The role of CAPA in pharma

When implemented properly, CAPA in pharma contexts are a cornerstone of compliance, continuous improvement and proactive risk management within a highly regulated sector.

Let's explore what CAPA is, how it fits into your regulatory requirements, and how to apply best practices for implementing an effective CAPA in pharma system.

 

What is CAPA in pharma?

 

CAPA in pharma applies simply to the application of corrective and preventive quality management actions within a pharmaceutical company.

Because pharmaceutical companies are highly regulated and fall within a high threshold of quality and compliance expectations, CAPAs are a critical - usually mandated - pharmaceutical quality assurance technique that's used to fix drug issues and stop them reoccurring.

Let's explore in more detail what CAPA in pharma companies entails.

 

What is CAPA?

 

The CAPA process is a systematic approach used by pharmaceutical companies to address nonconformities and defects in their processes, products and systems.

As the name suggests, CAPA involves two key components:

• Corrective action: This refers to actions taken to address existing problems, such as product defects or process failures. A counter-action is taken to fix the issue and negate its effects.
  
  
• Preventive action: The goal here is to tackle the root cause of the original issue so that it doesn't occur again. Preventive action can also be executed independently of corrective action, by focusing on proactively identifying potential problems before they occur, then putting measures in place to prevent them from happening.

 

For pharmaceutical companies, CAPAs ensure that manufacturing processes meet regulatory requirements, and that any nonconformities are quickly addressed to avoid compromising product quality or patient safety.

 

CAPA compliance in the pharmaceutical industry

 

As you might expect for such an important quality technique, CAPAs in pharma companies are a widespread regulatory requirement designed to ensure the safety, efficacy and quality of drugs.

A robust and effective CAPA system is crucial, as regulatory bodies like the FDA, ICH and EMA expect companies to prove that a CAPA framework is in place.

And it's something pharma companies do struggle with.

One 2012 study at a major pharmaceutical company found that 28% of their serious deviations were directly related to how earlier change controls and corrective/preventive actions had been implemented.

Failure to get your CAPAs right, then, can have long-lasting effects and trigger repeating problems.

And non-compliance and weak CAPAs can bring severe consequences, including fines, product recalls, or even shutting down of your manufacturing operations.

 

Pharma regulatory requirements

 

Global regulatory bodies set out specific guidelines for CAPA in pharma contexts.

Understanding your specific CAPA requirements is a crucial first step to mature and appropriate CAPA processes.

Let's take a look at what a few key regulators say about CAPA in pharma operations.

 

FDA compliance

 

The U.S. Food and Drug Administration (FDA) requires pharmaceutical companies to implement CAPA systems as part of their quality management systems.

CAPA in pharma companies forms part of the FDA GMP requirements which govern how drugs are manufactured and distributed to patients. The FDA expects pharma manufacturers to continuously identify, investigate and correct deviations and defects, while also implementing preventive measures to avoid reoccurrence.

However, CAPA in pharma FDA regulations isn't as well documented as it is in, say, medical device regulations like FDA 21 CFR Part 820 and its Subpart J - even though you'll need strong CAPA processes in exactly the same way.

For that reason, we recommend dipping into other FDA regulations like Part 820, which map out CAPA expectations more helpfully.

During FDA inspections, one of the key areas of focus will be your CAPA system. Suboptimal CAPAs crop up in about 40% of Form 483s issued to pharmaceutical companies - and if your auditor does spot something which needs fixing and issues a VAI or OAI, you'll have 15 days to get together a complete CAPA plan outlining how you'll fix the problem.

An effective CAPA system therefore helps pharma companies avoid and respond to observations, warning letters and other agency enforcement actions like recalls or import alerts.

It also demonstrates that your company takes product safety and quality seriously, and is aligned with cGMP best practice.

 

RELATED READING: What is cGMP in the pharma industry? 7 experts explain

 

 

ICH Q10

 

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) outlines its CAPA expectations in ICH Q10, the global standard for pharmaceutical quality systems.

According to ICH Q10, CAPAs are an essential part of the pharmaceutical quality system (PQS), and are instrumental in fostering continuous improvement across the drug lifecycle.

The guideline highlights that companies should not only address product defects, but also continually monitor their processes for potential risks and areas of improvement.

We can see here how CAPAs constitute one of the four key elements of the Q10-compliant PQS:

 

 

ICH Q10 recommends that CAPA in pharma companies seeking to comply should be well-integrated into the product lifecycle, underpinned by effective knowledge management and feeding in turn into proactive continuous improvement and risk management activities.

More than any other regulation, ICH Q10 emphasizes the interconnected nature of CAPA in pharma operations, and its ability to support and integrate with multiple top-level PQS objectives.

 

EU regulations

 

In the European Union, EudraLex Volume 4, the set of regulations governing pharmaceutical manufacturing, includes strict CAPA requirements enforced by the European Medicines Agency (EMA).

EU good manufacturing practice (GMP) guidelines, such as Volume 4 Annex 1, emphasize the importance of an efficient CAPA system as part of the pharmaceutical quality management process.

Like the FDA, the EMA expects companies to maintain a systematic and well-documented approach for identifying and addressing non-conformities, and will make it a primary focus as they audit your operation. 

 

CAPA process for pharma companies

 

What are the key steps for CAPA in pharma companies, then?

The CAPA process, regardless of industry, follows a series of standardized, repeatable steps that ensure issues are identified, resolved and prevented from recurring. 

Let's take a look at each in turn.

 

Step 1: Identification

 

The first step in the CAPA process is identification, where a problem, deviation, or nonconformity is detected.

This could come from various sources such as internal audits, customer complaints, adverse event reports, or regulatory inspections.

Once an issue is identified, it must be documented to begin the CAPA process.

Effective identification ensures that no potential issues go unnoticed.

 

Step 2: Evaluation

 

After identification, the next step is evaluation. This involves assessing the severity and scope of the issue. You’ll need to determine how widespread the problem is, its potential impact on product quality and safety, and whether immediate corrective actions are needed. A risk-based approach is often used here to prioritize issues based on their potential consequences.

The evaluation stage is critical because it helps allocate your CAPA resources efficiently, and ensures that the most serious issues are addressed first.

 

Step 3: Root cause analysis

 

In the root cause analysis step, you’ll investigate the problem in depth to uncover its underlying cause.

Simply fixing the symptoms of a problem isn't enough - identifying and addressing the root cause ensures that the issue doesn’t recur.

There are various tools you can apply to your root cause analysis, including the '5 Whys' technique or the Ishikawa 'fishbone' diagram:

 

Effective root cause analysis is a fundamental part of a successful CAPA system because it ensures long-term solutions rather than temporary fixes.

 

TOP TIP:

FDA-regulated companies often panic into action after receiving a Form 483 inspectional observation, thinking they need to get everything fixed in the 15-day response deadline that the FDA sets.

Take the time after a finding to analyze, rather than act. The FDA prefers detailed CAPA plans, underpinned by strong root cause analysis, to a series of rushed short-term fixes.

The more in-depth and thoughtful your root cause analysis, the stronger your CAPAs will be and the less chance of the issue reappearing later.

 

 

Step 4: Develop a CAPA plan

 

Once the root cause is identified, a CAPA plan is developed to implement your corrective and preventive actions.

This plan should outline the specific steps that will be taken to address the issue, including deadlines, responsible parties, and required resources. The CAPA plan should also include preventive measures to avoid similar problems in the future.

A well-thought-out CAPA plan ensures that all aspects of the issue are addressed systematically, and cascades accountability appropriately for implementing the actions.

 

Step 5: Implementation

 

After developing the plan, the next step is implementation.

This is where the corrective and preventive actions outlined in your CAPA plan are put into practice.

Implementation may involve revising procedures, retraining employees, updating equipment, or making changes to your manufacturing process.

For implementation to be successful, it’s important to monitor the progress of each action and ensure that timelines are met. Regular follow-ups can help track the progress and make adjustments if necessary.

 

Step 6: Verification of effectiveness

 

Once corrective and preventive actions are implemented, the next step is verification of effectiveness. You’ll need to assess whether the actions taken have successfully addressed the root cause and whether similar issues are unlikely to recur. This can be done through process audits, testing and ongoing monitoring.

Verification ensures that your CAPA process has achieved its intended outcome and helps maintain continuous compliance.

CAPA in pharma contexts needs to be airtight and effective for optimal patient safety - so taking the time to check your own work is key.

 

Step 7: Documentation

 

Finally, the entire CAPA process must be thoroughly documented with a CAPA report.

Documentation is a regulatory requirement and serves as evidence that you’ve taken the necessary steps to address issues and prevent future problems. FDA and EMA inspectors will scrutinize your CAPA documentation during audits.

Comprehensive documentation not only supports regulatory compliance but also helps track historical issues and improvements, contributing to better decision-making over time.

 

Best practices for CAPA implementation

 

Implementing CAPA in pharma companies successfully requires more than just following the steps above. There are a few best practices you can adopt to push the effectiveness of your CAPA system even further.

 

Cross-functional teams

 

Building cross-functional teams is essential for CAPA success. CAPA often involves various departments, from quality assurance to manufacturing and regulatory affairs. A collaborative approach ensures that different perspectives are considered when addressing issues, leading to more effective corrective and preventive actions.

Cross-functional teams can also help ensure that CAPA plans are practical and can be implemented effectively across all areas of the company.

 

 

CAPA training and education

 

Proper CAPA training and education are crucial for ensuring that everyone in the organization understands their role in the CAPA process. Employees should be trained not only on how to identify issues, but also on how to participate in root cause analysis and contribute to the implementation of CAPA plans.

Regular training keeps staff updated on CAPA requirements and best practices, fostering a collective culture of quality and compliance within the organization.

 

DOWNLOAD: Culture of quality toolkit

 

 

Continuous improvement

 

As we've seen already, CAPA in pharma companies should never be a one-time fix, but part of a broader strategy of continuous improvement.

Regularly reviewing your CAPA processes and outcomes, following the classic Plan Do Check Act model, can help identify areas for enhancement. By promoting a culture of continuous improvement, you can ensure that your company stays ahead of potential risks and remains compliant with regulatory expectations.

 

 

Managing CAPA in pharma

 

Managing CAPA effectively is essential for maintaining compliance and ensuring product quality. Implementing the right tools and systems can make this process more streamlined and efficient.

 

CAPA software for pharma companies

 

Pharmaceutical software is increasingly part and parcel of how pharma companies operate in the 21st century - and quality and compliance aren't immune to the powerful effects of digitization.

Many forward-thinking pharmaceutical companies are turning to CAPA management software to manage their corrective and preventive actions with dramatically improved efficiency.

CAPA software systems automate and accelerate your CAPA process, offering functionality such as:

• Configurable CAPA process workflows to route actions to the right personnel at the right time
• Flexible and collaborative creation processes for key documents like CAPA reports and audit forms
• Prompts and reminders to ensure actions are completed on time
• Detailed analytics to track trends, spot bottlenecks, and tackle operational problems at scale
• Automatic creation of CAPA tasks from CRM integrations: i.e. a customer complaint in Salesforce automatically triggers an investigation task for the quality manager
  
  

And more.

 

 

Using CAPA software slashes CAPA admin time by 90% or more, while eliminating the risk of manual, disconnected processes and unlocking full visibility of your CAPA landscape.

 

Benefits of an effective CAPA system in pharma

 

As you've no doubt learned already, an effective CAPA system pays dividends for your business.

CAPA in pharma companies unlocks a string of key benefits, including:

• Compliance: Meeting FDA, ICH, and EMA regulatory requirements unlocks market access and gains you new customers
• Risk management: Proactively cutting the risk of product recalls, non-compliance and safety issues insulates your company from risk and regulatory punishment
• Customer satisfaction: Continuously improving the overall quality of your products by systematically addressing issues maximizes customer happiness while minimizing churn
• Operational efficiency: Streamlining processes, reducing downtime and saving resources with targeted corrective and preventive actions makes your pharma company fitter, faster, stronger and more efficient

 

By prioritizing CAPA in your pharma company, you can ensure that your quality and compliance remain constantly in control.