Ensuring CAPA lives up to its name

June 20, 2024
How pharma can use CAPA as a tool to support continuous process improvement

Corrective and Preventive Action (CAPA) is not a new quality record by any means — it has been a critical component of pharma quality management systems (QMS) for a very long time. In fact, an organization does not have a QMS without one, even if it is paper-based.

That said, CAPA was not intended to be a QMS compliance tool only; its intent is in fact defined by its name. It is a system or process for analyzing, correcting and preventing issues. CAPA applies to products and processes alike and it is meant to support continuous improvement. Ultimately, CAPA’s target isn’t compliance, although that is one of its roles; it is improving patient outcomes.

Pharma organizations, along with all life sciences companies, need to be sure their CAPA process has not become a checkbox item in their QMS and is instead being used as a tool to support continuous process improvement. However, CAPA can’t be used to support continuous improvement if it is not analyzing causality to prevent reoccurrence. Additionally, if CAPA actions are not being prioritized based on risk, CAPA will become a compliance burden rather than an improvement tool with bottom line impact for the business. If it has become a rote process, mechanical in its execution, chances are improvement is not being achieved.

CAPA effectiveness must be measured individually and over time. So how does an organization make sure its CAPA process supports continuous improvement and lives up to its name and intent?

Assessing risk

Let’s start with risk. To support continuous improvement organizations must prioritize CAPAs by focusing on the issues that have the most impact on patients, product quality and the organization overall. This means focusing on the highest risk issues first.

There are varying schools of thought on how to measure the risk of a CAPA. To measure risk, organizations must know what could happen or what did happen.

Formal tools for defining the ‘what’ and performing risk assessments include but are not limited to:

  • failure mode and effects analysis (FMEA)
  • fault tree analysis
  • hazard analysis and critical control points (HACCP)
  • hazard operability analysis (HAZOP)
  • preliminary hazard analysis (PHA)
  • risk ranking

Informal risk assessment methods include:

  • brainstorming
  • impact assessments
  • statistical tools

FMEA, which is the most often used to identify, analyze and prioritize risk, is resource intensive and requires skill and experience with the technique itself. For this reason, it’s a method that is used less frequently in pharma, however there is progress being made towards applying it more.

When conducting a FMEA, the risk assessment output is known as the risk priority number (RPN). It is calculated as follows: RPN = severity (S) x occurrence (O) x detection(D). The RPN is the risk score for each failure mode. There is some debate in the industry regarding the use of the RPN. There are those that believe risk should be viewed as a continuum and therefore one cannot assign nor calculate risk numerically. Some also disagree with the utilization of ‘detection’ in the calculation, as it can put focus on issues with much lower severity that are difficult to detect.

That said, FMEA and RPN (with or without detection) is a way to systematically evaluate risk. It is consistent and it removes subjectivity as much as possible. It is also widely accepted by regulatory bodies.

HACCP in pharmaceuticals is traditionally used to identify, assess and control safety hazards and pinpoint where they might occur in the drug manufacturing process. This preemptive action is taken to prevent hazards from occurring. By monitoring and controlling each step in the process, the risk of the hazard occurring is minimized.

HAZOP is also focused on using a systematic approach to identifying potential problems and assessing the safety of designs, processes and operations. A structured method for risk management, a HAZOP study is one of the leading techniques used to identify potential standard and compound technology failures in the production process and to eliminate or reduce the probability of occurrence. HAZOP is a critical tool in pharma manufacturing as failures in manufacturing process controls can lead to contamination, potency issues, and a litany of other product problems — not to mention the harm it can cause to manufacturing personnel.

Collectively, all of these techniques are quality risk management tools that define not only what could or did happen (the problem) but also the risk involved with the potential or actual failures for a product or process. Understanding the problem is the first step in the continuous improvement process. You cannot improve what you don’t understand and correcting what isn’t a problem compounds the risk that new issues will be introduced while the original issue remains.

Determining root cause

The CAPA process also involves assessing the cause — you cannot correct an issue or prevent (eliminate) a problem’s occurrence if the root cause of the issue can’t be determined. For this reason, once we understand what has gone wrong, it is important to understand why an issue or issues occurred. It is equally important to determine if there is more than one root cause for the issue(s). Additionally, it is critical that organizations ensure that the investigation they are performing is properly scoped.

Determining root cause involves performing a solid root cause analysis. Root cause analysis tools may include but are not limited to:

  • 5 whys
  • fishbone
  • scatter plot diagrams
  • histograms
  • Pareto charts
  • brainstorming

From the above list, 5 whys is the most widely used tool across industries, pharma included. It is the process of asking why repeatedly to ensure that companies move beyond the obvious symptoms to discover the root cause. The key is that an iterative interrogation is completed to determine cause and effect for a problem.

The fishbone diagram, a process also known as the Ishikawa diagram; has the same goal: to look at cause and effect to determine root cause. It is a more structured process than 5 whys because it looks at several contributing factors for the problem — personnel, materials, measurements, machines, methods and environment.

Choosing which root cause process is deployed within a company is dependent on the company’s products and organizational preferences.

Investigations into what went wrong along with its risk and root cause cannot come only from predefined spreadsheets. Understanding the problem (what), the risk (seriousness) and the cause can only be achieved through thorough analysis. It is important to reiterate that CAPA can only be used to support continuous improvement if it is analyzing causality. If the CAPA investigation is not getting to the root cause(s), the wrong problem is being addressed and therefore continuous improvement is not possible.

Effectiveness review

Corrective actions must correct and prevent recurrence. To accomplish this, companies must address the true root cause or causes, rather than higher-level causes that are too generic. In addition to that, organizations must guard against having only cookie cutter actions predefined for issues. Doing so will only lead to the same result and same effectiveness.

Therefore, the final step to ensuring that CAPA supports continuous improvement is to include an effectiveness review. During an effectiveness review, an action plan will lay out the steps or tasks needed to measure and determine whether the CAPA has or has or hasn’t eliminated the issue.

The action plan tasks should be clear, detailed and contain no ambiguity. To ensure action innovation, be sure that CAPA doesn’t become a task assigned exclusively to the quality assurance team. Making the process inclusive ensures that ideas from other disciplines within the organization can be considered and that everyone is aware of changes to be made.

However, simply checking if the actions taken are effective over a certain period of time is not enough. Instead there needs to be a plan in place to identify what determines effectiveness, including qualitative and quantitative measures to determine effectiveness. Meaning that the criteria for acceptance and the tasks associated with determining acceptance are well defined. There needs to be appropriate justification for the verification of effectiveness and the sampling plan as well.

Without appropriate measurable effectiveness reviews, organizations could find themselves doing the same things over and over again, making little or no headway in correcting their issues, much less achieving continuous improvement of the process.

Keeping CAPA fresh

Pharma organizations need to be sure their CAPA processes haven’t become checkbox items in their QMS. CAPA is a process that can get stale if an organization is not paying attention. Assessing trends in CAPA effectiveness, monitoring root cause depth and accuracy, and assessing risk over time is key to achieving continuous improvement through the CAPA process.

It’s important to note that the FDA calls out ineffective CAPA procedures and investigations often. While CAPA is a regulatory requirement, it’s intended to correct and prevent. CAPA’s real value lies in its ability to support continuous process improvement, enhancing  product efficacy while optimizing organizational impact.

To achieve continuous improvement as an industry and move CAPA beyond compliance, we must embrace discovery and discard cookie cutter approaches that serve only to get the CAPA completed on time. While CAPA can strengthen an organization’s performance, more importantly, it improves the efficacy, safety and efficiency of pharma products, ultimately improving patient lives.

About the Author

Kari Miller | QMS Regulatory and Product Management Leader

As the senior director of product management for IQVIA’s SmartSolveKari Miller is responsible for driving the strategic product roadmap, and delivery of industry best practices and regulatory compliance solutions for quality management. Kari has more than 25 years of experience delivering software solutions for life sciences. She brings that knowledge to her current team as they focus specifically on translating market and industry requirements into industry-leading enterprise quality management solutions that meet the needs of the heavily regulated life sciences QMS market. Kari earned a Bachelor of Science in Business Administration and a Bachelor of Science in Psychology from Marian College of Fond-du-lac, Wisconsin.