I got a post on my RSS feed today from the FDA for a closeout letter to Safecor Health in response to the 2023 Warning Letter. Always happy to see an actual closeout letter.
The main takeaways from the FDA warning letter:
Inadequate Line Clearance and Packaging Controls:
Safecor failed to properly inspect packaging and labeling facilities before use, leading to potential mix-ups of drug products. This was evidenced by the presence of unrelated tablets and capsules during the packaging of a specific product.
The company has a history of product mix-ups, including instances where a vitamin was found in a drug meant to prevent organ transplant rejection and mislabeled blood clot prevention medication.
The firm lacked adequate procedures for cleaning and maintaining equipment, with unidentified residues found on supposedly clean equipment. This poses a risk of cross-contamination.
The company’s cleaning validation program was deemed inadequate, particularly in addressing worst-case scenarios.
Failure to Test Components:
Safecor did not adequately test incoming components, such as water used in drug manufacturing, for purity, strength, and quality.
The company relied on visual inspections without performing necessary chemical and microbiological tests.
Quality Control Unit Deficiencies:
The quality control unit failed to ensure compliance with CGMP regulations, including inadequate document control and data integrity issues.
Manufacturing records were not properly controlled, and corrections were made using correction fluid, raising concerns about data authenticity.
I get really confused on the differences between compounding pharmacies and outsourcing facilities. I’ve never worked at either, but see a lot of 483s and warning letters. So today I spent some snow day time doing some reading. I then wrote this up as a reminder to myself.
The Drug Quality and Security Act (DQSA) of 2013 introduced significant changes by distinguishing between compounding pharmacies under Section 503A and outsourcing facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA). This distinction is crucial for ensuring the safety and quality of compounded drugs.
Compounding Pharmacies (503A)
Definition and Purpose: Compounding pharmacies are licensed by state boards of pharmacy and primarily focus on creating customized medications for individual patients when commercially available drugs do not meet their needs. These pharmacies must adhere to standards set by the United States Pharmacopeia (USP), such as USP 797 for sterile compounding and USP 800 for hazardous drugs.
Regulatory Framework: Compounding pharmacies operate under the supervision of a licensed pharmacist and require a prescription for each compounded product. They are generally limited to small batches and are not allowed to engage in office-use compounding without a prescription.
Outsourcing Facilities (503B)
Definition and Purpose: Outsourcing facilities, on the other hand, are registered with the FDA and specialize in producing large batches of sterile drugs, often without the need for individual prescriptions. These facilities are designed to address drug shortages and provide complex or rarely compounded preparations to healthcare organizations.
Regulatory Framework: Unlike 503A pharmacies, 503B facilities must comply with FDA’s Current Good Manufacturing Practices (CGMP) to ensure the quality and safety of their products. They are subject to regular FDA inspections and must report on their compounded products.
Recent Regulatory Actions: The Case of ProRx, LLC
This research came about because I was reading a recent warning letter issued to ProRx, LLC, which basically stated they were failing to comply with CGMP regulations for 503B outsourcing facilities. The FDA identified serious deficiencies in sterile drug production practices, posing significant patient safety risks.
Implications for 503B Facilities
The warning letter to ProRx, LLC, serves as a reminder of the high regulatory bar set for 503B outsourcing facilities. Key implications include:
Enhanced Oversight: The FDA’s ability to inspect and enforce cGMP compliance means that 503B facilities must maintain meticulous quality control and production standards.
Patient Safety: The primary concern is ensuring that compounded drugs are safe for use. Facilities must address any deficiencies promptly to avoid recalls and protect patient health.
Partnerships and Supply Chain: The ability of 503B facilities to supply compounded drugs to healthcare organizations and pharmacies relies on their compliance with FDA regulations. Non-compliance can disrupt supply chains and impact patient access to necessary medications.
What I take away from my research is that 503B outsourcing facilities are GMP facilities, and are held to the same standard. Good to know as I evaluate their regulatory actions in the future. I think I’ve tended to dismiss them as not being in the same class of regulatory expectations.
Also, this is the second time this month where I really wonder what regulatory agencies fascination with pharmacists are in GMP facilities. Seems pretty clear to me that being a pharmacist is no indication of any capability around GMP activities.
Chang said she’s not surprised by the influence numbers have on behavioral decision-making, but what stands out to her is the robustness of the effect, which was replicated across 21 experiments involving 23,000 randomly selected participants. Despite the significant sample size, the predilection for numbers never wavered, except when numbers were presented in ways that were harder to process. Chang and her co-authors describe the mechanism underlying quantification fixation as “comparison fluency,” or the ease of judging numerical values compared with non-numbers, such as words and pictures.
Katherine Milkman, one of the coauthors, is a scholar I follow pretty closely, and this article seems pretty insightful and I’ll be reading the research this week. Our field has some difficulty here, none no more so in the mixed legacy of Deming on the subject, mostly misinterpretations if you ask me. Mark Graban wrote a great post on that last year.
In complex industries such as aviation and biotechnology, effective communication is crucial for ensuring safety, quality, and efficiency. However, the presence of communication loops and silos can significantly hinder these efforts. The concept of the “Tower of Babel” problem, as explored in the aviation sector by Follet, Lasa, and Mieusset in HS36, highlights how different professional groups develop their own languages and operate within isolated loops, leading to misunderstandings and disconnections. This article has really got me thinking about similar issues in my own industry.
The Tower of Babel Problem: A Thought-Provoking Perspective
The HS36 article provides a thought-provoking perspective on the “Tower of Babel” problem, where each aviation professional feels in control of their work but operates within their own loop. This phenomenon is reminiscent of the biblical story where a common language becomes fragmented, causing confusion and separation among people. In modern industries, this translates into different groups using their own jargon and working in isolation, making it difficult for them to understand each other’s perspectives and challenges.
For instance, in aviation, air traffic controllers (ATCOs), pilots, and managers each have their own “loop,” believing they are in control of their work. However, when these loops are disconnected, it can lead to miscommunication, especially when each group uses different terminology and operates under different assumptions about how work should be done (work-as-prescribed vs. work-as-done). This issue is equally pertinent in the biotech industry, where scientists, quality assurance teams, and regulatory affairs specialists often work in silos, which can impede the development and approval of new products.
Tower of Babel by Joos de Momper, Old Masters Museum
Impact on Decision Making
Decision making in biotech is heavily influenced by Good Practice (GxP) guidelines, which emphasize quality, safety, and compliance – and I often find that the aviation industry, as a fellow highly regulated industry, is a great place to draw perspective.
When communication loops are disconnected, decisions may not fully consider all relevant perspectives. For example, in GMP (Good Manufacturing Practice) environments, quality control teams might focus on compliance with regulatory standards, while research and development teams prioritize innovation and efficiency. If these groups do not effectively communicate, decisions might overlook critical aspects, such as the practicality of implementing new manufacturing processes or the impact on product quality.
Furthermore, ICH Q9(R1) guideline emphasizes the importance of reducing subjectivity in Quality Risk Management (QRM) processes. Subjectivity can arise from personal opinions, biases, or inconsistent interpretations of risks by stakeholders, impacting every stage of QRM. To combat this, organizations must adopt structured approaches that prioritize scientific knowledge and data-driven decision-making. Effective knowledge management is crucial in this context, as it involves systematically capturing, organizing, and applying internal and external knowledge to inform QRM activities.
Academic Research on Communication Loops
Research in organizational behavior and communication highlights the importance of bridging these silos. Studies have shown that informal interactions and social events can significantly improve relationships and understanding among different professional groups (Katz & Fodor, 1963). In the biotech industry, fostering a culture of open communication can help ensure that GxP decisions are well-rounded and effective.
Moreover, the concept of “work-as-done” versus “work-as-prescribed” is relevant in biotech as well. Operators may adapt procedures to fit practical realities, which can lead to discrepancies between intended and actual practices. This gap can be bridged by encouraging feedback and continuous improvement processes, ensuring that decisions reflect both regulatory compliance and operational feasibility.
Case Studies and Examples
Aviation Example: The HS36 article provides a compelling example of how disconnected loops can hinder effective decision making in aviation. For instance, when a standardized phraseology was introduced, frontline operators felt that this change did not account for their operational needs, leading to resistance and potential safety issues. This illustrates how disconnected loops can hinder effective decision making.
Product Development: In the development of a new biopharmaceutical, different teams might have varying priorities. If the quality assurance team focuses solely on regulatory compliance without fully understanding the manufacturing challenges faced by production teams, this could lead to delays or quality issues. By fostering cross-functional communication, these teams can align their efforts to ensure both compliance and operational efficiency.
ICH Q9(R1) Example: The revised ICH Q9(R1) guideline emphasizes the need to manage and minimize subjectivity in QRM. For instance, in assessing the risk of a new manufacturing process, a structured approach using historical data and scientific evidence can help reduce subjective biases. This ensures that decisions are based on comprehensive data rather than personal opinions.
Technology Deployment: . A recent FDA Warning Letter to Sanofi highlighted the importance of timely technological upgrades to equipment and facility infrastructure. This emphasizes that staying current with technological advancements is essential for maintaining regulatory compliance and ensuring product quality. However the individual loops of decision making amongst the development teams, operations and quality can lead to major mis-steps.
To overcome the challenges posed by communication loops and silos, organizations can implement several strategies:
Promote Cross-Functional Training: Encourage professionals to explore other roles and challenges within their organization. This can help build empathy and understanding across different departments.
Foster Informal Interactions: Organize social events and informal meetings where professionals from different backgrounds can share experiences and perspectives. This can help bridge gaps between silos and improve overall communication.
Define Core Knowledge: Establish a minimum level of core knowledge that all stakeholders should possess. This can help ensure that everyone has a basic understanding of each other’s roles and challenges.
Implement Feedback Loops: Encourage continuous feedback and improvement processes. This allows organizations to adapt procedures to better reflect both regulatory requirements and operational realities.
Leverage Knowledge Management: Implement robust knowledge management systems to reduce subjectivity in decision-making processes. This involves capturing, organizing, and applying internal and external knowledge to inform QRM activities.
Combating Subjectivity in Decision Making
In addition to bridging communication loops, reducing subjectivity in decision making is crucial for ensuring quality and safety. The revised ICH Q9(R1) guideline provides several strategies for this:
Structured Approaches: Use structured risk assessment tools and methodologies to minimize personal biases and ensure that decisions are based on scientific evidence.
Data-Driven Decision Making: Prioritize data-driven decision making by leveraging historical data and real-time information to assess risks and opportunities.
Cognitive Bias Awareness: Train stakeholders to recognize and mitigate cognitive biases that can influence risk assessments and decision-making processes.
Conclusion
In complex industries effective communication is essential for ensuring safety, quality, and efficiency. The presence of communication loops and silos can lead to misunderstandings and poor decision making. By promoting cross-functional understanding, fostering informal interactions, and implementing feedback mechanisms, organizations can bridge these gaps and improve overall performance. Additionally, reducing subjectivity in decision making through structured approaches and data-driven decision making is critical for ensuring compliance with GxP guidelines and maintaining product quality. As industries continue to evolve, addressing these communication challenges will be crucial for achieving success in an increasingly interconnected world.
Katz, D., & Fodor, J. (1963). The Structure of a Semantic Theory. Language, 39(2), 170–210.
Dekker, S. W. A. (2014). The Field Guide to Understanding Human Error. Ashgate Publishing.
Shorrock, S. (2023). Editorial. Who are we to judge? From work-as-done to work-as-judged. HindSight, 35, Just Culture…Revisited. Brussels: EUROCONTROL.
Great thought piece on the use of “reputation” in purpose statement, which should include quality policies.
Writing a quality policy is a crucial step in establishing a quality management system within an organization. Here are some best practices to consider when crafting an effective quality policy:
Key Components of a Quality Policy
Management’s Quality Commitment
The Quality Policy reflects top management’s dedication to quality standards. It includes clear quality objectives, resource allocation, regular policy reviews, active participation in quality initiatives, and support for quality-focused training. The quality policy is a lynchpin artifact to quality culture.
Customer-Centric Approach
Identify customer requirements.
Meet customer expectations.
Handle customer feedback.
Improve customer satisfaction.
Track customer experience metrics
Drive for Continuous Improvement
Regularly evaluate process effectiveness, product quality metrics, service delivery standards, employee performance, and quality management systems. Document specific improvement methods and set measurable targets.
Steps to Write a Quality Policy
Define the Quality Vision
Develop a concise and inspiring statement that describes what quality means to your organization and how it supports your mission and values.
Identify Quality Objectives
Align these objectives with your strategic goals and customer needs.
Develop the Quality Policy
Focus on clear, actionable statements that reflect your organization’s quality commitments. Include specific quality objectives, measurement criteria, and implementation strategies.
Communicate the Quality Policy
Ensure all employees understand the policy and their roles in implementing it. Use various channels such as publishing on the company website or displaying in premises.
Implement and Review:
Create a structured implementation timeline with clear milestones. Establish communication channels for ongoing feedback and questions. Make sure employees at all levels are involved. Regularly review and refine the policy to ensure it remains relevant and effective.
Additional Best Practices
Keep it Simple and Relevant: Ensure the policy is easy to understand and aligns with your organization’s strategic direction.
Top Management Involvement: Top management should actively participate in creating and endorsing the policy to demonstrate leadership commitment.
ISO Compliance: If applicable, ensure the policy meets ISO standards such as ISO 9001:2015, which requires the policy to be documented, communicated, and enforced by top management.
By following these guidelines, you can create a quality policy that effectively guides your organization towards achieving its quality goals and maintaining a culture of excellence.
Investigations of a Dog 