CAPA - SEVEN STEPS FOR AN EFFECTIVE PROCESS

A sound Corrective and Preventive Action (CAPA) programme can be a powerful tool for improving product quality, streamlining production and ensuring regulatory compliance. Yet many pharmaceutical companies' CAPA systems today are falling short.

In the UK's Medicines & Healthcare products Regulatory Agency's (MHRA) inspectorate deficiency trend data for 2016¹, for instance, the most cited deficiency that year was related to companies' quality systems, as it was in 2015. In 324 GMP inspections of pharmaceutical manufacturing plants, including 82 inspections overseas, the agency uncovered numerous deficiencies related to incident investigations and CAPA implementation in 2016.

Examples of CAPA-related deficiencies reported include deviation reports containing insufficient information to describe the investigations conducted or demonstrate the evidence supporting the proposed root cause. In some cases, CAPAs were inadequate or formal CAPAs were not raised at all. Often there was no review of repeated deviations, indicating a failure of CAPAs to resolve the issue. The MHRA also found insufficient investigation or documentation of potential serious incidents, with the objective of determining the root cause and implementing appropriate CAPAs.

Quality event issues will continue to plague companies working in GMP environments until they take the necessary steps to strengthen their CAPA programmes.

To effectively investigate and correct quality issues to prevent recurrence, a comprehensive CAPA process should conduct and track the following seven procedures meticulously:

1. Identify the potential or actual problem

In any effort to implement a CAPA programme, the first step is to clearly define the potential or actual problem, whether it's a non-conformance or system failure. This requires an accurate and complete description of the specific source of the information that initiated the action, as well as a detailed description of the problem and available evidence that the problem exists. The source of information may be external or internal, such as a customer complaint, service request, risk assessment or internal quality audit. The description of the problem should be concise but contain sufficient information to ensure that the problem is easily understood when read. It's also important to specify any available information that indicates the problem exists - for example, steadily increasing downtime may be evidence for a potential equipment problem.

 

An automated CAPA process, from start to finish. Diagramme courtesy of MasterControl

 

2. Evaluate the potential impact and risk level

Once described and documented, the problem should be evaluated to determine the need for action and the level of action required. This involves impact and risk evaluations to gauge the potential impact of the problem and the actual risks to the company and customers.

Part of the evaluation is an explanation of exactly why the problem is of concern, such as its possible impact on costs, product quality, safety or reliability. The result of this impact evaluation should be used to assess the seriousness of the problem. The risk level associated with the problem may affect the priority of actions that are taken - for instance, a problem that presents a serious risk to the function or safety of a product may be assigned a high priority and require immediate remedial action.

3. Develop an investigation procedure

After evaluating the potential impact and risk of the problem, it is important to write a procedure for investigating the problem. To ensure that the investigation is complete and nothing is overlooked, a written plan should include at least the following elements: an objective for the actions to be taken; the investigation procedure and timelines to be followed; and the responsibilities and resources required.

In the written plan, the objective should state the desired CAPA outcome simply, with specific instructions outlining what must be done to determine the problem's contributing and root causes. The investigation procedure must incorporate a comprehensive review and analysis of all circumstances relating to the problem. The procedure should also assign responsibilities to personnel involved in the investigation, in accordance with the determined timeline, as well as identify and document any other necessary resources expected.

4. Analyse the problem using available information

The newly created investigation procedure should be used to investigate the cause of the problem. Analysis involves collecting relevant data, investigating all possible causes of the problem and using the available information to determine the root cause.

The manufacturer should create a list of all possible causes and use it as the basis for collecting relevant information and test data, etc. Results of the data collection - which may include a combination of testing results and/or a review of records, processes, etc. - should be documented and organized. The resulting documentation should address all previously determined possible causes, as it will be used to determine the root cause of the problem. There are many tools that can be used to determine root causes, including failure mode and effects analysis (FMEA), 5 Whys and Fishbone diagrams. Identifying and documenting the root cause is essential for determining the appropriate corrective and/or preventive actions that must be taken.

5. Create an action plan using the analysis

The results of the analysis should be used to develop an action plan for correcting and/or preventing the problem. A CAPA action plan should include at least the following: tasks to be completed; changes to documents, specifications, processes, etc.; personnel responsible for each task; employee training; and an expected completion date.

In the action plan, the manufacturer should list any documents that will be modified and describe the expected modifications in general terms. If any changes to processes, procedures or systems are to be made, they should be described with enough detail that it is clearly understood what must be done, and the expected outcome of the changes should be explained. Employee training is an essential part of any change and thus must also be part of the action plan.

6. Implement and document action plan tasks

Once the CAPA action plan is written and ready to be implemented, the required tasks listed and described in the plan should be initiated, completed and documented. The importance of proper documentation in the process of implementing the action plan cannot be overstressed.

To create an implementation summary, all activities carried out per the action plan's requirements should be listed and summarized, creating a complete record of actions taken to correct, and prevent the recurrence of, the problem. This includes changes, preventive measures, process controls and training, among other important information. All modified documents and/or other specifications should be listed, and any modifications should be communicated to affected personnel and departments. Typically, the documentation will be attached to a final printed report of this CAPA action to help facilitate verification of changes.

7. Verify completion and effectiveness of actions

After implementation of the plan, a thorough evaluation of actions taken is essential to the CAPA process. There are two key points of this follow-up: verifying that all tasks have been carried out to completion, and making sure they were effective.

The implementation and completion of all changes, controls and training, etc., should be verified, and the evidence of these actions' completion should be recorded. Moreover, in verifying the effectiveness of the actions taken, a comprehensive evaluation should be done to ensure the following: the root cause of the problem has been solved; any resulting secondary situations have been corrected; proper controls have been established; adequate monitoring of the situation is in place; and any adverse effects of the actions taken are resolved. This investigation and its results should be documented.

Conclusion

For regulated companies across the globe, an effective CAPA process can be instrumental in identifying and correcting issues and preventing their recurrence in a quality system. Meeting risk-based CAPA requirements today demands a complete CAPA process - from identifying the problem through successful completion.

 

Author:
Alex Butler
... is the Medical Device Product Manager for MasterControl. He currently oversees the development of solutions that help medical device companies increase efficiencies, ensure compliance and accelerate time to market.

Source:
¹ MHRA GMP Inspection Deficiency Data Trend 2016, Updated on 18 April 2017 at https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/609030/MHRA_GMP_Inspection_Deficiency_Data_Trend_2016.pdf