DEVIATION

A deviation is any departure from approved processes, procedures, instructions, specifications, or established standards.

In the pharmaceutical industry, deviations can occur during drug product development, manufacturing, labeling, packing, sampling, testing, storage, distribution, and other processes.

The deviation definition can vary slightly depending on the regulatory authority and requirements governing the company’s processes.

 Some definitions of deviations according to different regulatory organizations and requirements are as follows.

International Organization for Standardization (ISO):

According to ISO 9001:2015, deviations in the context of quality management systems refer to the positive or negative effect resulting from a divergence from the expected or established standards.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH):

In the ICH Q7 Good Manufacturing Practice (GMP) guide for active pharmaceutical ingredients, a deviation is defined as a departure from an approved instruction or an established standard.

Food and Drug Administration (FDA):

In the FDA’s guidance on quality management systems for the pharmaceutical industry and current Good Manufacturing Practice (cGMP) regulations, a deviation is described as a result that falls outside the expected range or fails to fulfil a specific requirement.

 There are two main classification types of deviations: planned and unplanned deviations.

Planned Deviation

Planned deviations refer to pre-approved and intentional deviations from standard procedures or processes. These deviations are planned and justified in advance, serving various purposes, such as process improvement, method validation, and temporary process changes.

Some examples of planned deviations include:

• Implementing a temporary manufacturing process change to test and validate potential efficiency improvements.
• Using an alternative raw material as part of a trial to assess its suitability without affecting product quality.
• Temporarily adopting an alternative testing method to validate its accuracy and reliability compared to the standard method.

Change control and change requests are essential components of managing planned deviations in a controlled and systematic manner.

 Change request documents are part of the change control process. They provide a formal and structured way to propose and justify the planned deviation, outlining its purpose, scope, and potential impact.

 The change control process in the pharmaceutical industry ensures that relevant personnel can assess and approve the proposed change, considering its implications on product quality, safety, and regulatory compliance.

 Implementing planned deviations through these processes helps maintain control, traceability, and well-structured documentation.

Unplanned Deviation

Unplanned deviations refer to a departure from approved procedures without prior notice or intention. Various factors, such as equipment malfunction, employee error, environmental events or others, can cause them.

Unplanned deviations can significantly impact product quality and safety and such deviations should be investigated promptly to identify the root cause and prevent them from happening again.

 Some examples of unplanned deviations include:

• The sudden breakdown of manufacturing equipment leads to deviations from standard operating conditions and affects product quality.
• Deviations are caused by unforeseen events like power outages, extreme weather conditions, or natural disasters that disrupt manufacturing.
• Accidental introduction of foreign materials into the production process, leading to material contamination and deviation from product specifications.

Companies employ Corrective and Preventive Action (CAPA) processes to effectively address and resolve unplanned deviations.

 When an unplanned deviation occurs, the CAPA process is used to implement corrective actions, aiming to mitigate the immediate deviation impact. Afterward, preventive actions are developed to avoid the recurrence of similar deviations in the future.

 The CAPA process implementation varies based on each specific company’s established procedures. Companies assess the severity and categorization of the deviation based on risk to determine whether the CAPA process will be initiated.

How Are Deviations Categorized Based on Risk?

Deviations are categorized based on risk levels to assess their potential impact on product quality, patient safety, and the regulatory requirements companies are subject to.

Companies can have different criteria for defining deviation categories, which are well-described in their protocols and procedures. The categorization of deviations may vary based on the nature of the product, industry requirements, and the company’s risk management needs.

The risk-based deviation categories usually include:

1. Incidents
2. Minor deviations
3. Major deviations
4. Critical deviations

Incident

An incident is an unplanned or uncontrolled event that does not directly affect the manufacturing process parameters or product quality.

Incidents are generally unrelated to GMP requirements and are often not considered deviations.

However, an incident affecting product specifications can be categorized as a cGMP-related nonconformance.

This categorization varies between companies and must be clearly specified in the company’s procedures.

 Examples of incidents are listed below:

• Accidental material spillage occurred in the cleanroom.
• Personnel not appropriately dressed inside the production area.
• A minor typographical error in the documentation that does not affect the overall process or product outcome.

Minor

A minor deviation involves divergences from established procedures or standards that have a noticeable but limited impact on product quality or regulatory compliance.

 Examples of minor deviations are listed below:

• A slight variation in the size or appearance of a product that does not affect its efficacy or safety.
• A deviation in the production timeline that leads to a slight delay but does not compromise the overall product quality.
• Documentation errors that do not compromise data integrity.

Major

A major deviation indicates a significant departure from established procedures or standards that can considerably impact pharmaceutical drug quality and regulatory requirements.

 Examples of major deviations are presented below:

• A deviation in the manufacturing process results in an out-of-specification (OOS) product requiring investigation and corrective actions to prevent further occurrences.
• A failure of critical equipment during production leads to a significant delay in the manufacturing process and a potential impact on product quality.
• Mix ups of cartons of same product with different strength.

Critical

A critical deviation denotes a severe nonconformance from established procedures or standards that poses meaningful risks to product quality, patient safety, or compliance with applicable requirements.

Examples of critical deviations are given below:

Contamination of a critical raw material used in the production process that may lead to a serious health risk for patients.

• Issues in the packaging process that result in incorrect labelling or dosage instructions which can pose a high risk of incorrect medication intake and patient harm.
• Failure to process step during manufacturing.
• Use of obsolete batch document / test method.

 Deviation Management Process Flow

The deviation management process flow follows a systematic approach to identifying, reporting, investigating, documenting, correcting, and preventing deviations from approved or established standards. It outlines how to handle deviations in a structured and organized manner.

The deviation management process flow typically follows the following steps:

1.  Identification
2. Reporting
3. Investigation
4. Documentation
5. Implementation

Identification

The initial phase involves understanding the event that led to a deviation. Deviations can arise at any stage during the product manufacturing lifecycle.

As mentioned earlier, these events are classified as incident, minor, major, or critical, depending on their severity and potential impacts.

The correct categorization helps in prioritizing deviation resolution and determining the appropriate level of investigation and corrective actions required to address each type of deviation.

Companies can create their own categories and select the relevant ones using dropdown menus when drafting deviation-related documents.

Reporting

The Deviation Report holds significant importance in the deviation management process. It is a formal document used to record and document each identified deviation.

The Deviation Report provides a comprehensive account of the deviation, including its nature, location, date, time, personnel involved, and potential impact on product quality or safety.

 It is necessary to be as clear and accurate as possible in the details provided when reporting a non-conformance to aid the investigation.

When a deviation occurs, the department responsible for the process where the deviation took place is usually responsible for filing the Deviation Report. Timeliness is essential in this phase, and the report should be filed within a specified timeframe.

Investigation

After identifying and reporting the deviation, the next step is to conduct a thorough investigation to determine its root cause.

 Root-cause analyses are particularly crucial for major or critical deviations, as they have a significant impact on product quality or compliance with regulatory requirements.

 There are a number of tools that can help us succeed in this sometimes-overwhelming process of deviation management. The relevant Department manager & The QA department, with the full cooperation of relevant department(s), initiate the investigation. This may be done using one or more of the following approaches:

FISHBONE Analysis (Ishikawa/ Cause and Effect Analysis) – meeting participants agree on a problem statement and then brainstorm all causes.

5W1H

In cases where root-cause analysis is required, after completion, the investigation phase proceeds to assess the need for Corrective and Preventive Action (CAPA).

CAPAs are initiated depending on specific criteria established by the company, such as recurring issues and deviations that affect the overall product quality or regulatory compliance.

This systematic approach ensures appropriate actions are taken to address deviations, improve product quality, and maintain compliance with regulatory requirements.

 Documentation

The deviation management process must be documented. This includes the documentation of the identification of the deviation, the investigation, the corrective action, and the preventive action. Deviation-related documents can be linked together to promote traceability of information.

An essential component of deviation management documentation is the audit trail, which maintains a chronological record of all actions and changes made during the process.

Audit trails provide transparency and accountability, as well as evidence that requirements have been met, facilitating efficient tracking of deviations throughout their lifecycle.

Implementation

During the implementation phase, corrective and preventive actions are put into effect to prevent the deviation from happening again in the future. Effectiveness checks should be conducted to ensure that the actions are having the desired effect.

Timely and effective implementation of these actions is essential to ensure continuous improvement and maintain product quality and compliance with regulatory requirements.