Investigation of Deviation
Investigation of Deviation
PROCESS IN
DEVIATION
MANAGEMENT
SAMSON FATOKI
(MPH, FPCPharm)
Assistant Director
DER, NAFDAC 1
OBJECTIVES
• To explain the meaning and importance of
Deviation management in GMP
• To highlight regulatory requirements for
deviations
• To enhance compliance to GMP requirements
and entrench the culture of continuous
improvement
2
INTRODUCTION
• Deviation management plays a key role in
assuring quality in products by
contributing to continuous improvement
• It is an essential element of a well
established Quality Management System
(QMS)
• Deviation management has become a
requirement of cGMP
3
REGULATORY REQUIREMENTS
NAFDAC GMP GUIDELINES FOR PHARM.
PRODUCTS 2016
REGULATORY REQUIREMENTS (Cont’d)
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• Sections 1.5, 2.1, 9.14, of WHO TRS 986 Annex 2 and sections
15.27, 16.3, 17.3 of WHO TRS 961 Annex 3 mentions relevant
requirement for deviations
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What is Deviation
• There is no definition of “Deviation“ in the GMP guides of
WHO, PIC/S, EU or US. • Use of different terminologies such as
– deviation, discrepancy, atypical situation, non- conformity
9
WHAT IS DEVIATION
• Any non compliance of established GMP
standards or of approved requirements
specifications and standard operating procedure.
It should be documented, evaluated and when
appropriate investigated in order to determine
the originating cause (s) to prevent recurrence
• Simply put it is a departure from approved
procedure, instruction or established standard.
• It can also be defined as “Failure to meet critical
limit”
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WHAT IS DEVIATION
(CONT’D)
• For compliance to GMP and for the sake of continual
improvement, deviations are recorded in the Deviation Report
(or other similar name)
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WHAT IS DEVIATION
(CONT’D)
• It is expected that manufacturers will establish processes and
define appropriate controls for measurement and analysis to
identify non conformities and potential non-conformities
• There should be a formal procedure in place that vividly
describes the nature of deviation and recording format
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• N/B: There is no one correct way of designing
the SOP but SOP must be clear, unambiguous
and understandable
13
HOW MERRY
IS THIS
CHRISTMAS?
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Types of Deviation
1) Planned Deviation
2) Unplanned Deviation
Planned Deviation
Planned deviations are described and pre-approved
deviation from the current operational, document,
system, procedure or process covering a specified
period of time or number of batches
It is the prospective handling of timely restricted
departures from approved procedures and
requirements which are intended to happen only once 15
(i.e.temporary)
Types of Deviation (Cont’d)
• These are deviation from procedure that
are foreseen and known before they occur
i.e. they are prospectively agreed and
approved changes
• Planned deviation shall be approved
before execution
16
Types of Deviation (Cont’d)
• E.g. of Planned deviation
Change in Batch Size
Change in Manufacturing Processes
Change to source of API
17
Types of Deviation
Unplanned Deviation
An uncontrolled event in the form of non-
compliance from the designed systems or
procedures at any stage of manufacturing,
packaging, testing, holding and storage of
drug product due to system failure or
equipment breakdown or manual breakdown
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Types of Deviation (Cont’d)
• These are deviation that are unforseen and
unknown before they occur
• E.g. of Unplanned Deviation
Equipment Breakdown
Human errors in dispensing
Power failure during manufacturing
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Sources of Deviation
• Internal
• External
Internal Sources of Deviation
Non conforming materials or product
Not following procedures
Staff observation
Self inspections
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Sources of Deviation
External Sources of Deviation
Customer Complaints
Adverse Events
External/Regulatory Audits
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Example of Deviations Commonly found
During Audits
• Out-of-Specification
• Out-of-Trend
• Failure to follow GMP procedure
• Stability Failure
• Foreign material
• Change in Primary Packaging Material
• Environmental parameters
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Example of Deviations Commonly found
During Audits
• Labeling error
• Documentation error
• Data/calculation error
• Deviation from processing limit
• Deviation from SOP
• Yield limit failure
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Example of Deviations Commonly found
During Audits (Cont’d)
• Visual defect/AQL failure
• Equipment/Instrument Failure
• Environmental Conditions
• Utility failure
• Unapproved changes
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Example of Deviations Commonly found
During Audits (Cont’d)
• Performing activity without proper training
• Outside of operating parameters or in process
control limits
• Failure to follow written SOPs or approved batch
instructions
• Missing entries, unexplained, improper
correction or edits on official records
• Environmental monitoring over alert or action
limits
25
DEVIATION HANDLING
• A robust deviation handling procedure should
include the following
Event (Deviation) Detection
Deviation Classification (or Categorization)
Deviation Treatment
Root Cause Analysis
Corrective Action and Preventive Actions (CAPA)
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Event (Deviation) Detection
• Recognizing an event as deviation when it occurs is pivotal to
detection and this depends largely on:
i) Personnel level of training
ii) Regular use of SOPs
iii) Personnel Qualification
iv) Commitment and support from top
management
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Event Detection (Cont’d)
• The essence of deviation detection is NOT for victimization or to
hunt for blame but to encourage continuous improvement
• Detection should involve
- Identify deviation,
- Inform Supervisor
- Correction
- Document i.e. 1) Description in record
2) Fill-out and issue deviation report (as
required by SOP)
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Deviation Classification & Categorization
• Incidents
• Critical Deviations
• Major Deviations
• Minor (other) Deviations
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Deviation Classification (Cont’d)- Decision
Tree
Event
Product Consumption
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NO may harm Consumers YES
Deviation Classification
(Cont’d)
• Incidents
- This is an irrelevant event, not impacting on
product’s quality
- Should be documented (In a logbook) in case
it needs to be retrieved later as part of an
investigation
31
Deviation Classification
(Cont’d)
• E.g.
- Temporary power failure in warehouse where
no temperature sensitive materials are stored
with no temperature excursions from
established range
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Deviation Classification
(Cont’d)
• Critical Deviations
- When a deviation affects CQAs, critical
process parameter or an
equipment/Instrument critical for process or
control of which the impact to the end user,
personnel or environment is highly probable,
including life threatening situation, the
deviation is critical
33
Deviation Classification
(Cont’d)
- Critical
deviations requires immediate action
- It must be investigated, documented by the
appropriate SOP
E.g.
- Improper line clearance for diazepam tablets
prior to the packaging of paracetamol tablets
- Use of expired or rejected API
34
Deviation Classification
(Cont’d)
• Major Deviation
- When deviations affects CQA, critical process
parameter and equipment/instrument critical for
process or control of which impact to patient,
personnel or environment is unlikely, it is a major
deviation
- It requires immediate action, investigation and
documentation as indicated by appropriate SOP
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Deviation Classification
(Cont’d)
E.g. of Major Deviation
- Untrained personnel
- Use of unapproved reference standard to test
API or drug product
- Product quality attribute out of range for a
non-critical parameter
36
Deviation Classification
(Cont’d)
• Minor deviation
- Deviation does not affect any product quality
attribute, critical process parameter or an
equipment/Instrument critical for process or
control then it is a minor deviation
- Requires documentation
37
Deviation Classification
(Cont’d)
E.g. of minor deviations
- Inadequately trained persons performing
cleaning activities in a secondary packaging
material warehouse
- No particulate monitoring in a class D
environment at “in operation” occupancy
state.
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Deviation Classification
(Cont’d)
N/B:
- Classification of deviations should be based
on thorough understanding of the process,
objective and justified criteria
- Examples cited may be categorized differently
with proper justification
N/B: A class of deviation may be escalated
to the next higher level if the deviation is
repeated in a significant number of times 39
DEVIATION TREATMENT
• For Minor Deviations
- Description of deviation
- Correction (i.e. immediate action taken based on
simplified analysis of the deviation)
Correction should be QA approved before
implementation if and where possible. Do not
necessarily require investigation aimed at identifying the
root cause of the problem as major and minor deviation
do
- Efficacy and conclusions – Efficacy of correction is
verified based on immediate outcomes and accordingly
documented
- Keep Log of deviation.
40
-
Deviation Treatment (Cont’d)
• For Major and Critical Deviations
- Description
- Perform Root Cause Analysis/Investigation
(using appropriate tools such as 5whys, Fishbone
diagram, Brainstorming, Cause and Effects. Key
step in handling major and critical deviation)
- Perform Risk Assessment
(Using Risk ranking, FMEA etc.)
- Batch Disposition (where applicable) 41
Deviation Treatment (Cont’d)
- Initiate CAPA (Corrective Action – Actions taken to
eliminate cause of deviation
based on investigation. Prevents
a recurrence of deviation
Preventive Action- Action taken
to eliminate potential non-
conformities or deviation.
Prevents occurrence of
deviation)
- Keep Log of Deviation
42
Deviation Treatment (Cont’d)
- Evaluate Effectiveness of CAPA
- Conclusion (Summary of observation, summary
of CAPA, batch disposition ,final outcome and
Close out)
- Trending (Continuous/Routine Verification)
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DEVIATION MANAGEMENT FLOW
CHART
• WHAT WHO
•Identify deviation Operatives
•Inform Supervisor Operatives
• Correction Supervisor + Operative
Event • -Document (Description in record) Operatives & Supervisor
Detection ( (Fill out and issue Deviation Report Supervisor/HOD
• WHAT WHO
• Categorize Deviation Using Decision Tree QA team
Deviation
Classification
• Serial number
• Date of observation of deviation
• Functional area where deviation occurred
• Product material involved including batch
number/ analytical report number
• Equipment/Utility involved including
identification number
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Suggestion for Deviation Register (Cont’d)
• Method/Manufacturing stage
• Name of personnel involved in deviation
• Short description of deviation
• Classification (Major/Minor)
• Correction including completion date
• Corrective action including completion
date
• Close-out date 46
Suggested Parameters for
Trending
• Product/Material
• Equipment/Utility
• Method/Manufacturing stage
• Functional area
• Name of personnel responsible
• Classification (Major/Minor)
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