Deviation In Pharma 

Author: Mr. Prashant  Suresh  Devmore,                   Mail Id: prashantdevmore@hotmail.com

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Quality has prime importance. Nowadays, many substandard products have been manufactured and sold. But the products with optimum quality will win the race. In pharmaceuticals also, product quality is the biggest concern. Hence the concept of deviation in pharma is developed in pharmaceuticals to evaluate the quality concerns related to pharmaceutical products.

During production time incidents and accidents may happen, that may impact product quality. To handle such failures and to have optimum quality products quality management system plays a crucial role in pharmaceutical companies.

There are ways to handle quality concerns in pharmaceuticals. Like deviations, investigation, risk management, etc. In recent regulatory inspections, inspectors have given the focus to the quality management system of pharmaceutical companies.

The quality management system is devised into the following,

• Deviations
• Corrective and preventive actions (CAPA)
• Change control system
• Out of specification
• Out of trend
• Microbial excursions
• Risk management
• Annual product quality product

In. Last post we have reviewed the out-of-specification system. This post will go through deviations in the pharmaceutical system.

Overview on deviation handling system:

What Is Deviation In Pharma?

In a simple way, deviations are the temporary departures from the established values, specifications, limits, validated methods, standards, documents, standard operating procedures

Deviations are routinely happening in pharmaceutical companies. Many people say that deviations are bad. But I can say deviation will improve the process and makes it more robust. How? Because of the deviations the system gaps will be identified and will be filled by effective implementation of corrective and preventive actions.

Most read posts:

• APQR in pharma: APQR, procedure for annual product quality review, drug manufacturing product quality review, product quality review
• Change control procedure in pharma
• OOS in pharma: OOS investigation, OOS investigation flowchart, OOS investigation procedure

How many types of Deviation in Pharma?

Critical deviations

Those deviations which will impact product quality, patient compliance, and operator safety are called critical deviations.

Major deviation

Those deviations which are impacting the quality of the product are called major deviations.

Minor deviations

Those deviations impact product quality and operator safety, but documentation and procedure impacting deviations are called minor deviations.

Types of deviations

Initially, deviations of two types are planned and unplanned. But nowadays only unplanned deviations are considered. For planned deviations

How to handle deviation in pharma?

When observed, deviations have to be filled immediately. Immediate actions shall be implemented immediately to arrest the current situation/product loss/process loss. Later after filling deviation, the details of immediate action taken shall be mentioned. 

1. How do you write deviation in pharma?

The title of the deviation should include what, where, and when happened. It means the description of the deviation should give proper information of incidence.

Wrong description of deviation:

The product spillage was observed during the manufacturing stage. – this is not the descriptive title of deviation. The title should provide detailed information.

A correct description of Deviation 

During manufacturing of product “XYZ”, having batch no. ABC2021A01, product spillage observed from manufacturing tank T/001, on date 15.05.2021 from manufacturing line I

The above-mentioned title provides detailed information of what, when, and where the incidence happened. This will help to track the details of deviation and for the trending of deviations.

Flow chart of deviation in pharma:

2. Preliminary Investigation of deviation:

The next stage is the spot evaluation. This step is 1^st step of investigation. In this step, the team handling deviation has to visit the location of deviation, to collect more information. Documentary, all things can not be understood. Hence to collect the information of failure, a spot visit/object visit is required.

For detailed investigation, many investigational tools are used. Investigational tools mean the method of investigation. Many times, the root cause of the failure couldn’t be identified. For these multiple investigations, tools are being utilized.

During the initial investigation of deviation, it is mandatory to check the deviation is not repeated. If the deviation is repeat deviation it means the previous CAPA that had been implemented is not effective. However, the same can be justified if the root cause for the repeat deviation is different. Details of repeat deviation are to be mentioned in details of deviations.

What is the method of deviation investigation? What are root cause identification methods?

Below is the list of root cause investigation methods,   

• 5 why analysis
• Fishbone analysis
• Brainstorming session
• Fault tree analysis

The most commonly used method is 5 why analysis. This method is suitable for minor deviations/ however, for critical and major deviations this method is not suitable. Though this method is not suitable if the cause is perfectly-identified, then 5 why analysis method also can be used for major and critical deviations investigation.

If the cause is not getting identified, then the best suitable method is fishbone analysis. In this method, there are 6 M’s. these 6 M are

• Man
• Material
• Method
• Machine
• Milieu
• Measurement

The investigation shall be performed on all the 6 M mentioned above. From the 6 M, many probable causes will be noted and that shall be considered for mitigation.

Fishbone Illustration in pharmaceutical deviations 

The deviation investigation shall be completed within the stipulated timeframe of 30 days. If timelines are overdue, the timeline extension procedure shall be there. The deviations which are impacting to regulatory product, then assessment from the cross-functional team shall be done. 

Based on the investigation outcome, the impact assessment is to be done.

3. What is impact assessment in deviation?

In a simple way, it ensures the impact of identified deviation on other activities, processes, systems, studies, documents but not limited to.

Detailed impact assessment is a must for the deviations. In this phase, evaluation of the impact on existing process, same product, other products, facility, document, systems, methods, financing, the environment must be considered. After identification of impacted items/ objects, the CAPA action shall be there to revise/remove the identified impacted objects/ procedure.

Based on the root cause and impact assessment, Corrective and preventive actions shall be suggested with predefined timelines.

These CAPA actions shall be tracked till implementation. After the implementation of CAPA, CAPA effectiveness checks shall be ensured.

Related posts on pharmaceutical quality management system:

1. Out of specification handling procedure in the pharmaceutical industry

2. Change Control System In Pharma Industry

4. What is corrective and preventive action (CAPA) [CFR Code: 21CFR820.100]:

Corrective and preventive action (CAPA or simply corrective action) consists of improvements to an organization's processes taken to eliminate causes of or other undesirable situations. It is usually a set of actions that laws or regulations require an organization to take in manufacturing, documentation, procedures, or systems to rectify and eliminate recurring non-conformance. Non-conformance is identified after systematic evaluation and analysis of the root cause of the non-conformance. 

Non-conformance may be a market complaint or customer complaint or failure of machinery or a quality management system, or misinterpretation of written instructions to carry out work. The corrective and preventive action is designed by a team that includes quality assurance personnel and personnel involved in the actual observation point of non-conformance. It must be systematically implemented and observed for its ability to eliminate further recurrence of such non-conformation.

Corrective action:

Action is taken to eliminate the causes of non-conformities or other undesirable situations, so as to prevent a recurrence.

Preventive action:

Action is taken to prevent the occurrence of such non-conformities, generally as a result of a risk analysis.

5. CAPA Effectiveness Check:

Effectiveness Check-In Pharmaceutical Deviations

6. Closure of deviation in pharma:

On completion of the investigation, impact assessment, and suitable CAPA identification, the deviation can be closed. However, after successful implementation of corrective and preventive actions, the CAPA shall be closed.

References:

1. FDA: Corrective actions and preventive actions

2. Code of federal regulations reference.