation
- Description clearly state the problem
- Phase1 Check list Chemist supervisor
- Hypothesis test
- Retest
- Investigation
- Laboratory / Manufacturing
- RCA investigation tool / methodology
- Fishbone diagram- men/ method/material/machine
- Process details/ analysis detail
- CFT QA, QC, Production Technical service,
Engineering , RD etc - Identify Other Batches Potentially Affected
- Justify Selection Consider distributed lots
if any - Conclusion
- Documentation
45Evaluation of product Impact
- Evaluate Product Impact / Disposition
- Additional testing / results
- Provide reason for accept / rejection of the
batch - Justify the exclusion of other batch if required
- Consider toxicological evaluation if required
- Reprocess/ reworking
- Stability
46Investigation Document Review
- Review all documents and records of the
manufacturing process. - A written record of the review includes
- A clear statement of the reason
- Summary of manufacturing process aspects that
could cause the problem - Results of documentation review with probable
cause. - Results of previous reviews
- Description of corrective actions to be taken.
47Resolution
- Typical Resolutions to Causes
- ? Procedural changes / updates
- ? Process Changes
- ? Engineering changes
- ? Process validation
- ? New training programs
- Typical Resolutions to Symptoms
- ? Fix it /Re-work / Correct
- ? Re-Training
- ? Disciplinary action
48Conclusion of Investigation
- If a cause is found, invalidate the initial
result and use the retest value(s) in its place. - If the OOS is confirmed the batch is rejected.
- If the OOS is inconclusive and the retests are
within specification, then QA may be able to
justify releasing the batch.
49 Contents of Investigation Report
- Reason for the Investigation
- What event or finding initiated the
investigation - How and when Identified
- Evaluation
- Consider related activities and impact (immediate
overall) - Describe What Happened
- When
- Where
- What immediate actions were taken
50CAPA
- Identify Corrective Actions
- Resist operator error corrected with retraining
- May include additional monitoring / assessment
- Implementation must be timely
- Identify Preventive Actions
- Success depends on adequate identification of
root cause - Interim solution may include additional
monitoring
51Effectiveness Verification of CAPA
- After implementation of CAPA effectiveness has
to be verified - Check that proper controls are established
- Verify the proposed training / communications
- Verify that CAPA show the improvement and there
is no such problem reoccurs - Verify that all the recommended changes are
implemented and documented - Verify that implemented CAPA, is not have any
other adverse impact - Document the effectiveness verification
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