FDA Guidance on Delaying, Denying, Limiting, or Refusing Drug or Device Inspection

The FDA guidance “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection” published in June 2024 outlines the behaviors and circumstances that the FDA considers to be non-compliant with inspection requirements under section 501(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). This guidance is essential for ensuring that drugs and devices are not deemed adulterated due to inspection-related issues.

The guidance aims to make sure transparency and compliance during FDA inspections to protect public health by ensuring that drugs and devices are manufactured by regulatory standards.

Legal Background

The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 added section 501(j) to the FD&C Act, which deems a drug adulterated if the owner, operator, or agent of a facility delays, denies, or limits an FDA inspection, or refuses to permit entry or inspection.

The FDA Reauthorization Act of 2017 extended these provisions to include medical devices.

Scope

The guidance applies to all facilities involved in the manufacture, processing, packing, or holding of drugs or devices. It defines what constitutes delaying, denying, limiting, or refusing an inspection, providing specific examples to illustrate these behaviors.

Examples of Non-Compliant Behaviors:

Delaying: Postponing an inspection without a reasonable explanation.
Denying: Explicitly refusing to allow an inspection to take place.
Limiting: Restricting the scope of an inspection, like limiting access to certain areas or records.
- I want to stress that this includes the situation where a facility provides some, but not all, records requested by the FDA investigator that FDA has authority to inspect. Everyone’s favorite delaying tactic.
- This also includes omitting or limiting the data contained in the electronic records when providing electronic copies of the records to FDA. This includes but is not limited to actions like removing data columns in Excel, removing data from the electronic record when providing the record to FDA, exporting data into reports without including all of the data fields (unless otherwise requested by FDA), or locking the electronic worksheet so that the data cannot be searched, sorted, or analyzed by FDA.
- Preventing an authorized representative of FDA from collecting statutorily authorized samples may be considered limiting the inspection. Examples of sample limitations include, but are not limited to, declining to allow or impeding FDA from collecting the following types of samples: environmental samples, finished product samples, raw material samples, in-process material samples, reserve samples in bioequivalence and bioanalytical studies, and labeling.
Refusing: Not allowing the FDA to enter the premises for inspection.

Background on FDA Guidance

The FDA issues guidance documents to communicate its current thinking on regulatory issues. These documents are not legally binding but give insight into how the FDA interprets and enforces laws and regulations. The guidance on delaying, denying, limiting, or refusing inspections was necessitated by the need to clearly define what constitutes non-compliance under section 501(j) of the FD&C Act. This clarity helps facilities understand their obligations and avoid actions that could lead to their products being deemed adulterated.

The guidance was finalized to replace the previous version issued in October 2014 and incorporates feedback and updates to reflect current practices and challenges in the inspection process. It is a critical tool for both the FDA and industry stakeholders to ensure that inspections are conducted smoothly and effectively, thereby safeguarding the quality and safety of drugs and devices available to the public.

Wisdom Work and the Learning Culture

The article “Why ‘Wisdom Work’ Is the New ‘Knowledge Work'” by Chip Conley at Harvard Business Review discusses the evolving dynamics in the workforce due to significant demographic shifts. As the workforce ages and younger individuals ascend to senior management roles, there is a unique opportunity for companies to harness the intergenerational transfer of wisdom. This transfer can significantly strengthen organizations by leveraging the experience and insights of older employees while integrating the innovative perspectives of younger workers. The article emphasizes that companies that successfully facilitate this exchange will enhance their overall workplace environment and performance.

This approach closely aligns with my thoughts around building expertise, and I found this a very thought provoking article.

Benefits of Wisdom Work in a Professional Setting

Enhanced Decision-Making

Wisdom work involves leveraging the collective experience and insights of employees, leading to more informed and balanced decision-making. Wise leaders consider diverse perspectives and long-term implications, which can result in more sustainable and ethical business practices.

Improved Innovation

Intergenerational knowledge transfer fosters an environment where creativity and innovation can thrive. Younger employees bring fresh ideas and familiarity with new technologies, while older employees provide context and practical wisdom. This synergy can lead to innovative solutions and improved business processes.

Increased Employee Engagement and Satisfaction

Employees who feel their knowledge and experience are valued are more likely to be engaged and motivated. Wisdom work encourages a culture of mutual respect and continuous learning, which can enhance job satisfaction and reduce turnover rates.

Better Conflict Resolution

Wisdom work promotes the development of soft skills such as empathy, communication, and problem-solving. These skills are crucial for resolving conflicts effectively and maintaining a harmonious workplace. Employees equipped with relational wisdom can navigate interpersonal challenges more smoothly, leading to a more cohesive team environment.

Enhanced Mentorship and Leadership Development

A focus on wisdom work facilitates mentorship opportunities where experienced employees guide and support younger colleagues. This not only helps in the professional development of younger employees but also keeps older employees engaged and valued. Such mentorship can accelerate the growth of leadership skills across the organization.

Adaptability and Resilience

Organizations that embrace wisdom work are better equipped to adapt to changes and uncertainties. The combined experience of older employees and the adaptability of younger ones create a resilient workforce capable of navigating complex challenges and seizing new opportunities.

Increased Productivity and Performance

The integration of wisdom work can lead to performance enhancements by leveraging the strengths of a diverse workforce. Employees can learn from each other, leading to improved productivity and business outcomes. The exchange of knowledge and skills across generations helps in creating a more competitive and efficient organization.

Fostering a Culture of Lifelong Learning

Wisdom work encourages a culture where learning and development are continuous processes. Employees are motivated to keep updating their skills and knowledge, which is essential for staying relevant in a rapidly changing business environment. This culture of lifelong learning can drive innovation and maintain a competitive edge.

I feel that the numerous benefits that wisdom work can bring to significantly enhance the professional setting really resonate with the concepts behind quality culture. By fostering intergenerational knowledge transfer, organizations can improve decision-making, innovation, employee engagement, conflict resolution, mentorship, adaptability, productivity, and create a culture of lifelong learning.

Best Ways to Address a Deviation Backlog

A deviation backlog in a regulated industry, such as pharmaceuticals, can pose significant risks to compliance, product quality, and overall operational efficiency. Addressing this backlog effectively requires a structured approach that prioritizes risk management, resource allocation, and continuous improvement.

You need to do two things first:

Prioritize Urgent Requests

Identify Critical Issues: Focus on resolving high-priority and time-sensitive deviations first to drive compliance.

Isolate and Organize

Separate Backlog from Ongoing Deviations: Create distinct queues for backlog deviations and new deviations to streamline management.
Create a Backlog Team: Assign a dedicated team to tackle the backlog, ensuring that regular support operations continue smoothly.

From there, you can then proceed into the next steps to tackle a deviation backlog:

1. Prioritize Based on Risk

Not all deviations have the same impact. Prioritizing the backlog based on the severity and risk part of each deviation is crucial. This involves:

Assessing Severity: Evaluate the potential impact of each deviation on product quality, patient safety, and regulatory compliance. Ideally you already classify deviations into categories such as minor, moderate, and major. based on those you will need to additional work to prioritize the backlog.
Risk-Based Approach: Focus on resolving high-risk deviations first to mitigate the most critical issues promptly.

2. Allocate Adequate Resources

Addressing a backlog efficiently often requires additional resources. Consider the following actions:

Increase Staffing: Temporarily augment your team with additional personnel or external consultants to handle the increased workload.
Specialized Teams: Form dedicated teams to focus solely on backlog reduction, ensuring that regular operations are not disrupted.

3. Improve and Make Robust Deviation Management Processes

A systematic approach to deviation management helps prevent backlogs from recurring. Key steps include:

Root Cause Analysis (RCA): Conduct thorough investigations to identify the underlying causes of deviations.
Corrective and Preventive Actions (CAPA): Develop and implement CAPA plans to address root causes and prevent future deviations. Ensure these plans are reviewed and approved by relevant stakeholders.

4. Regular Monitoring and Review

Continuous monitoring and regular reviews are essential to keep the backlog under control:

Track Progress: Use metrics and key performance indicators (KPIs) to monitor the progress of backlog reduction efforts. Tools like burndown charts can be helpful.
Periodic Reviews: Conduct regular review meetings to assess the status of the backlog and make necessary adjustments to the plan.

5. Enhance Deviation Management Systems

Improving your deviation management system can prevent future backlogs and streamline the resolution process:

Automation and Software Tools: Implement a eQMS or evaluate and improve the current one.
Training and Education: Ensure that all employees are well-trained in deviation management processes and understand the importance of timely reporting and resolution.

6. Foster a Culture of Continuous Improvement

Promote a culture that values continuous improvement and proactive problem-solving:

Encourage Reporting: Create an environment where employees feel comfortable reporting deviations without fear of retribution.
Learn from Deviations: Analyze deviation trends to identify areas for process improvement and implement changes to prevent recurrence.

7. Set Clear Goals and Deadlines

Establish clear goals and deadlines for backlog reduction:

Set Due Dates: Assign due dates for resolving backlog items to ensure timely action. Items that exceed their due dates should be reviewed and either expedited or reassessed for relevance.
Regular Updates: Keep all stakeholders informed about the progress and any changes to the plan through regular updates and communication.

Conclusion

Addressing a deviation backlog effectively requires a combination of prioritization, resource allocation, robust processes, continuous monitoring, and a culture of improvement. By implementing these strategies, organizations can reduce their backlog, improve compliance, and enhance overall product quality and safety.

Maybe I am Just Crazy Enough

The more I think about it, the more I am thinking I would want to organize a collaborative learning event around Validation like the one I spelled out in the article “A Collaborative Learning Event I Might Run” in June.

A Collaborative Learning Event I Might Run

So I’m hoping to pull a small team together to make an event like this happen. Any takers?

PQ and UAT

When an organization tries to unite facility, utility and equipment qualification principles of IQ, OQ, PQ to a GAMP5 driven approach for computer system validation there is often a bit of confusion about the difference between PQ and UAT. This is aggravated by the outdated IQ,OQ, and PQ that is still required by Annex 15. Add to that the fact everything is computerized these days and we get a lot of confusion.

Difference Between PQ and UAT

Performance Qualification (PQ) and User Acceptance Testing (UAT) are both crucial stages in the software validation process, but they serve different purposes and are conducted at different stages of the software development lifecycle. Here’s a detailed comparison:

Aspect	Performance Qualification (PQ)	User Acceptance Testing (UAT)
Purpose	Verifies that the system performs as expected under real-world conditions.	Confirms that the system meets the user’s needs and requirements.
Scope	Tests the system against the Functional Specification (FS).	Tests the system against the User Requirement Specification (URS).
Conducted By	Usually performed by the system developer or vendor.	Performed by the end users or their representatives.
Focus	Ensures that the system performs consistently under normal and stress conditions.	Ensures that the system provides the required functionality and usability.
Environment	Conducted in an environment that simulates the actual operational conditions.	Conducted in a controlled environment that closely resembles the production environment.
Test Basis	Based on internal processes and procedures, reflecting day-to-day or end-to-end use of the system.	Based on real or hypothetical operations to check usability and functionality.
Outcome	Provides documented evidence that the system is fit for its intended use and complies with regulations.	Provides feedback on whether the system meets user expectations and requirements.
Timing	Typically the final stage before the system is released for production use.	Conducted after the system has passed quality assurance and before final deployment.
Documentation	Test scripts derived from the Functional Specification and internal processes.	Test cases derived from the User Requirement Specification.
Regulatory Compliance	Often required to comply with regulatory standards such as 21 CFR Part 11.	Focuses on meeting the business and user requirements rather than regulatory compliance.

Key Points

Performance Qualification (PQ):
PQ tests are designed to verify that the system performs as expected under real-world conditions, ensuring it can handle normal and stress scenarios effectively.
It is typically conducted by the system developers or vendors and focuses on the system’s performance against the Functional Specification (FS).
PQ is essential for ensuring that the system is ready for production use and meets all regulatory requirements.
User Acceptance Testing (UAT):
UAT is aimed at verifying that the system meets the user’s needs and requirements, ensuring it provides the expected functionality and usability.
This testing is performed by end users or their representatives and is based on the User Requirement Specification (URS).
UAT is usually the final validation step before the software is deployed, focusing on user satisfaction and business needs.

Both PQ and UAT are integral to the software validation process, ensuring that system is both technically sound and meet user expectations. While PQ focuses on performance and regulatory compliance, UAT emphasizes user satisfaction and functional correctness.

In an upcoming post I’m going to discuss apply the needs behind these concepts within a ASTM E2500 driven approach that looks at the entire FUSE and Product validation.