Deviation Management Process Flow

Deviation Management Process Flow
A deviation is any unwanted event that differs from the approved processes, procedures, instructions,
specifications, or established standards. Deviations can occur during the manufacturing, packing, sampling, and
testing of drug products.
Deviations are not to be feared – they help the company understand where the problems are and give
us the opportunity to fix them. Through corrective and preventative actions (CAPA), we make sure they
do not happen again!
Always
&
Deviation and CAPA are tools for improvement and growth of the company.
There are three types of deviations, critical, major, and minor
 A critical deviation affects the quality of a critical process parameter, equipment, or instrument
or has an immediate patient safety risk or life-threatening situation.
 A major deviation impacts a product’s quality, safety, or efficacy but may not have a direct
impact on patients.
 A minor deviation affects a utility, equipment, material, component, or documentation but does
not affect product quality or the physical state of the product or its labeling.
GMP requires deviations to be documented. This assists with continuous improvement.

FDA § 211.192 requires a thorough investigation. The Quality Management System should ensure that
deviations from established procedures are identified and recorded.
The responsible department along with quality assurance should evaluate the scope of the deviation,
potential quality impact, trends relating to similar products, materials, equipment, and testing
processes, a review of similar causes, regulatory commitment impact, other batches that could
potentially be affected, and market actions.
 Investigation of critical deviations should be completed within 15 working days

 Investigation of major deviations within 20 working days
 Investigation of minor deviations within 30 working days.
The deviation management process flow has 5 main phases:

1. Identification
2. Reporting
3. Investigation 3A. Root Cause Analysis 3B. CAPA
4. Documentation
5. Implementation
Arvind Kumar Srivastava , Mobile No. 9817039581 , Email ID: arvindsri82@gmail.com Page 1 of 15
1 2 3 4 5
Identification Reporting Investigation Documentation Implementation
Its a First Steps to identified Report as per the respective SOP Data Collection , Data Gathering Once the investigation into the To verify or check the effectiveness
the untoward / Non conformity of untoward / Non conformity / & Data Analysis which are events are complete, it will need of CAPA for a events.
/ problematic events are problematic events are occurred. relevant to the non conformity . to document the root cause and
occurred. Involved the Subject Matter the resultant CAPA plan for To verify the all required
Experts on process, equipment tracking. documents / procedure , system are
Different source for the same or system under evaluation. well established , verified for CAPA
like deviation , Incident , If any change in the documents / effectiveneness & implementated.
Market Complaints, Out-of- process /system as suggest in the
Specification, Out-of-Trend etc. CAPA that will be change through
the change control . Ensure that the events / particular
deviation will not occur again.
Corrective actions should be QA
approved before implemented
and their efficacy verified in a
documentated manner and the
activities related to CAPA that
could require a significant period
of time .
Root Cause Analysis
Root Cause Analysis Method

use to identified the root cause
analysis by using 6M , 5 Why &
Trending.
Root-cause analyses become
necessary when the deviation is
a major or critical one. This
means that the deviation will
have a significant impact on the
overall quality of your product or
cGMP.
A root-cause analysis is not
needed if the deviation is labeled
as an incident or is a minor
deviation
CAPA
Once the root-cause analysis is

complete, the next step in this
phase is to determine whether a
CAPA is needed.
A CAPA is typically initiated
when the root-cause analysis
shows that the issue is recurring
and systemic.
CAPA is not initiated if the
deviation does not impact the
overall quality of your product or
cGMP.
verify the mitigation action plan
that the events may not happen
again.
Training to be imparted.
Approved the CAPA
To Verify the Effectiveness of
CAPA for a Events.
Sr. No. Name of Steps Description
1. Identification It is first step is to get a clear picture of the untoward/ Non conformity / problematic
deviations event that took place. Different sources of non-conformity include, but are
Gather all details not limited to, deviation handling, market complaints, Out-of- Specification, Out-of-
and categorize the Trend, etc. or Deviations can occur during the sampling and testing of raw materials
deviation as an and /or the finished product before packaging. You may get complaints from
incident, minor, customers or notifications when your products have not met the necessary industry
major, or critical standards.
deviation. If any incidence of non-conformance or deviation from approved process or
specification occurs at the manufacturing site, it shall be logged as per the respective
SOP.
An individual (referred to as the Investigation Initiator) who observes or identifies an
incident in which a non-conformance, discrepancy, or failure of Good Manufacturing
Practice has occurred, must record the incident on an appropriate document (i.e.,
Investigation Form or Worksheet) and must notify a higher level of supervision. In
case the individual does not have access to the means to document the non-
conformance, he will notify the matter to the higher level of supervision or a Quality
Assurance individual for documentation and further action. The information to be
documented in the investigation form or worksheet is provided in below section (refer
Defining the Non-conformity).
The initiator or the department supervisor shall take immediate action (i.e.,
containment action) to stop the variant condition from continuing and shall notify QA
of the non-conformity, and decide immediate course of action and potential product
impact based on available information.
The initiator and QA shall make an assessment of the variant condition to determine
the impact of the non-conformance on safety, quality, identity, purity and strength of
the affected product.
Based on the assessment by the initiating department and QA, any component(s)/bulk
products/ finished product which might have been affected by the failure shall be
quarantined and stored as per the respective product storage condition till the
investigation is completed and the decision regarding disposal is made.
QA shall review the non-conformance document, verify the impact of the non-
conformance and classify the non-conformance as ‘Major’ or ‘Minor’ as per the
applicable SOP followed at the respective manufacturing sites.
AT this First steps , QA shall determine whether an interruption / break pause /
stoppage or suspension of the activities is required or not.
2. Reporting Record all deviations the deviations as per the SOP.
The department in which the deviation has occurred usually files the deviation report.
The maximum time frame that is allowed is up to a day after identifying the problem.
During this phase, the concerned personnel will need to provide all details for aiding in
the investigation.
3. Investigation Once you have identified and reported the deviation, you need to determine the root
cause of the deviation. The concerned department along with the QA department will
do a root-cause analysis.
Investigation shall be carried out by the initiating Department where the non-
conformity has occurred. When required, a cross-functional team shall be identified by
the respective Department Head and QA Head to carry out the detailed investigation.
The team members shall be Subject Matter Experts on process, equipment or system
under evaluation.
The respective Department Head and Head QA shall ensure that the investigation is
completed within a pre-defined time line.
The investigation shall include steps defined below:
 Defining the non-conformity : The non-conformance observed shall
be fully documented.
 The product under investigation
 Quality system problem under investigation
 Process problem
 The event description leading to the investigation
 The area effected
 Data collection: All the relevant data related to the non-
conformance shall be collected and documented. The data
collection shall include review of various documents relevant to the
non-conformity, which may include, but shall not be limited to, the
following;
 Review of similar incidences/failures in last two (2) years.
 History of the product.
 Batch production and control records.
 Equipment log books.
 Material usage and inventory records.
 Test data.
 Maintenance records.
 Cleaning records.
 Training records.
 Relevant environmental monitoring records as applicable.
 Records of various utilities used.
 Stability data.
 Product development reports.

 Validation/Qualification reports.
 Equipment/Instrument calibration records.
 Standard operating procedures.
 Annual product reviews.
 Interview/s with operating personnel.
During investigation all above documents are reviewed by the investigation
team. If required relevant persons of the investigation team may visit the
site/place to understand the situation and also review/evaluate the relevant
procedure/practices followed.
 Data analysis:
The data collected during the review shall be analyzed using techniques like
trend analysis, histograms, Pareto analysis, regression analysis, etc. as
appropriate.
 Root cause analysis:
Root cause shall be established based on the observations during
investigation and analysis of available data using tools like Cause-and-Effect
diagram, FMEA, 5 Whys, Fault Tree analysis, etc.
If the root cause cannot be established based on the available data, the most
probable cause(s) shall be identified using the knowledge of the process and
available data.
 Experimentation to confirm causes:
If the root cause is not established based on the available data, then
experiments may be planned or review of unit operation may be carried out
to collect additional data to confirm the root cause. Before carrying out the
experiment, the objective and the experimental plan shall be clearly defined
and documented in the experiment protocol which shall be reviewed and
approved by QA. The results of the experimental study shall be documented,
evaluated and approved by QA in order to draw the conclusions.
 If the investigation report indicates human error as the cause for
the non-conformance, then further evaluation shall be done with
respect to following aspects:
 Clarity of instructions in procedures.
 Adequacy of training.
 Adequacy of supervision.
 Experience of the person.
 Negligence/dereliction of duty.
 Past history of such incidences in last two (2) years.
 Fatigue.
 Any circumstantial trigger, e.g., receiving more than usual work assignments
on that day.
 Psychological state of the person on that day.
 Adequacy of the infrastructural support for job delivery, e.g., in hardware
design, whether there is any inherent problem with the machine that is
responsible for the non-conformity.
The investigation team/QA shall review investigation documentation for accuracy and
ensure that the intended scope, type of classification, level of investigation and other
parameters are appropriate.
3A. Root Cause Analysis 6M/ISHIKAWA/Fishbone diagram/Cause and Effect Diagram Technique
Method use to Purpose: to break down (in successive layers of detail) root causes that potentially
identify the root contribute to a particular effect i.e. The fishbone diagram identifies many possible
cause analysis by causes for an effect or problem.
using the below The Fishbone diagram includes the potential cause of the problem and is used in
mentioned order to find the real causes.
1. FISHBONE Ishikawa diagrams (also called fishbone diagrams, herringbone diagrams, cause-and-
Analysis (6M /
effect diagrams, 6M or Ishikawa) are causal diagrams that show the causes of a
Ishikawa / Cause
and Effect Analysis) specific event. Common uses of the Ishikawa diagram are in product design and
2. 5W1H
quality defect prevention- in order to identify potential factors causing an overall
3. 5 WHYs
4.Fault Tree effect. Each cause or reason for imperfection is a source of variation. Causes are
Analysis (FTA).
usually grouped into major categories to identify these sources of variation.
This tool is mainly categorized in 6M i.e., Man, Materials, Machine Method,
Measurement. The categories typically include as below :
 Man / People: any person/s involved with the process. or Responsible
persons who involved in the process or activity.
 Methods: how the process is performed and the specific requirements for
carrying out the process, such as policies, procedures, etc. or It includes all
procedures, rules, policy, regulation, and specific requirement for the
activity or process
 Machines: any equipment, computers, tools, etc. required to accomplish
the job or Any equipment, instrument involved in the activity or process
 Materials: raw materials, parts, etc. used to produce the final product. or
Raw materials, items, parts used or involved in the process or activity.
 Measurements: data generated from the process that are used to evaluate
its quality. or Data generated during a process which measures the quality
of products. Environment/Milieu This includes environmental conditions
like temperature, humidity, pressure differential etc. and culture which
process or activity performed
Personnel/Men power/Man:
 Skill, knowledge, competence and attitude.
 Adequacy of supervision & support.
 Clarity about job role.
 Experience, training.
 Shift in which the activity done.
 Conduct work environment. Availability of tools/equipment.
Materials:
 Change in source of materials.
 Change in process.
 Age of materials vs. stability.
 Materials packing.
 Test result at incoming stage/retest.
 Storage condition.
 Correctness of quality.
 Quality trend.
Machine:
 Age of equipment.
 Calibration and maintenance history.
 Whether machine operating correctly.
 Machine capability.
 Operating parameters.
Measurement:
 Method validation.
 Analyst training.
 Instrument calibration.
 Standard used.
 Frequency of inspection.
 Other analysis done along with the failing batch.
 Execution of methodology.
Method:
 Whether the process is well defined.
 Critical control points & adequacy of control parameters.
 Robustness of the process.
 Experience, training.
 Process capability.
 Recent change, if any.
 Deviation in execution.
 Trend analysis of process parameters. Safety mechanism and challenges.
Mother environment/Milieu:
 Impact of environment condition on the process.
 Control of environment condition.
 Impact of environmental condition on the material.
Five WHYs 1 H Technique
5 Whys is an iterative interrogative technique used to explore the cause-and-effect
relationships underlying a particular problem.
The primary goal of the technique is to determine the root cause of a defect or
problem by repeating the question "Why?". Each answer forms the basis of the next
question.
1. 5W1H (who, what, where, when, why, how) is a method of asking questions about
a process or a problem taken up for improvement.
2. Four of the W’s (who, what, where, when) and the one H is used to comprehend
for details, analyze inferences and judgment to get to the fundamental facts and
guide statements to get to the abstraction.
3. The last W (why) is often asked five times so that one can drill down to get to the
core of a problem.
4. 5W1H of Six Sigma explains the approach to be followed by exactly understanding
and analyzing the process, project, or problem for improvement.
Who What When Where Why How
Place /
Person / Thing / Time / Reason / Steps /
Location of
People Concept Situation Objective Method
Occurrence
Example:
Problem: Dissolution failure in tablets.
Why? – High disintegration time.
Why? – Over lubrication.
Why? – More mixing in force feeder.
Why? – Slow machine speed with high feeder RPM.
Why? – Parameters not defined in BMR.
The root cause investigation process is a key step in handling major and critical Events
(Market Complaint / Incident / OOS / OOT/ non-conformity).
The Events (Market Complaint / Incident / OOS / OOT/ non-conformity) investigation

report shall be prepared by the respective department and reviewed by Department
Head, Investigation Team and other relevant departments as applicable.
The investigation report shall contain the following:
Summary of findings of the investigation.
Reference to protocols and any other documentation of results.
Evidence that supports conclusions of the investigation.
Impact assessment.
Immediate measures that are planned and recommended based on the identified
root cause or the most probable cause. The immediate measures may include
remedial measures as well.
Requirement of corrective action and preventive action.
The investigation report and supporting documents shall then be forwarded to QA to
determine adequacy and completeness.
QA shall review the investigation, the root cause of the non-conformity as identified
based on the investigation and the necessity of corrective action and preventive
action.
Corrective action shall include action to eliminate the root cause and preventive action
shall focus on elimination of probable causes.
If corrective action and/or preventive action is not recommended by the investigation team
based on the investigation findings and the type of non-conformities, then scientific
justification/rationale shall be provided in the investigation report for not recommending
corrective action and/or preventive action.
 Who was involved in the in the process.

 Who shall have been involved.
Person /
Who  Who is currently doing it.
People
 Who shall be involved in it.
 Who is investigating it.
 What is to be done.
 What is being done.
Thing /  What has done.
What
Concept  What should have done.
 What are the targets.
 What are the control.
 Mfg. Process to be relooked

 Testing to be relooked.
 Issue in Quality parameters.
Time /
When  Human errors.
Situation
 Performance of Man, Material , M/C.
 Manufacturing process & test method
suitability.
 Manufacturing process execution
 Raw material receiving , sampling , testing ,
Place / dispensing etc.
Where Location of  In-process checking and analysis
Occurrence  FG sampling & Testing
 Specification and Test Procedures
 Reporting & Reviewing Data.
 Why manufacturing process
 Why test method
 Why machinery
Reason /
Why  Why man
Objective
 Why material
 Why process controls
 Why quality
 Process Management
 Process improvement
 Defining Measuring
Steps /
How  Analyzing Control
Method
 Process design / redesign
 Verification of process manufacturing and
test method.
3B. Corrective and In regulated life sciences industry / pharmaceutical company, serious quality issues can
Preventive Actions
and do occur.
(CAPA) -
( Review of Once the thorough investigation done by investigation team convenes and performs a
investigation and
root cause analysis for a events to remedy the issue , after root cause analysis for a any
CAPA)
outcomes of a events (complaints, product rejections, non-conformances, recalls,
deviations, audits, regulatory inspections and findings, and trends) , create corrective
and preventative action (CAPA) to be fix the quality issues and ensure that do not
occurs again such types of events .
The pharmaceutical company should have a system for implementing corrective

actions and preventive actions resulting from the investigation of complaints, product
rejections, non-conformances, recalls, deviations, audits, regulatory inspections and
findings, and trends from process performance and product quality monitoring.
Corrective Actions are taken to eliminate the root causes of Events (Market Complaint
/ Incident / OOS / OOT/ non-conformity), and should be based on good quality
investigations.
A structured approach to the investigation process should be used with the objective
of determining the root cause.
Corrective and preventive action should result in product and process improvements
and enhanced product and process understanding. The Corrective and Preventive
Action plan shall be adequately documented along with methods for evaluating the
effectiveness of the measures and acceptance criteria.
CAPA should be used and the effectiveness of the actions should be evaluated.
3Ba. Effectiveness of Effectiveness of CAPA may be checked by doing trial runs with laboratory/commercial
CAPA
scale batches. Planned CAPA shall be implemented following Change Control
procedures. Implementation in commercial production shall be done in conformance
with the regulatory pathway.
Documentation Once the investigation into the events are complete, it will need to document the root
cause and the resultant CAPA plan for tracking.
If any change in the documents / process /system as suggest in the CAPA that will be
change through the change control .
Corrective actions should be QA approved before implemented and their efficacy
verified in a documented manner, activity that could require a significant period of time.
Corrective actions should be QA approved before implemented and their efficacy
verified in a documentated manner and the activities related to CAPA that could require
a significant period of time .
Completion of investigation:
QA shall close the investigation. The investigation must be completed within thirty
(30) working days of detection of the non-conformance. However, investigations
which may require more than thirty days for completion can be extended based on
rationale/justification duly approved by QA and as per procedure defined in
respective SOPs.
The investigations, in such cases, shall be completed as per the new timeline
decided.
An interim investigation report with status as on date shall be submitted in such
cases.
Once the investigation has been closed, it may be reopened to amend the original
report as a result of additional data or information related to the original investigation.

Such amendments shall be approved by the same functions that approved the original
investigation.
Monitoring of CAPA System:

Implementation All corrective and preventive action plans shall be implemented within the target
To verify or check
completion date mentioned in CAPA.
the effectiveness of
In case the CAPA could not be implemented within the target completion date in a
CAPA for a events.
few cases, a revised target date should be documented along with justification and
To verify the all
approved by Site Quality Head.
required
Methods For Verifying Effectiveness
documents /
The below mention methods are verify the Effectiveness of CAPA
procedure , system
Trend analysis In cases of human error, training, environmental monitoring
are well established
excursions, cleaning deviations, testing errors, etc., trend analysis can help you
, verified for CAPA
determine if the corrective action has remediated the issue. Review data over a
effectiveneness &
predetermined timeframe and determine if the problem or deviation has occurred
implementated.
again (or as frequently) after the corrective action was implemented. In most cases,
Ensure that the
events / particular the data will tell you if the fix was successful, or if another corrective action should
deviation will not be established.
occur again.
Periodic checks This method involves scheduling a time for the quality unit to
review the process that was remediated. For example, if there was a CAPA
implemented to improve gowning practices, the auditor can observe the newly
improved gowning practices prior to the operator entering the clean room.
Surprise audits Audits are intended to ensure that the operators, process, or
equipment is following the prescribed corrective action documented in the CAPA.
One other benefit of surprise audits is that the reviewer gets to observe the daily
occurrences in the area and the how the solution is working in the area affected.
Sampling Sampling is a successful method to verify corrective actions pertaining to
environmental monitoring or lab testing. For example, if there was a deviation for
an area exceeding environmental action limits, and more robust cleaning practices
were installed, additional samples could be taken to verify that the new cleaning
protocol was effective.

Deviation Management Process Flow

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Deviation Management Process Flow

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Deviation Management Process Flow

There are three types of deviations, critical, major, and minor

GMP requires deviations to be documented. This assists with continuous improvement.

 Investigation of critical deviations should be completed within 15 working days

The deviation management process flow has 5 main phases:

Root Cause Analysis Method

Once the root-cause analysis is

 Product development reports.

Who What When Where Why How

The Events (Market Complaint / Incident / OOS / OOT/ non-conformity) investigation

 Who was involved in the in the process.

 Mfg. Process to be relooked

The pharmaceutical company should have a system for implementing corrective

report as a result of additional data or information related to the original investigation.

Monitoring of CAPA System:

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