“Nonconformity” investigation is a very common term used in production and product quality improvement areas in the pharmaceutical and medical devices industries. It is mandatory and a regulatory requirement.
When non-conformity investigation processes are carried out systematically and thoroughly, the better the effectiveness of the implemented corrective and preventive actions will be. The CAPA process is one of the cornerstones of GMP in the pharmaceutical and medical device industries.
Investigation processes according to “root cause analysis” methodology must be implemented at pharmaceutical and medical device companies.
For the CAPA process to be performed to meet regulatory requirements, it must be assimilated in and an integral part of the company organizational culture. Sometimes it is very difficult to establish an effective CAPA system in large companies.
On the other hand, for midsize companies, or those with a single production site, where relevant functions are familiar with each other and work closely together on a daily basis, it is much easier to establish an effective CAPA system. When it comes to big companies, a simple yet systematic approach is recommended to achieve the best and desired outcome.
Often, “problematic” CAPA systems can be a result of an insufficiently systematic approach and lack of relevant procedures. In this case, large companies may have an inefficient CAPA system because of discrepancies between the different production sites.
Non-conformities may be handled by separate units and sometimes differently for each site, resulting in communication difficulties, inefficiency and wasting of resources.
Large organizations should establish a basic CAPA system and cross-organizational processes that will enable the company to examine the processes performed in the organization and to implement preventive measures that will be effective for the entire organization.
- Correction: Action taken to eliminate nonconformity. The correction can be made in conjunction with corrective action.
- Corrective action: Action taken to eliminate the cause of a detected nonconformity or other undesirable situation.
- Preventive action: Action taken to eliminate the cause of a potential nonconformity or other undesirable situation, to determine what steps must be taken to neutralize the cause of any potential nonconformity and to prevent their recurrence.
- Root cause analysis: Investigation done to understand and reach the root of the nonconformity.
- Most of the time, CAPA investigation begins within a specific event, such as a laboratory investigation, inconsistencies in the manufacturing process, GMP audit or customer complaint. All of these nonconformities are to be investigated using CAPA methodology.
In general, the recommended process of root cause investigation will include the following steps:
- Corrective Action
• Identify the non-conformity, including customer complaints review.
• Evaluate the scope of the nonconformity, including risk assessment.
• Evaluate the need to take action to assure the nonconformity will not reoccur in the future.
• Investigate using all relevant functions in the company (engineering, maintenance, QA, production, process engineering, QC, etc.).
• Analyze, identify and document the root cause of the nonconformity.
- Corrective action
• Determine corrective actions to be taken, responsibilities and implementation timelines.
• Document the corrective action implementation (actions, results etc.)
- Corrective action effectiveness and time lines
• The effectiveness of the corrective action(s) implemented should be presented in objective and measurable manner.
• Verify whether the nonconformity was resolved.
• Verify if the implicated solution can be qualified or validated.
• Verify that the solution implemented will still be effective in the future.
- Preventive action
• Identify potential problems and nonconformities.
• Examine the need for action aimed at proactively preventing the recurrence of a nonconformity/potential problem (or problem that almost happened).
• Analyze, identify and document the root cause of the nonconformity.
• Determine and implement the necessary preventive action(s).
• Document testing procedures and results.
• Determine the effectiveness of the implemented preventive action(s).
Examples of Topics Handled Using Corrective Action Mechanisms
- Delay in product delivery
- Machine breakdown
- Lack of customer satisfaction with the product
- Trends in customer complaints
- Product quality problems
- External or internal GMP audit reports
- Risk analysis
Examples of Topics Handled Using Preventive Action Mechanisms
- Unstable production process which can produce a low quality product
- Safety problem identification
- Trend analysis
- Product and/or system annual reviews
- Temperature variation
- Single raw material supplier
- Risk analysis
- Staff meetings
- Management review discussions
- Customer feedback
Root Cause Analysis
- Make sure that the investigation is performed correctly so that the root cause analysis is identified clearly.
- Avoid root cause processes that will support your initial theories regarding the investigation.
- Avoid ignorance of other possible causes of nonconformities. Focus on the process itself, rather than factors such as employees in general or specific employees, in particular concerning the root cause of a nonconformity.
- Avoid focusing on a single cause. There may be several factors together that are the source of the nonconformity.
- First, understand what is causing the problem. Then, continue investigating until the root cause can be identified. Focus on the whole process instead of on the direct cause of the nonconformity.
- Use statistical and other relevant tools such as a Pareto chart, risk analysis, 5 Why’s, fish bone diagrams, flowcharts, etc.
Many CAPA systems are managed manually. But sometimes, to make the CAPA system more efficient, we need to use quality management software.
CAPA investigations should include an orderly flow chart describing the various stages of the process. Quality management systems can also provide a clear indication for the status of a specific CAPA and the general status of the whole CAPA process, which activities were carried out, who is responsible, etc.
Organizational culture has a crucial influence on successful CAPA system implementation. It is recommended that employees understand the importance of the CAPA system and its great contribution to the GMP compliance of the company.
In order to initiate the CAPA process correctly when a nonconformity is discovered, the manufacturer needs to ask the following questions:
- What is the nonconformity?
- Where does/did the nonconformity occur?
- How often does it happen, and what is the scope of the nonconformity?
Once we know what the cause of the nonconformity is, we can move forward to the next step of tests and experiments. Companies should ensure that investigations are performed according to the CAPA system, should examine all possible causes, and explore the most suspected ones, to determine beyond any doubt the real reason for the nonconformity.
After identification of the root cause, corrective and preventive actions will be implemented to complete the entire CAPA process. The company must distinguish between the symptoms and the root cause. Organization employees should remember that the CAPA system is a tool which improves product quality and the business bottom line.
- Understand what the real problem is that caused the nonconformity.
- Document a clear description for what was observed, why, where, when, what, etc.
- Avoid identifying the solutions. First, focus on identifying the problem.
- Record your observations and collect as much as data as you can for decision makers.
- Analyze the data using charts, graphs and/or images to clearly describe the nonconformity.
- Describe the nonconformity clearly and document your description.
- Avoid including suggestions for solutions in the description of the nonconformity.
- Corrective actions which must be repeated indicate that the problem was not resolved the first time, and therefore that the CAPA process was ineffective and should be revised.
- Identify what action(s) was/were implemented to correct the nonconformity, and what happened as a result.
- Try to examine the effect of the CAPA on the whole process and not only on part of it. Remember that action(s) may have an impact on the whole process.