Author: Jeremiah Genest

Quality professional with over 20 years of experience. Gamer and storyteller with forty years of practice.

Risk Management Addresses Uncertainty

The ICH Q9 guideline on Quality Risk Management (QRM), including its revised version ICH Q9(R1), addresses the concept of uncertainty as a critical component in risk management within the pharmaceutical industry.

Understanding Uncertainty in ICH Q9

Uncertainty in the context of ICH Q9 refers to the lack of complete knowledge about a process and its expected or unexpected variability. This uncertainty can stem from various sources, including gaps in knowledge about pharmaceutical science, process understanding, and potential failure modes.

Key Points on Uncertainty from ICH Q9(R1)

Sources of Uncertainty:

    • Knowledge Gaps: Incomplete understanding of the scientific and technical aspects of processes.
    • Process Variability: Both expected and unexpected changes in process performance.
    • Failure Modes: Unidentified or poorly understood potential points of failure in processes or systems.

    Managing Uncertainty:

      • Risk-Based Decision Making: The guideline emphasizes that decisions should be made based on the level of uncertainty, importance, and complexity of the situation. This means that more formal and structured approaches should be used when uncertainty is high.
      • Formality in QRM: ICH Q9(R1) introduces the concept of formality as a spectrum, suggesting that the degree of formality in risk management activities should be commensurate with the level of uncertainty. Less formal methods may be appropriate for well-understood processes, while highly structured methods are necessary for areas with high uncertainty.

      Reducing Subjectivity:

        • The guideline acknowledges that subjectivity can impact the effectiveness of risk management. It recommends strategies to minimize subjectivity, such as using well-recognized risk assessment tools and involving cross-functional teams to provide diverse perspectives.

        Continuous Improvement:

          • ICH Q9(R1) stresses the importance of continual improvement in risk management processes. This involves regularly updating risk assessments and control measures as new information becomes available, thereby reducing uncertainty over time.

          Practical Implementation

          In practice, managing uncertainty within the framework of ICH Q9 involves:

          • Conducting thorough risk assessments to identify potential hazards and their associated risks.
          • Applying appropriate risk control measures based on the level of uncertainty and the criticality of the process.
          • Documenting and reviewing risk management activities to ensure they remain relevant and effective as new information is obtained.

          Conclusion

          The ICH Q9 approach to uncertainty underscores the importance of a structured, knowledge-based approach to risk management in the pharmaceutical industry. By addressing uncertainty through rigorous risk assessments and appropriate control measures, organizations can enhance the reliability and safety of their processes and products, ultimately safeguarding patient health and safety.

          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.