What is Deviation in Pharmaceutical Industry?

A deviation is an unexpected event that occurs during the ongoing operation/ activity/documentation/entries at any stage of receipt, storage and manufacturing, analysis, and distribution of drug products/intermediates /raw materials/ packing materials. deviations are to be reported as and when they occur and to be investigated for impact assessment.

What Is Deviation Management?

• The process of identifying, assessing, and correcting deviations from approved instructions or established standards is known as deviation management. Let us consider the pharmaceutical industry as an example. Your cleanroom's high-efficiency particulate air filters have failed, potentially contaminating one or more batches. This is a critical error that could have serious consequences.
• Sometimes the terms "deviation" and "non-conformity" or "non-conformance" are used interchangeably.
• The former is commonly used in the pharmaceutical industry, whereas the latter is commonly used in the medical device industry. Many life science organizations have streamlined the entire deviation management process by implementing an Electronic Quality Management System (eQMS) that allows for efficient deviation management.

What Are the Different Types of Deviation?

In general, your organization will encounter two types of deviations: 

1. Planned Deviations
2. Unplanned Deviations

Planned Deviations

• Planned deviations are temporary deviations from an existing protocol or process that have been pre-approved.
• They are limited to a specific time period or a number of batches. Your organization makes these changes to avoid a potentially hazardous situation.
• Deviations are planned in such a way that they do not compromise the safety and efficacy of your products.

Examples of planned deviations in the pharmaceutical industry:

1. Change in batch size due to reduced availability of raw materials
2. Change in batch size for a specified number of batches
3. Change in supplier for excipients

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Unplanned Deviations

• Unplanned deviations are non-compliances with your designed protocols or systems that occur at any stage of a product's lifecycle, including manufacturing, testing, holding, packaging, and storage.
• Unplanned deviations are also referred to as unplanned events, uncontrolled events, or incidents.
• They can be caused by human error, utility failure, equipment/instrumentation breakdowns, or malfunctions.

Examples of unplanned deviations in the pharmaceutical industry:

1. Interruption of power supply resulting in equipment breakdown
2. Accident at the site due to human error
3. Disruption of utility services

What are the Deviation Classification Categories?

There are four deviation classification categories 

1. Incident.
2. Critical deviation.
3. Major deviation.
4. Minor deviation.

1. Incident

• Incidents are deviations that do not directly affect the quality of your products. However, they are against Current Good Manufacturing Practices (cGMP).

Examples of Incident

1. Unauthorized personnel in the production area.
2. Material spillage in the cleanroom.
3. Staff not properly dressed in the production area.

2. Critical Deviation

• Deviation that cloud has a significant impact on the production quality or the GMP system.
• Examples of critical deviation are given below but are not limited to :

1. Cross-contamination or product mix–up in a product.
2. Failure to process step during the manufacturing.
3. Use of obsolete batch document/test method
4. Filter integrity failure.

3. Major Deviation

• Deviations that could have a moderate to considerable impact on product quality or GMP system.
• Ex gave below but not limited to:

1. Machine breakdown during processing.
2. Mix-ups of cartons of the same product with different strength

ALSO READ: SOP for Data Integrity

4. Minor Deviation

• The deviation is unlikely to have a detectable impact on product quality or the GMP system. 
• Examples of minor deviations are given below but are not limited to :

1. Minor errors in batch records or documents that do not affect the integrity of the date.
2. Spillage of material during dispensing.
3. Failure to meet environmental conditions during batch processing.

The following flowchart will help you understand the deviation classification process.

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PROCEDURE

• All deviations shall be documented, investigated, tracked, and trended.
• All deviations shall be reported when they occur.
• The person who observes the deviations shall inform the immediate supervisor or concerned department head /designee and to quality assurance.

• As per the severity of deviation and stage of the process, the process may be stopped for the Initial Assessment
• QA shall issue the “deviation control format the request of the initiator (concerned department ) by assigning a deviation number.
• The initiator shall fill the details (like product/material/ equipment/document / other if any and batch no / A.R. No if applicable ) in the deviations control form.
• The initiator shall be initial assessment and shall take suitable immediate action according to the nature of the deviation and inform to department head and concerned QA person.
• The initial impact assessment shall be done by the observing department head/designee and designated person QA. recommendation for continuation of process / discontinues the process shall be given by the head of the department and Head QA of the designee.
• Based on the nature of the deviation, initial assessment and immediate action are taken. The Head of initiating department shall approve the deviation for further evaluation of QA.
• After approval of deviation from the head of initiating department, the deviation form shall be forwarded to QA for evaluation.
• During evaluation designated QA person shall verify whether the deviation is quality relevance or not and whether the deviation is a repeat occurrence or not.
• If it is quality relevance, the impact shall be assessed on other areas/departments.
• And if it is a repeat occurrence, impact assessment shall extend to verify the effectiveness of previous CAPA taken.
• After evaluation categorizes deviation into critical, major, or minor based on the evaluation of impacted areas and product quality impact.

ALSO READ: SOP for Quality Management System

• If the deviation is categorized as critical or major, a cross functions team comprising technical experts from different (as per the nature of deviation) shall be formed to investigate the root cause of deviation.
• If the deviation is minor, an investigation shall be carried out jointly by a designated QA person along with a person from the department where the deviation happened.
• Failure investigation and root cause identifications shall be carried out by the investigation team using investigational methodologies.
• Upon identification of the root cause of failure, the probable root cause of failure shall be documented.
• Corrective actions and preventive actions shall be recommended to prevent the
• reoccurrence of the same.
• The deviation including the investigation report (wherever applicable) shall be closed within 30 working days of the date of the initiation. The initiation date is the date of observation of deviation.
• If deviations are not closed within the specified timeline initiator shall rise the “period extension request“ As per SOP.
• Initiating Department Head shall review the extension request and write a justification for the period of delay with an impact assessment.
• QA shall assess the impact of delay in action completion and approve/reject the period extension request.
• Deviations shall be closed only when all relevant actions in the CAPA long are completed.
• Continuous trending of deviations shall be carried out on monthly basis.
• QA shall carry out trend analysis for all the deviations in the whole year at the beginning of the next year by using monthly trend data. A copy trend analysis shall be forwarded to the head of CQA.
• The record retention for all closed deviation and investigation reports shall be not 7 years or as otherwise agreed with the concerned regulatory body. All deviations and investigation reports shall be kept in the custody of QA and QA shall maintain the deviation register.

EXAMPLE OF DEVIATION

Activity /document	Examples of deviations documents are wrong version date missing or
Procedures (SOPs)	Procedure not followed
Documents	Documents wrongs version, date missing or incorrect date.
Batch records (BMR / MPR)	Steps not followed; step skipped
Incoming materials requiring QA release	Deviations reported by receiving department include damaged or incorrect shipment, missing or questionable labels or documentation
A sampling of incoming materials	Damaged or incorrect shipment, incomplete or incorrect documentation
Material and their status	Incorrect or unapproved material used, questionable release
Batch yield	Established yield or reconciliation is not met
Process control parameters	Parameters not in control and/or not followed
Sampling	Improper sampling technique or frequency, sample identity mix-up
Material holding time and holding conditions	Holding time or conditions not met, an incorrect vessel used.
Environmental controls	Parameters exceed limits.
Calibration	equipment/instrument out of calibration or tolerance, log or sticker missing
Equipment function/facility issues	Equipment/ instrument failure, incorrect equipment/ area used
Quality	Failure errors reprocessing, reinsertion
Date entries	Calculations error, missing of critical reading.
Signatures /approvals	Inconsistent date/initials, inappropriate approvals
Equipment/area cleaning. line clearance, sterilization, and sanitation	Inappropriate cleaning, line clearance failure questionable housekeeping.
Validations/qualifications related deviations	Failure to meet validations/qualification requirements, non-validated equipment, unapproved protocol
Testing	Testing not performed within an established timeframe, testing not performed

Deviation Management Process Flow

The deviation management process flow has 5 main phases:

1. Identification

• Your first step should be to get a clear picture of what happened.
• Before packaging, deviations can occur during the sampling and testing of raw materials and/or the finished product. When your products fail to meet industry standards, you may receive customer complaints or notifications.
• All deviations will be issued and handled by the people in charge of Quality Risk Management in your organization.
• Collect all relevant information and categorize the deviation. As previously stated, the incident can be classified as a minor, major, or critical deviation.

2. Reporting

• Your organization must keep track of all deviations and have a policy in place for reporting them.
• The deviation report is usually filed by the department where the deviation occurred. After identifying the problem, the maximum time frame allowed is one day.
• During this phase, the concerned person must provide all relevant information to aid the investigation.
• You can use QMS software, built-in best-practice forms, and procedures to guide you through the process of documenting all relevant deviation data points. This assists in reducing the margin of human error and making the correct decision.

3. Investigation

• After you've identified and reported the deviation, you must determine what caused it. The concerned department, in collaboration with the QA department, will conduct a root-cause analysis.
• When the deviation is significant or critical, root-cause analyses are required. This means that the deviation will have a significant impact on your product's or cGMP's overall quality. If the deviation is labeled as an incident or minor, no root-cause analysis is required.
• After completing the root-cause analysis, the next step in this phase is to determine whether a CAPA is required.
• When the root-cause analysis reveals that the problem is recurring and systemic, a CAPA is typically initiated. If the deviation has no impact on the overall quality of your product or cGMP, CAPA is not initiated.
• While the QA department approves the CAPA, the responsible department is responsible for implementing and closing the CAPA.
• Similarly, when a deviation occurs, you can use a system like QMS software to determine whether or not a CAPA is required. 

4. Documentation

• When the investigation into the deviation is finished, you must document the root cause and the resulting CAPA plan for tracking purposes.
• It is also critical for your company to keep an audit trail, which is a regulatory requirement.
• Audit trails are chronological records of all actions, events, and changes, including deviation management, root-cause analysis, and CAPA activities.

5. Implementation

• Finally, you will have a deadline to meet as well as a CAPA to complete.

You will ensure that this particular deviation does not occur again during this phase.

You will first describe the problem in CAPA. The scope should be addressed next. Once the problem and its scope are identified, you will implement immediate fixes while investigating the root cause of the problem. Following the completion of the root cause analysis, your company will plan and implement actionable steps (i.e. corrective and preventive actions).

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