Deviation in
the pharmaceutical industry:
What it is
and what to do when it occurs?
“Any departures from pharmaceutical
quality are called deviations and can occur at any point during a process or
product lifecycle. Deviations can impact system integrity, product quality and
public health and safety”.
“Deviations are the measured
differences between the observed and expected or normal values for a product or
process condition or a departure from a documented standard or procedure”.
A deviation may occur during
testing and sampling of finished products and raw materials acceptance and manufacturing.
Deviations can also be found out by
the complaints given by the customers or comments given by the customer when
the company’s standards do not meet the critical quality attributes as per the
requirements.
For the sake of continuous
improvement and compliance to Good Manufacturing Practice (GMP), if any
deviation occurs from the official procedures, then it must be documented. Food
and Drug Administration (FDA) part 211.192 requires a thorough investigation of
any deviation including documentation of conclusions and follow up.
Quality Risk Management (QRM)
principals employed in the firm should make sure that all the deviations occurred
are rectified and recorded.
Read Also: Quality Risk Management (QRM)
Deviation
Handling
Among the crucial elements of the quality management system (QMS), handling the deviations plays an important role to assure the quality of the product by continuously improving the quality of it. As a part of Corrective and Preventive action (CAPA), if the deviation is once detected, then it needs immediate action (i.e., corrections), the root cause analysis should be done and systemic actions need to be implemented (i.e., corrective actions) to prevent non-conformances in the future. Recently, QRM is being used to prevent the risk of deviations in the pharmaceutical industry. International standards like International Conference on Harmonization (ICH) guideline Q9 (ICH Q9) and World Health Organization (WHO) recommends using QRM system in the pharmaceutical industries. If any deviation occurs, how the personnel reacts to it is the main challenge to a system. This mainly depends on the level of training, qualification, commitment and support from the higher authorities of the company.
In order to record, classify and
investigate the events based on their risk, decision tree will be used so that
the person can make proper decisions regarding it. The decision tree explains
the simplified assessment of risk which answers the following questions (fig. 1).
Whether the events affect the
quality of the product? Do the approved specifications or written procedure
which is examined, conflict with a requirement?
Types
of Deviations
Deviations are of two types: Planned deviations, unplanned deviations
Planned
Deviations:
Any deviation from a standard procedure selected
intentionally for a short period to avoid undesirable situation without
affecting the safety and quality of the product or procedure.
E.g.: Batch executed with lower input due to unavailability
of raw materials.
Unplanned
Deviations:
Unplanned deviations are the accidental nonconformance
observed after or during the implementation of an activity. Unplanned
deviations may occur due to the following reasons: Equipment breakdown,
Interruption of Power supply, Site Accidents, Utility Breakdown, Errors during
documentation.
Deviations may be further categorized into 3 types
based on the impact of the deviation on the product quality, safety and
validation state of the facility and process. Critical, major, minor
Critical deviation:
The deviation will have a notable impact on the
critical attributes of the product.
For Example: Usage of contaminated raw materials and
solvents. Integrity failure of high efficiency particulate air filters.
Major Deviation:
The deviation will or may have a notable impact on
critical attributes of the product. For Example: Critical process and in
process parameter failure. Significant variation from standard output range.
Minor Deviation:
The deviation will not have any direct impact on the quality
of the product.
For Example: Weights not replaced properly after use.
Equipment and measuring device malfunction.
Procedure for
Handling of Deviation
When to raise a deviation:
As soon a deviation occurs it should be immediately
reported to Quality assurance (QA) within one working day from the time when
the deviation has occurred or as per the Standard operating procedure (SOP).
Record the issue in the deviation record, the time of
occurrence and name of the department and the person who observed it should be
documented. Standard against which the deviation occurred should be recorded.
The general flow for handling of deviations in depicted in fig. 2.
Initial details:
All the initial details regarding the deviation should
be mentioned. All technical details and critical process parameters should be
recorded. Track the progress.
Investigating
deviations:
Establish what happened, understand the events, Use
investigation tools, Identify the causes and check for any common causes. Check
if any other materials, components, batches and equipment are affected?
Root Cause
Analysis
Root cause analysis is a systematic process for
identifying “root causes” of problems or events and an approach for responding
to them. Root cause analysis can be identified and classified as errors caused
by Men, Material, Machine, Method and Mother Nature.
Tools for
identifying the Root cause
Fishbone analysis:
A fishbone diagram, also called a cause and effect
diagram, is a visualization tool for categorizing the potential causes of a
problem to identify its root causes. A fishbone diagram is useful in product
development and troubleshooting processes to focus the conversation. After the
group has brainstormed all the possible causes for a problem, the facilitator
helps the group to rate the potential causes according to their level of
importance and diagram a hierarchy. The design of the diagram looks much like a
skeleton of a fish. Fishbone diagrams are typically worked right to left, with
each large “bone” of the fish branching out to include smaller bones containing
more detail (fig: 3).
5 whys analysis:
5 Why analysis is used as a tool in root cause
analysis. It is a set of five questions to find out the base of the problem.
Sometimes, it is necessary to find out by asking more than 5 questions. Ask a
question ‘why’ repeatedly to know the root of the problem until you find out
the correct root cause.
For Example:
Why the machine was stopped suddenly?
Answer: Due to human error.
Why did the human error occur?
Answer: Human suddenly pressed the stop button.
Why did the human press it?
Answer: The label on the button was not visible.
Why was the label not clearly?
Answer: Because it was covered with dirt.
Why was it covered with dirt?
Answer: It was not properly cleaned. Therefore, here
we understand that the root cause is no proper cleaning practice.
Fault Tree Analysis (FTA):
Fault tree analysis is a tool to find out the root
cause analysis for the deviations. This helps to evaluate the failure of system
one at a time and sometimes, by identifying the casual chain of events,
multiple causes can be combined (fig. 4).
The results of these events are
represented pictorially in the tree form. FTA is used to investigate the
deviations and complaints to understand the root cause and to make improvements
so that it does not lead to further problems. Few other tools for identifying
the causes are: Pareto charts, brainstorming, flowcharting, change analysis.
Closure of the Deviations
Prepare an investigation report for the occurred
deviation and explain what happened and why did it happen. Identify the Root
cause for the deviation. Write corrective and preventive action. Finally,
Quality Assurance shall review the reports and proceed further for the closure
of the deviation. [fig. 5]
Difference among Calibration, Validation and Qualification
User Requirement Specifications
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