Automation & Control / QRM Process

CAPAS: Too Much or Not Enough?

A strategic CAPA plan requires transparent information and a clear understanding of root causes.

Corrective and Preventive Action (CAPA) is a critical part of pharmaceutical quality systems. Failure to comply with requirements can be costly for any pharmaceutical or biopharma company, resulting in damaged reputation and profitability. But adhering to CAPA is not only a regulatory requirement — it’s sound business practice. This article examines issues and presents best practices.

FACT: CAPA continues to top citations for 483s and warning letters for pharmaceutical companies.

FACT: Despite the progress being made in ICH Q10 Quality Systems discussions and other frameworks, during the past two years, an increasing number of pharmaceutical quality issues and recalls have made newspaper headlines. Have pharmaceutical CAPA programs evolved, and are they moving in the right direction?

From a regulatory perspective, CAPA implementation and effectiveness is a key indicator of overall Quality Systems effectiveness, yet many drug companies still struggle to achieve and maintain compliance. The overarching reason is that many facilities and companies are still using a variety of manual, semi-automated and homegrown systems.

Smallerscale reasons include the following: CAPA is an independent piece of the quality system and often viewed as “Quality’s job.”

  • In some cases, an organization’s processes are fragmented and disconnected.
  • Procedures are not always well documented.
  • Required process steps are not always completed.
  • Employees don’t always know or understand their individual level of responsibility or authority.
  • Not all source inputs to potential nonconformances are identified.
  • Information is not measured, monitored or shared across different product lines or business units.
  • Trending data are not always visible to the appropriate level in the organization.
  • Companies tend to neglect to look into the processes and procedures of their quality systems. Their focus is on product rather than the efforts to resolve systemic issues, or they fast-forward to a solution without really identifying the root cause.

For all these reasons, pharmaceutical companies can have difficulty following and enforcing standards and consistent procedures, or using trending data that is visible to the entire organization, to predict quality across all products and processes. In many facilities or companies, there is no real-time visibility of compliance and quality activities.

Moreover, a lack of good reporting and trending capabilities makes it difficult for top management to make accurate assessments about the issues, risks and especially costs facing the organization. Not only disconnected systems, but a lack of fully closed-loop processes across key compliance systems can prevent pharmaceutical manufacturers from harnessing the data that would minimize surprises and give them an early warning of impending problems.

How can pharmaceutical companies improve their CAPA systems? The first step toward improvement is thinking about CAPA holistically, and recruiting and training the employees who will operate the system. An effective CAPA management system revolves around a global program, trained employees, well-documented SOPs and proper utilization of technology to institute global practices and procedures.

Focal Points Planning – The foundation of a successful CAPA system is adequate planning and setup. Before establishing a CAPA system, you need to define code rules and ownership. The following questions need to be addressed:

  • What are the rules and variances to the rules?
  • What are the processes and who are the owners?
  • What will the failure modes be?
  • How will severity levels be defined?
  • Who will enter the information?

Remember that the nonconformance control/CAPA system should be scalable, simple, risk-based, and easily integrated throughout the organization. Ensure that sufficient mechanisms are in place so that all steps are completed for each event. It’s very important that you determine whom to involve in the CAPA process and when.

You will need to decide how procedure revisions will be handled and how you will enforce rules and procedures on a global level.

Source Error Tracking – Many companies may lack connected data sources. At numerous others, the crossreferencing of source errors, deviations and other events across files, dates, batch lots and other criteria is done by hand, requiring a significant amount of time and creating opportunities for impacts and trends to be missed. This approach leads to serious inefficiencies and continued repetition of mistakes.

The first step is to identify, collect and record any information that can occur anywhere throughout your product or process’s value chain. You will need to identify everything from problems that may occur at business partners’ sites, through the final manufacturing, labeling and distribution life cycle to any possible customer complaints. The key to recording problems is to drive to the root cause and focus on prevention and correction actions. The more knowledge you have, the faster you can react. Tracking problems will allow you to develop best practices and verify effectiveness.

The system may build upon existing infrastructure, but eventually all data should be routed to one location. Without an integrated system, identifying root causes is little more than guesswork. Assumptions are made based on rumor and conjecture, rather than accurate, reliable data. Islands of information created by multiple data streams lead to inconsistencies and waste. Real measuring tools enable managers to determine precisely where and when mistakes are occurring and why.

A sole repository of information for the organization, which includes external and internal inputs from product life cycle, processes and quality systems, ensures that supervisors and managers can quickly access information, compare and contrast solutions to determine best practices, and monitor overall performance. In other words, when a company has a closed-loop nonconformance control and CAPA system, with a few clicks of the mouse, a manager can see what’s happening company-wide, rather than having to review multiple documents and files.

Trending, Analysis and Risk Management – Once source-error information is correctly captured, many companies escalate these immediately to CAPAs to begin the investigation process. This behavior, enforced by FDA on good investigations and by the company’s own internal policies to close CAPAs within a short time period, may lead to an overload of data that doesn’t inherently reveal the critical impact of what’s failing across the organization.

With a volume of CAPAs, a company can become too overwhelmed to assure the effectiveness of its Corrective/ Preventive action plans; to determine what the trending actually shows; and if the information provided back to product design is going anywhere. Use the data you collect to detect minor problems quickly before they become major problems. Change the behavior of your employees by applying risk techniques throughout the CAPA program.

The progress of risk management has been seen in many companies that have implemented risk mitigation plans and assessed failures as part of the overall product formulation and development cycle. However, such risk techniques have been left to the front or back part of the process, leaving each designated department (QA/Manufacturing, R&D) to track, trend or analyze data individually. Progressive companies need to adopt and integrate risk techniques as part of the nonconformance and CAPA process to correctly categorize and prioritize those critical problems: focus.

For these critical CAPAs, the company’s Risk Management Team should be integrated into the investigation and root cause analysis process of the CAPA itself, where analysis shouldn’t be left to just product but also process, therapy and users/usage (route of administration). This will help increase the view of critical problems to management and help each department focus on the key areas of impact for both effectiveness and overall product and process improvement, moving an organization from reactive to proactive.

Trending is still a key within an organization to monitor the pulse-point of an organization’s overall health of its quality systems. Implement measurement, data analysis tools, and processes for different levels of the organization. Assure that there are linkages within between products, processes, quality systems, and across multiple divisions and/or facility locations. Configure data such that problems related to product, process, or the quality system can be identified and acted upon quickly. Leverage as much information as possible to draw targets and assess effectiveness. Harmonization of sources, failure and root cause codes is essential to drawing meaningful conclusions.

Results of the analysis and/or any further decision to take action are identified as an output of the nonconformance/CAPA system. Change can be a result of a CAPA process or a part of your continuous improvement initiative. Regardless, by taking the information you have gathered and analyzing it, you are able to detect areas where you can improve and change. The CAPA process should be tied to a company’s overall change management strategy to more effectively respond to issues as they arise.

Employee Accountability and Management Visibility – Drive for employee understanding and ownership (accountability) by implementing consistent and sustainable practices and a tiered training program. Train employees at all levels of the organization, and across departments, on sound investigation methods, good documentation techniques, and the meaning/purpose of all CAPA elements. Management can encourage employees to embrace quality throughout the organization by instigating new programs.

Provide a bonus for compliance factors:

  • Timely implementation and documentation of CAPA
  • No 483 observations
  • Getting (or keeping) the CE mark Alternatively, institute a disciplinary system for noncompliance:
  • Letters of reprimand for not meeting commitments
  • Dismissal for repeated failure to comply

Closed-loop CAPA processes allow management to see where the problems exist across their organizations and how effective their current processes are. When fully integrated into an organization, a closed-loop CAPA system can positively affect operational performance and move organizations from a reactive posture to a more proactive one.

The focus of such a system is prevention and correction of deviations, which in turn reduces bad batches, generates fewer regulatory warnings and recalls, and boosts company profits and customer satisfaction. In addition, with the data you collect, you can monitor the cost of quality and provide key metrics to management to help justify further investments in CAPA and global quality systems.

Quantify the cost of noncompliance by calculating:

  • Waste
  • Customer complaints
  • Corrections and recalls
  • Delays in IND and NDA clearance
  • Suspension of government contracts
  • Not getting certificates for product for export
  • Shutting down of your operations
  • Product liability actions
  • Shareholder lawsuits

Such trending of data can not only help you with improvements but also help the organization realize that preventive action is cheaper than corrective action. It’s all about the business More and more companies are adopting continuous process improvement and implementing closed-loop, integrated CAPA across the enterprise. A constant flow of information across your value chain can reduce time to diagnose and resolve problems, avoid supplier shortfalls, and help to meet customer expectations.

The collaboration that is required to bring products to market faster and safer, avoid regulated actions and improve customer satisfaction demands an integrated CAPA system to plan and manage all variability, risks and visibility. Close the circle of quality assurance by developing, implementing, and maintaining a closed-loop CAPA system that integrates compliance into business practices and quality systems. Use your CAPA system to improve profitability by decreasing the cost of quality. High cost of quality impacts the bottom line (waste, delays in product approval, resource inefficiency, etc.).

Drive actions based on data and risk in order to help determine where to focus actions and resources. By detecting and reducing errors across the enterprise, quality and therefore customer safety improves. A well developed CAPA process is critical to reducing risk, improving customer satisfaction, reducing variability, and keeping product quality visible across the organization.


About the Author

Nikki Willett is vice president of Marketing & Regulatory Products at Pilgrim Software.

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