Corrective and Preventive Action (CAPA) in the Pharmaceutical Industry: From Deviation to Documentation

Corrective and Preventive Action (CAPA) is a cornerstone of the quality management system in the pharmaceutical industry. It plays a pivotal role in identifying, addressing, and mitigating non-conformities, deviations, and potential risks that could impact the safety, efficacy, quality, and cost-effectiveness of pharmaceutical products. By integrating innovative thinking and practical experience, CAPA supports both compliance and continuous improvement.

Motivated by the importance of this process, I have decided to share my expertise and practical insights on CAPA. This article will provide a comprehensive understanding of the CAPA process, including the definitions and differences between Corrective Action (CA) and Preventive Action (PA), real-world case studies, key elements of an effective CAPA system, practical applications, benefits, and its critical role in fostering a culture of quality. You’ll also find answers to frequently asked questions to help solidify your understanding and implementation of CAPA in a real-world setting.

What is Corrective and Preventive Action (CAPA)?

Corrective and Preventive Action (CAPA) is a systematic and proactive approach used to address current issues and prevent future problems by leveraging innovative skills, experience, and data-driven insights. It focuses on ensuring quality, safety, efficacy, and cost-effectiveness, making it a vital tool for applying lessons learned in a smart and sustainable manner.

In the pharmaceutical industry, CAPA is a structured methodology for identifying, investigating, and resolving nonconformities and other undesirable conditions. The primary goal is to determine and eliminate the root cause of problems to prevent their recurrence. The depth and rigour of the investigation, as well as the extent of documentation, should be proportionate to the level of risk associated with the issue.

CAPA is a fundamental aspect of Good Laboratory Practice (GLP) and a critical requirement under the International Council for Harmonisation (ICH) guideline Q10, which outlines a model for pharmaceutical quality systems. Moreover, it is mandated by the U.S. Food and Drug Administration (FDA) under 21 CFR Part 820.100, emphasising its regulatory significance.

Effective CAPA management enhances product quality, ensures regulatory compliance, and supports continuous improvement across all stages of the pharmaceutical lifecycle.

Mathematical CAPA can be represented as:

CAPA = CA + PA

The two main functions of Corrective and Preventive Action (CAPA)

The following are the two main functions of CAPA:

1. CA or Corrective Action &
2. PA or Preventive Action

CA or Corrective Action

CA aims to identify the root cause of the product and quality problems and take appropriate action against them. It includes:

• Review and definition of a problem
• Identification of the root cause of a problem
• Development of an action plan for correction and prevention
• Implementation of the plan
• Evaluation of the plan’s efficiency

PA or Preventive Action

• Identification of potential problems
• Identification of the root cause of the problem
• Development of a recurrence prevention plan
• Implementation of the plan

Difference between corrective action and preventive action

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The purpose of Corrective and Preventive Action (CAPA)

The purpose of CAPA is to collect information, analyse information, identify and investigate product and quality problems, and take appropriate and effective corrective and/or preventive action to prevent their recurrence

Typical examples of Corrective and Preventive Action (CAPA)

• Customer complains
• Deficiency letters (DLs)
• Failure of the result
• Failure of experiments
• A lot of pharmaceutical product fails quality inspection due to a defect in its critical quality attributes (CQAs)
• SST failure during HPLC and GC analysis

The Role of CAPA in Other Industries

While CAPA is widely used in the pharmaceutical industry, it is also employed in other sectors such as electronics and automotive. These industries face similar challenges, including cost pressures, the need for reliability, and the demand for continuous improvement. The adoption of CAPA and other quality improvement methodologies, such as Six Sigma, has enabled these industries to achieve significant advancements in product quality and performance.

Corrective and Preventive Action Implementation Plan

The following are the 5-step CAPA Implementation Plan:

1. Identification: The initial phase of CAPA is called identification which collects the information from the even,t including the following elements:
   • What is the event?
   • What is involved in that event?
   • Where is the event seen?
   • When did the event happen?
2. Evaluation: The second phase of the CAPA system is the evaluation phase, a very important phase as it also classifies what is, and is not, affected by the event, such as:
   • Is it affecting customer safety?
   • Is it having an impact on regulatory documents?
   • Is this affecting documentation or product design and materials, or product performance?
   • Has this event appeared before?
     • Answers to all these questions provide the basis for the impact assessment of the event to assign a risk level to the event (high, medium, low).
3. Investigation and Root Cause Determination: Once the event has been identified and evaluated, this can be investigated. So, the investigation is the third process in the CAPA system used to determine the root cause as well as identify corrective actions.
4. Resolution Plan: The fourth step in the Corrective and Preventive Action (CAPA) system is appropriate Resolution Plans, having three main categories:
   • Correction: A resolution to an existing problem usually occurs right after the event is identified in order to fix the immediate problem.
   • Corrective Action: A resolution to prevent the reoccurrence of a problem that will address the root cause identified in the investigation.
   • Preventive Action: A resolution to prevent the occurrence of a problem.
   • Once the Resolution Plans are determined, they should be completed on time.
5. Implementation: Implementation is the fifth step of the CAPA system where teamwork is needed depending on the scope of the resolutions. All resolution plans must be documented and these results must also be reviewed and approved by the appropriate Quality Management to ensure compliance.

The final step of the CAPA system is the effectiveness check to make sure the action is appropriate for the root cause and prevents events in the future. Effectiveness checks involve the review of event data, conducting audits of affected products, materials, or equipment, etc

CAPA Case Study: Failure of Impurity profile analysis results in HPLC analysis

Example:

• API “Paracetamol” with the following impurity result was supplied to the customer
• Imp. A: NMT 0.06% (Limit NMT 0.15%), Any unknown impurity NMT 0.05% (Limit NMT:010%) and total impurity NMT 0.11% (Limit: NMT 0.30%)
• When the Paracetamol was analysed at the customer site it failed in impurity “A”. Customer analysis resulted in 0.30% (OOS) for impurity “A”
• Possible root causes:

• Method: The same method was used by the Customer and the Manufacturer
• Column: The same make column was used by the Customer and the Manufacturer
• Chromatographic condition: The same Chromatographic condition column was used by the Customer and the Manufacturer
• Instrument: Same-make instruments were used by the Customer and the manufacturer
• Calibration: Calibrated instruments were used by both the Customer and the manufacturer
• Validation: Calibrated instruments were used by both the Customer and the manufacturer

• From the above details, it is clear that there was no deviation in the analysis. Now, the question is, what is the root cause of the variation in results for impurity “A”?
• Sample preparation procedure: While investigating the sample preparation procedure, it was observed that the sending lab was preparing the sample by sonication at a lower temperature (using the ice in the sonication bath). The customer also followed the same procedure except for the sonication temperature. Sonication was made at room temperature since temperature was not mentioned in the method monograph.
• When the sample was prepared at a low temperature (using the ice in a sonicator bath) the same result was obtained.
• Hence, higher temperature was the root cause of the OOS result for impurity “A”.
• The sample preparation procedure was included in the method

The Desired State: Enhancing Product and Process Understanding

One of the primary goals of CAPA is to enhance product and process understanding. By identifying and addressing nonconformities and potential risks, CAPA methodology helps improve product and process performance, reliability, and quality. It enables organisations to gain insights into the root causes of issues and implement corrective and preventive actions to prevent their recurrence. This proactive approach promotes continuous improvement and ensures the delivery of safe and effective pharmaceutical products.

Components for an effective CAPA system

The following components play a crucial role in effective CAPA implementation:

• FMEA or Failure Mode and Effects Analysis: FMEA is an effective element of a proactive approach, that provides input for the CAPA activities
• APQP or Advanced Product Quality Planning: APQP is generally used in the automotive industry to drive quality improvement in mobility end products
• Strong Governance: A strong governance structure ensures proper scrutiny of corrective actions and timelines, thereby promoting accountability and responsibility throughout the organization.
• Management Review: Regular management reviews allow for the measurement of the achievement of quality system objectives and the assessment of performance indicators. This evaluation helps monitor the effectiveness of processes within the pharmaceutical quality system, including CAPA.
• Robust Business Processes: Well-defined and standardised business processes provide a foundation for effective CAPA implementation. They ensure consistency, efficiency, and transparency in addressing nonconformities and improving product and process performance.
• Standard Methodology: Having a standardised CAPA methodology helps streamline the investigation and resolution process. It provides a structured framework for identifying root causes, implementing corrective and preventive actions, and evaluating their effectiveness.
• Information System: An integrated information system facilitates the capture, analysis, and reporting of CAPA-related data. It enables organisations to track and monitor the progress of CAPAs, identify trends, and generate actionable insights.
• Effective Training: Comprehensive training programs ensure that employees understand the CAPA process and their roles and responsibilities in its implementation. Training helps build a culture of quality and continuous improvement within the organisation.

Lessons Learned from CAPA Implementation

Implementing a successful CAPA system requires organisations to learn from their experiences and continuously improve their processes. Some of the key lessons learned from CAPA implementation include:

• Avoid Overwhelming the System: The sheer number of CAPAs can overwhelm an organisation. Prioritising and focusing on critical issues is essential to ensure effective and timely resolution of nonconformities.
• Set Realistic Timelines: Artificially imposed timelines can lead to rushed investigations and inadequate root cause analysis. Setting realistic timelines allows for thorough investigations and the identification of sustainable corrective and preventive actions.
• Choose the Right Metrics: Selecting the appropriate metrics to monitor CAPA performance is crucial. It is important to focus on a few critical metrics that provide meaningful insights into the effectiveness of the CAPA system and drive the right behaviours.
• Strong Governance and Oversight: Establishing strong governance and oversight mechanisms ensures that CAPA processes are adequately reviewed, monitored, and improved. Regular management reviews and a commitment to quality are crucial to the success of the CAPA system.

The Future of Corrective and Preventive Action (CAPA) in the Pharmaceutical Industry

As the pharmaceutical industry continues to evolve, the CAPA process is expected to evolve as well. Some future trends and developments include:

• Non-Exception Type Data: CAPAs will increasingly be based on non-exception type data, such as data trending and holistic data reviews. This shift will enable organisations to identify potential issues proactively and implement preventive actions.
• Early Implementation in the Development Process: CAPA will be implemented earlier in the product development process, allowing for early detection and resolution of nonconformities and risks. This proactive approach will help prevent significant problems and improve overall product quality.
• Industry and Regulatory Surveillance: Organisations will leverage industry and regulatory surveillance to identify emerging trends and potential risks. This proactive monitoring will enable timely CAPA implementation and ensure compliance with evolving regulatory requirements.
• Cost of Quality Model: The adoption of cost of quality models will help organisations quantify the financial impact of nonconformities and the benefits of implementing CAPAs. This approach will facilitate resource allocation and investment decisions related to CAPA activities.

Advantages of Corrective and Preventive Action (CAPA)

• Better customer satisfaction, safety and security
• Improved productivity and better product quality
• Lower cost of regulatory non-compliance (fines, penalties)
• Audit compliance

Importance of CAPA in QMS (Quality management system)

Corrective and preventive actions (CAPAs) are important in a quality management system (QMS), which ensures continuous improvement and adherence to quality standards.

Conclusion

CAPA is a structured and defined approach that empowers organisations to address various problems and prevent their recurrence through a comprehensive approach to quality management and continuous improvement. It is a versatile tool that can be applied across a variety of industries and provides organisations with the means to identify, investigate, and effectively resolve issues.

CAPA is a vital tool in the pharmaceutical industry, enabling organisations to identify and address nonconformities, deviations, and potential risks. It promotes continuous improvement, enhances product and process understanding, and ensures the delivery of safe and effective pharmaceutical products. By implementing a robust CAPA system and learning from past experiences, organisations can achieve regulatory compliance, improve product quality, and safeguard patient safety. This is all about this post.

I hope this article has helped you understand CAPA and its importance. Now you can independently plan and implement CAPA.

Related:

• Relative Response Factor (RRF) in Pharmaceutical Analysis

FAQS: Corrective and Preventive Action

What are the four stages of CAPA?

Identification, Evaluation, Investigation and Root Cause Determination, Resolution Plan:, and Implementation are main stages of CAPA.

What is the CAPA principle/ rule?

CAPA is a structured approach to investigating and resolving nonconformities and other undesirable situations in the pharmaceutical industry. It aims to eliminate the root cause of the problem and prevent its recurrence in the future

What are the two types of CAPA?

Two types of CAPA are CA or Corrective Action & PA or Preventive Action.

What is CAPA as per 21 CFR?

The CAPA is under FDA 21 CFR 820.100

How many steps are there in CAPA?

There are five steps in CAPA; Identification, Evaluation, Investigation and Root Cause Determination, Resolution Plan:, and Implementation

What is the CAPA life cycle?

The CAPA process follows the Plan-Do-Check-Act (PDCA) cycle to resolve unexpected events.

What are the elements of CAPA?

FMEA or Failure Mode and Effects Analysis and APQP or Advanced Product Quality Planning are the elements of CAPA

What is a KPI in CAPA?

KPIs (Key performance indicators) in CAPA include; Time to resolution: Measure the time from problem identification to successful resolution. Number of Open CAPAs: Track the number of CAPAs running at any time.

How to write a CAPA plan?

Identification, Evaluation, Investigation and Root Cause Determination, Resolution Plan:, and Implementation are the main steps of the CAPA plan

What is the CAPA sop?

The SOP which deals with the implantation of CAPA is called CAPA SOP

How to fill the CAPA format?

The CAPA format is filled into 6 steps Identification, Evaluation, Investigation and Root Cause Determination, Resolution Plan, Implementation and approval

What is the purpose of CAPA?

The purpose of CAPA in the industries is to collect information, analyse information, identify and investigate product and quality problems, and take appropriate and effective corrective and/or preventive action to prevent their recurrence.

How do you write a CAPA report?

The CAPA report is written in 6 steps: Identification, Evaluation, Investigation and Root Cause Determination, Resolution Plan, Implementation and approval

Further Reading

• CAPA-FDA
• ICH Q10

Abbreviations

• CQ: Cost of Quality
• CA: Corrective action
• PA: Preventive action
• SST: System suitability test
• HPLC: High-performance liquid chromatography