CAPAS: Too Much or Not Enough?

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.