“If a factory is torn down, but the rationality that produced it is left standing, then that rationality will simply produce another factory.” Robert Pirsig, Zen and the art of motorcycle managementWarning letters and their impactAn analysis of the number of warning letters issued by USFDA over the years [1] to pharmaceutical companies across the globe has been increasing over the years.<figure class="image"><img style="aspect-ratio:16668/11669;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-1-01_1733242587.jpg" width="16668" height="11669"></figure>In the warning letter, the FDA makes it clear that the concerned company must correct the problem and provide directions and a timeframe for the company to inform the FDA of their plans for correction. Failure to address the FDA’s concerns can lead to enforcement actions that have significant repercussions as well as product liability exposure. Therefore when a warning letter is received, company employees, especially senior management (who are already very busy), scramble to address it within the stipulated time frame.It is estimated that a single warning letter leads to a loss of approx. 900 man-hours across the hierarchy. This increases exponentially if multiple warning letters are received simultaneously. It has to be noted that this will be at the cost of progress on their routine, ongoing tasks.&nbsp;<figure class="image"><img style="aspect-ratio:16668/10032;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-2-01_1733242600.jpg" width="16668" height="10032"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Estimation-of-time-needed-to-address-a-single-warning-letter.png" alt="">After this marathon, the remediation procedures that FDA expects companies to implement can be even more expensive than complying in the first place. Moreover, there are long-term repercussions in terms losing credibility with regulators - not just the FDA but also other global regulators, leading to increased scrutiny and more inspections. In case of repeat offenders, they often have to pay hefty fines and sign a consent decree of permanent injunction that will bind them to be compliant in perpetuity. All this can impact the company’s business/financial performance, affect company valuations, and reduce the overall reputation.&nbsp;The problemThe major reasons for FDA warning letters are not unknown. About 50% of FDA warning letters pinpoint CAPA (Corrective Action and Preventive Action) failures [2]. CAPA failures also show up year after year in these warning letters. The FDA also clearly indicates FDA that most of these CAPA failures are a failure of root cause analysis.&nbsp;<figure class="image"><img style="aspect-ratio:16668/8279;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-3-01_1733242664.jpg" width="16668" height="8279"></figure>What does not work well?&nbsp;So, over the years, pharma labs have used multiple techniques to identify the root cause so that they can take the necessary actions to improve their quality performance. The popular techniques employed include 5-Whys, Fishbone diagrams, Pareto charts, Failure Mode and Effect Analysis (FMEA), decision trees, and brainstorming.&nbsp;A significant chunk of the results of these analyses tends to point to human or analyst error (~40-55%). Therefore, some of the typical actions companies have taken are adopting digital systems to reduce documentation error, putting in next-generation analytical testing technology, automating a of few of the quality processes, increasing the level of supervision in the lab, increasing the training of analysts and addition of resources to reduce the load on the system.&nbsp;<figure class="image"><img style="aspect-ratio:16668/12347;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-4-01_1733242679.jpg" width="16668" height="12347"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Typical-results-of-analysis-of-sources-of-error.png" alt="">However, experience has shown many of these companies that these steps (always quite expensive in terms of time or money or both), while offering some improvement, do not help sustain high-quality standards consistently. After a while, any improvement that accrued stagnates, or even more perplexingly, when something improves, something else seems to deteriorate. Moreover, FDA has increasingly been criticizing the finding of ‘human error’ as the conclusion of root cause analysis as limited or shallow and has been urging companies to take a deeper look.&nbsp;<figure class="image"><img style="aspect-ratio:16668/10100;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-5-01_1733242692.jpg" width="16668" height="10100"></figure><h5>The real root cause: Cognitive overload</h5><figure class="image"><img style="aspect-ratio:16668/6058;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-6-01_1733242720.jpg" width="16668" height="6058"></figure>A closer study of the testing environment in pharma companies will indicate that the analysts are often under a situation of significant ‘Cognitive Overload’. The analysts have the responsibility to<ul><li>conduct all activities of assigned tests as per the TDS (Test Data Sheet) - i.e. collect glassware and documents, arrange for chemicals and reagents, ensure the validity of all solutions prepared till tests are complete, select appropriate equipment (e.g., column), manage instruments, etc.&nbsp;</li><li>generate an audit trail for which they also have to record the equipment used.&nbsp;</li><li>concurrently record various observations in TDS and maintain a separate checklist to ensure no steps are missed.&nbsp;</li></ul>Skips and misses: All this the analysts have to manage in an eight-hour shift by switching between various stages of testing (instrument setting/monitoring, solution preparation, mobile phase, collecting glassware, checking/arranging resources, etc.) and by trying to take advantage of the natural waiting time in some of these stages. Unfortunately, the human brain finds such a balancing act and this level of multi-tasking very difficult to manage. Therefore, occurrences of inadvertent skips and misses became inevitable.Systemic error masked as human error: In addition to such human errors, testing environments also tend to have systemic errors due to<ul><li>missing information in the SOPs set or because of inadequately documented SOPs.</li><li>a process gap or due to a gap in the testing method</li></ul>However, when faced with a melee of different kinds of problems cropping up daily, it is difficult for managers to correctly infer and assign real causality for these errors. So, in this confusion, even systemic errors are mistaken for human error. This inevitably leads to frequent-finger pointing, stress and inability to take timely corrective actions.<figure class="image"><img style="aspect-ratio:16668/11569;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-7-01_1733242736.jpg" width="16668" height="11569"></figure>Direction of solution:Based on these insights, it is obvious that the only option is to first address the cognitive overload in the system to bring down real manual errors to minimal levels. Then, the systemic errors due to incorrect methods followed, unclear procedures, etc., will become visible, and actions can be taken to rectify them.&nbsp;While this logic is unrefutably simple, implementing a system-wide, counterintuitive solution that can significantly reduce the cognitive load on analysts without sacrificing overall productivity is obviously a huge challenge. The key to this is to release capacity by identifying and eliminating significant wastages in the analyst’s activities. Research by Vector has shown that the level of analyst capacity wastage can be as high as 40% in a typical pharma lab.&nbsp;<figure class="image"><img style="aspect-ratio:16668/18428;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-8-01_1733242750.jpg" width="16668" height="18428"></figure>The ‘flow’ focussed solution that Vector implements to eliminate these wastages and for release capacity serve a dual purpose. On the one hand it enables the released capacity to be used for controlling the loading of analysts, and on the other, it will reset the company’s quality practices to a much higher level of rigour. For instance, improving the STPs (Standard Testing Procedures) by detailing them more thoroughly to remove elements of subjectivity can ensure that a large number of systematic errors are eliminated.&nbsp;<figure class="image"><img style="aspect-ratio:16668/11764;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-9-01_1733242761.jpg" width="16668" height="11764"></figure>A few pioneering companies have implemented this new approach. Within a few months, they could significantly reduce invalid OOS and bring down lab incidents! Some salient details of the results of the implementation achieved with a major multi-national pharma company’s labs in a year are as below:&nbsp;<figure class="image"><img style="aspect-ratio:16668/9607;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-10-01_1733242775.jpg" width="16668" height="9607"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Parameter-and-improvement.png" alt="">If more companies address cognitive overload, which is the true root cause of their quality issues, it can bring down quality-related inconsistencies and keep companies ‘inspection ready’ at all times. With that, one is sure to see a dramatic dip in the warning letters the FDA has to issue.&nbsp;

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Many generic pharma companies continue to struggle with high levels of invalid OOS and lab incidents, making them vulnerable to adverse observations from the US FDA. Often, 'analyst error' is cited as the reason, but the real reason is something else.

Getting to the true root of lab quality problems

“If a factory is torn down, but the rationality that produced it is left standing, then that rationality will simply produce another factory.” Robert Pirsig, Zen and the art of motorcycle managementWarning letters and their impactAn analysis of the number of warning letters issued by USFDA over the years [1] to pharmaceutical companies across the globe has been increasing over the years.<figure class="image"><img style="aspect-ratio:16668/11669;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-1-01_1733242587.jpg" width="16668" height="11669"></figure>In the warning letter, the FDA makes it clear that the concerned company must correct the problem and provide directions and a timeframe for the company to inform the FDA of their plans for correction. Failure to address the FDA’s concerns can lead to enforcement actions that have significant repercussions as well as product liability exposure. Therefore when a warning letter is received, company employees, especially senior management (who are already very busy), scramble to address it within the stipulated time frame.It is estimated that a single warning letter leads to a loss of approx. 900 man-hours across the hierarchy. This increases exponentially if multiple warning letters are received simultaneously. It has to be noted that this will be at the cost of progress on their routine, ongoing tasks.&nbsp;<figure class="image"><img style="aspect-ratio:16668/10032;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-2-01_1733242600.jpg" width="16668" height="10032"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Estimation-of-time-needed-to-address-a-single-warning-letter.png" alt="">After this marathon, the remediation procedures that FDA expects companies to implement can be even more expensive than complying in the first place. Moreover, there are long-term repercussions in terms losing credibility with regulators - not just the FDA but also other global regulators, leading to increased scrutiny and more inspections. In case of repeat offenders, they often have to pay hefty fines and sign a consent decree of permanent injunction that will bind them to be compliant in perpetuity. All this can impact the company’s business/financial performance, affect company valuations, and reduce the overall reputation.&nbsp;The problemThe major reasons for FDA warning letters are not unknown. About 50% of FDA warning letters pinpoint CAPA (Corrective Action and Preventive Action) failures [2]. CAPA failures also show up year after year in these warning letters. The FDA also clearly indicates FDA that most of these CAPA failures are a failure of root cause analysis.&nbsp;<figure class="image"><img style="aspect-ratio:16668/8279;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-3-01_1733242664.jpg" width="16668" height="8279"></figure>What does not work well?&nbsp;So, over the years, pharma labs have used multiple techniques to identify the root cause so that they can take the necessary actions to improve their quality performance. The popular techniques employed include 5-Whys, Fishbone diagrams, Pareto charts, Failure Mode and Effect Analysis (FMEA), decision trees, and brainstorming.&nbsp;A significant chunk of the results of these analyses tends to point to human or analyst error (~40-55%). Therefore, some of the typical actions companies have taken are adopting digital systems to reduce documentation error, putting in next-generation analytical testing technology, automating a of few of the quality processes, increasing the level of supervision in the lab, increasing the training of analysts and addition of resources to reduce the load on the system.&nbsp;<figure class="image"><img style="aspect-ratio:16668/12347;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-4-01_1733242679.jpg" width="16668" height="12347"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Typical-results-of-analysis-of-sources-of-error.png" alt="">However, experience has shown many of these companies that these steps (always quite expensive in terms of time or money or both), while offering some improvement, do not help sustain high-quality standards consistently. After a while, any improvement that accrued stagnates, or even more perplexingly, when something improves, something else seems to deteriorate. Moreover, FDA has increasingly been criticizing the finding of ‘human error’ as the conclusion of root cause analysis as limited or shallow and has been urging companies to take a deeper look.&nbsp;<figure class="image"><img style="aspect-ratio:16668/10100;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-5-01_1733242692.jpg" width="16668" height="10100"></figure><h5>The real root cause: Cognitive overload</h5><figure class="image"><img style="aspect-ratio:16668/6058;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-6-01_1733242720.jpg" width="16668" height="6058"></figure>A closer study of the testing environment in pharma companies will indicate that the analysts are often under a situation of significant ‘Cognitive Overload’. The analysts have the responsibility to<ul><li>conduct all activities of assigned tests as per the TDS (Test Data Sheet) - i.e. collect glassware and documents, arrange for chemicals and reagents, ensure the validity of all solutions prepared till tests are complete, select appropriate equipment (e.g., column), manage instruments, etc.&nbsp;</li><li>generate an audit trail for which they also have to record the equipment used.&nbsp;</li><li>concurrently record various observations in TDS and maintain a separate checklist to ensure no steps are missed.&nbsp;</li></ul>Skips and misses: All this the analysts have to manage in an eight-hour shift by switching between various stages of testing (instrument setting/monitoring, solution preparation, mobile phase, collecting glassware, checking/arranging resources, etc.) and by trying to take advantage of the natural waiting time in some of these stages. Unfortunately, the human brain finds such a balancing act and this level of multi-tasking very difficult to manage. Therefore, occurrences of inadvertent skips and misses became inevitable.Systemic error masked as human error: In addition to such human errors, testing environments also tend to have systemic errors due to<ul><li>missing information in the SOPs set or because of inadequately documented SOPs.</li><li>a process gap or due to a gap in the testing method</li></ul>However, when faced with a melee of different kinds of problems cropping up daily, it is difficult for managers to correctly infer and assign real causality for these errors. So, in this confusion, even systemic errors are mistaken for human error. This inevitably leads to frequent-finger pointing, stress and inability to take timely corrective actions.<figure class="image"><img style="aspect-ratio:16668/11569;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-7-01_1733242736.jpg" width="16668" height="11569"></figure>Direction of solution:Based on these insights, it is obvious that the only option is to first address the cognitive overload in the system to bring down real manual errors to minimal levels. Then, the systemic errors due to incorrect methods followed, unclear procedures, etc., will become visible, and actions can be taken to rectify them.&nbsp;While this logic is unrefutably simple, implementing a system-wide, counterintuitive solution that can significantly reduce the cognitive load on analysts without sacrificing overall productivity is obviously a huge challenge. The key to this is to release capacity by identifying and eliminating significant wastages in the analyst’s activities. Research by Vector has shown that the level of analyst capacity wastage can be as high as 40% in a typical pharma lab.&nbsp;<figure class="image"><img style="aspect-ratio:16668/18428;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-8-01_1733242750.jpg" width="16668" height="18428"></figure>The ‘flow’ focussed solution that Vector implements to eliminate these wastages and for release capacity serve a dual purpose. On the one hand it enables the released capacity to be used for controlling the loading of analysts, and on the other, it will reset the company’s quality practices to a much higher level of rigour. For instance, improving the STPs (Standard Testing Procedures) by detailing them more thoroughly to remove elements of subjectivity can ensure that a large number of systematic errors are eliminated.&nbsp;<figure class="image"><img style="aspect-ratio:16668/11764;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-9-01_1733242761.jpg" width="16668" height="11764"></figure>A few pioneering companies have implemented this new approach. Within a few months, they could significantly reduce invalid OOS and bring down lab incidents! Some salient details of the results of the implementation achieved with a major multi-national pharma company’s labs in a year are as below:&nbsp;<figure class="image"><img style="aspect-ratio:16668/9607;" src="https://backend.vectorconsulting.in/storage/editor_uploads//ls-article-1-img-10-01_1733242775.jpg" width="16668" height="9607"></figure><img src="https://qclab.app/wp-content/uploads/2023/06/Parameter-and-improvement.png" alt="">If more companies address cognitive overload, which is the true root cause of their quality issues, it can bring down quality-related inconsistencies and keep companies ‘inspection ready’ at all times. With that, one is sure to see a dramatic dip in the warning letters the FDA has to issue.&nbsp;&nbsp;

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Explore how addressing cognitive overload in pharma labs can resolve quality issues and reduce FDA warning letters. Learn about innovative solutions and real-world results.

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