Non-Conformance Management

NonConformance Management
Stephen Fochios
SOLABS User Group Meeting
September 24th, 2013
Montreal, QC
What is a Nonconformance or “Deviation”?
The term “non-conformance” is synonymous with “Deviation”.
An NC is defined as: An Unplanned event, unexplained
discrepancy, or a departure from an approved instruction (i.e.
procedure, batch record, test method, specification, protocol).
Nonconformances can be discovered during audits, data review,
investigation, trend review, routine operations which can impact
product, facilities, equipment, data, systems, commercial or
clinical trials.
Nonconformance Types
2
Method
Manpower
Machinery
Materials
Environment
Who is Responsible for Reporting an NC?
EVERYONE!
If a nonconformance is observed, it is important
to report the event to Management as soon as it
is observed so the appropriate actions can be
initiated
What are the consequences of not reporting an NC?
Not reporting, or a delay in reporting an NC can severely
impact processes and result in an observation. If unsure, take
the conservative approach and report it anyways!
3
Regulatory Agencies
What Do Inspectors look for?
• A Quality Management System that covers all key areas: NCs, CAPA,
internal/external quality audit findings, training, complaints, supplier quality,
etc…
• Trends -were they properly identified, handled, and addressed.
• A Controlled Process that is in place and in use.
• Nonconformances are properly investigated and identify real Root
Cause
• Non-Conformances are closed within required timeframes
• CAPA corrects Root Cause and is closed effectively
• SISPQ (Strength, Identity, Safety, Purity and Quality) of the product is
properly assessed.
Can an Agency question me about an NC?
YES !!!
That’s why it’s important to make sure a thorough compliant
investigation is written!
Your signature is legally binding!
4
Determining if it’s a Nonconformance
- Example General Decision Tool
Question
1
Is the handling of the event covered by specific SOP ?
2
Do you immediately know there is no impact to :
•
Product
•
Material
•
Equipment
•
Area
YES
NO
Follow SOP
instructions
Proceed to
next Question
Proceed to next
Question
NC is Required
3
Can a further description clarify rather than correct the
original documentation?
Can be a
comment
NC is Required
4
For events at the time of performance:
Is this a correction to a GMP document that can be made
prior to the completion of the operation/process?
Can be a
comment
NC is Required
5
For events found AFTER the time of performance:
Can the required correction be verified from a GMP source?
Corrections must reference GMP documentation that
captures the same information.
• Clarifies the event- does not
correct it
• GMP source available to
clarify
• Easily explained, does not
require investigation
• Found at the time of
performance and corrected the
same day
Nonconformance
Can be a
comment
NC is Required
Suggestion: If it’s been determined that the event does not fit the
criteria of an NC, the operator will document an agreed upon
comment in the record where Management and QA will
initial/date.
5
Comment
• Deviation from procedure
• Repeat or recurring event
• Investigation required, immediate
root cause or product impact is
unknown
• Error can not be immediately
corrected
Classification
Determining the Level of Classification
Minor Nonconformance
• Low or No Risk of product impact to SISPQ (Safety, Identity, Strength, Purity, Quality
• No product impact is immediately known or requires minimal evaluation
• Probability of future detection is HIGH
• Controls and testing in place to detect this event
• No probability of impact to Quality of subsequent lots
Major Nonconformance
• Moderate Risk of product impact to SISPQ (Safety, Identity, Strength, Purity, Quality
• Product impact requires additional testing and is not immediately known
• Probability of future detection is MODERATE - HIGH
• Controls and testing in place to detect this event, however did not detect this event
• Low - Medium probability of impact to Quality of subsequent lots
Critical Nonconformance
6
• High Risk of product impact to SISPQ (Safety, Identity, Strength, Purity, Quality
• Product impact requires additional testing and is not immediately known
• Probability of future detection is LOW
• Controls and testing in place to detect this event, however did not detect this event
• High probability of impact to Quality of subsequent lots
Classification – Examples
• Medias or solutions incorrectly
prepared and discarded
• Minor labeling issues identified
during final product
labeling/inspection.
• Grammatical Errors that do not
impact critical labeling
information
• Correct samples collected but
documented on incorrect forms
• Wrong form used, but form
contains correct tests and
acceptance criteria
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• Outside Validated
Limits/conditions
• Trends
• Environmental Monitoring
• Temperature Excursions
• Testing Parameters exceeded
• Label Content Errors
• Post filter integrity test failure
• Use of rejected or expired raw
material
•Calibration OOT for equipment
used in the control or
measurement of critical
parameters
• Failure of Critical Quality
Systems
• Evidence of contamination of a
drug substance or drug product lot
•Failure identified through
periodic monitoring
• Aseptic processing media fill
failed acceptance criteria
• Breach of aseptic operation
conditions
• Validation failure of sterilization
or product impacting cleaning
process that has been used in
production lots
cGMP Compliance
Ensure you are properly trained on the SOP before executing the task.
DO NOT perform procedures from Memory
SOPs MUST be open when performing tasks (**FDA Observation**)
 If you do not understand STOP and ask for clarification.
 If an error occurs, STOP and escalate immediately to supervisor or designee for
guidance on how to proceed.
 Ensure that everything is documented at the time of performance!
“Not
Documented, Not Done!”
 Slow down, review your work for GDP before submitting for review.
 Focus on Right First Time!
 Be consistent with your work
Quality is Key- it’s about Quality not Quantity of work.
Always Be Compliant!
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Be Proactive!
Work Smarter not Harder!
Don’t Be Afraid To Speak Up If You
Have A Concern!
• Provide constructive feedback to peers with regard
to following procedures.
• Suggest Process improvements or more efficient
ways of operating.
Chances are if you don’t
understand it, your peers won’t
either!
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• Ensure the procedure is up to industry standards and
is properly reflecting the task you are performing
Catch problems BEFORE they occur!
GDP Requirements
Handwritten entries are in indelible ink (Black or Blue)
Pencil, gel ink, markers & RED pen are not accepted
 Empty spaces are "N/A” initial and dated
 “Ditto marks” or arrows are not acceptable
 The use of white out is strictly prohibited
 Entries must be clear, legible and made at the time of performance
 Correction to original documentation is one strike through and must
provide justification
Military time format (24-hour clock) is preferred however regular
time format is accepted
Acceptable date formats are properly documented
 Backdating is strictly prohibited
 When attaching a label to a GMP record, initial and date ensuring the
entry is overlapping both the label and document
 Do not record raw data on sticky notes, or loose paper as it is considered
original documentation
Always check your
work for GDP before
submitting it!
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Nonconformance
Expectations
11
• Check your work for errors and accuracy
• Be consistent with writing and reviewing
• If you don’t understand a reviewer’s comment, don’t
be afraid to ask!
• Address ALL comments
• Meet with approvers to ensure you understand their
expectations
• Keep your NC team informed and
involved…..Communicate!
• Write to the unknown audience (Think FDA
Inspectors)
• Be direct and to the point
• Keep it factual (No Opinions)
• Include only relevant information
• Project Manage your time and deadlines
Example Nonconformance Process Overview
Initiator
• Recognizes
potential NC and
informs
Management and
QA
• Performs
immediate
corrective
actions with QA
and Management
where possible
• Initiates NC
Owner
• Assumes
responsibility for
timely completion
of the NC
• Provides status
updates
• Identifies root
cause and suggests
CAPAs
• Approves the NC
as author
• Identify lots
associated
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Area
Management
• Assigns NC
owner
• Provides
resources and
ensures deadlines
are met
• Participates in
NC Team Process
• Reviews NC for
technical accuracy
QA
• Makes final
determination of
classification
• Ensures lot
tagging is
appropriately
assessed
• Reviews NC for
compliance and
accuracy
• Trending of NC
• Approves closure
of NC
SME
• Provides technical
support for root
cause and product
impact if required
• Provides
supporting memos
and reports if
required
Investigation
Scope: (example)
Scope: The scope of this event is limited to lot……. as
this was the only lot processed after the event which
occurred on (date). Subsequent batches are not affected
as a result of this discrepancy as… (explain why they are
not affected)
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• Details of all investigations and conclusions and
WHY it occurred
•Identify individuals involved by Title and
Department (minimum)
• Interviews• what day it was conducted?
• who you interviewed?
• what did they indicate?
• Background information
• Key decisions made
• Scope of investigation
• Review of historical data to identify related events
•All NonConformances should be investigated for
determination of root cause and product impact
•Major and Critical NCs require a more in depth
investigation
Root Cause Analysis
Identifying the Real Root Cause! Multiple Root Causes may exist!
STEP 1: Collect and Analyze Data
Minimum requirements
• Who?
• What ?
• Where?
• When?
• How Much/Many/Often?
STEP 2: Identify Potential Risk Factors
• Manpower
• Machine
• Materials
• Environment
Each needs to be justified why it was “Ruled In” or
“Ruled Out”
STEP 4: Determine if RC is Satisfactory:
Root cause is FACT based and corrective actions
will likely prevent this from reoccurring
STEP 3: Analyze Confirmed Potential
Factors:
Perform 5 Why analysis for each factor identified
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Interview Tips and Techniques
• Goal is to determine the true root cause(s)
• Ask for the opinion of those involved: what do they
think happened?
• Be open minded and non-judgmental
• Ask open ended questions when possible and don’t
guide their answers
• Ask what went right AND wrong
• Don’t overlook the obvious
• Be a good listener
• Ask them to re-enact the event
• Ask technical questions
• Use a friendly approach when interviewing
• Try to think of potential factors that may have
contributed to the event
• Ask how they think it can be improved?
15
Do NOT Place Blame
Interview Questions
Examples
• Do you recall any unusual
circumstances at the time of the event?
• Were you following the SOP?
• Do you find the SOP confusing? If so,
what can we do to improve it?
• Have you performed this procedure
before and do you feel comfortable
performing it?
• In your opinion, what do you think we
can do to improve the process to
prevent this from happening again?
16
What Questions do I ask?
Examples
• What do you think could have
contributed to this deviation?
• Why did you (overlook the error)?
• Were you distracted?
• What were you doing at the time of the
event?
• Who did you contact?
• What did you immediately do to stop
the problem?
Corrective and Preventative Actions - CAPA
Key Points to Consider
• CAPAs are created to correct the problem identified as the
Root Cause
• CAPAs should not continue the investigation
• Ensure your CAPA always aligns with your Root Cause
• Consult with QA to determine if a CAPA is already open before
initiating
• QA assigns the CAPA number once the NC is approved
• Assign Due Dates that are Realistic and Achievable
• When assigning the tasks, ensure the owner is aware and can
take on the responsibility
• If no CAPA is necessary, justification is required
Identifying the Correct Root Cause
will eliminate reoccurrence!
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Attachments
What Do I need to Attach?
• Anything directly referenced that can NOT be easily
retrievable from a published GMP system :
• GMP Systems: SOP or Report)
• GMP Systems but not retrievable: QC test
results, Chart Recorder or CMS results,
Calibration Certs, CoA, completed batch record
pages
• Memos originating to support NC must be
attached to show approval of memo thru NC
approval
• Attachments must include NC number,
attachment number, page numbers and initials and
date.
Providing Proof!
Examples of Attaching Proof
1)
2)
3)
Endotoxin testing results indicated they were within
specification (attach test results)
Product was quarantined (attach Inventory Control
sheet)
Unit was in alarm for 8 hours (attach alarm report)
No Emails!
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Approvals
When is Regulatory Affairs Approval Required?
• Missing Product
• Potential theft or adulterated product
• broken seals
• incorrect packaging
• boxes that appear compromised
• Impacted Product that has been released or is out of a company’s
control
• If it’s been identified as a possible reportable event
QA will help determine if Approval is
Required.
19
Status Update Example
NC Board- What is it?
•Tracks status of NC
• Dates routed for comments
• Dates comments were provided
• How many days it was with each approver
NC Meeting
• Status Updates
• Roadblocks/ New Developments
• Any New NC Events
• Attendees- Management,Initiator,Owner,QA
• Discuss classification
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“Where is my NC? Who has it?”
Standard Deviation Process
Standard Non-Conformance Process
Questions?
Stephen Fochios
Eliassen Group Life Sciences Consulting
sfochios@eliassen.com
1 (917) 297-9976