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发表于:2019-10-10 浏览:3122


By James Blackwell, Ph.D., The Windshire Group, LLC

  Deviationinvestigations are one of the most important quality activities in any GMP(good manufacturing practice) organization. They are also perennially near thetop of the list of most frequently cited issues in observations, warningletters, and consent decrees from the U.S. Food and Drug Administration (FDA)and other regulatory authorities.1 (“There is a failure to thoroughly review [any unexplained discrepancy][the failure of a batch or any of its components to meet any of itsspecifications] whether or not the batch has been already distributed.”)


  Clearly,many organizations have room to improve in the writing and managing ofdeviation investigations. The following sections identify common misstepscompanies make when conducting deviation investigations — and how you can avoidthem.


  1.Not leveraging historical data for continuous improvementTheinformation gathered over time through investigations contains a wealth of datathat can be used for continuous improvement, increasing productivity, andreducing the recurrence of investigations. Unfortunately, many organizationsonly review this data once a year and in a somewhat perfunctory manner.Agood trending process is an important element in monitoring and proactivelyresponding to developing issues. Tracking investigation data (root cause,functional group, unit operation) will aid in continuous monitoring of thetypes of events and root causes occurring in your facility by product, processarea, and functional group, among others.Developa list of standard event categories and actionable root causes in order totrend deviation and investigation data. This list can be upwards of 200 or moreand can aid investigators in writing their root cause in actionable terms.




  2.Relying on human error as a root causeThisis a common finding that regulatory authorities will cite in theirobservations. Repeatedly stating human error as a root cause is a sign thatyour organization is not interested and/or resourced to find true root causesand to correct the underlying issues behind recurrence.Humanerror can be a root cause category, but rarely is it the true and actionableroot cause, in and of itself. The true root cause is usually in other areas,such as procedures (“step x.x unclear”), training (“wasn’t assigned training onprocedure since SOP was not on training curriculum”), environment (“distractiondue to false fire alarm”), or machine (“improper equipment design and layout”).Itis important to find a true, underlying root cause and to describe it inactionable terms to prevent recurrence and reduce the number of future humanerror-related events. Such events cost the industry a staggering amount interms of lost productivity, compliance and labor costs, and the human resourcesneeded to investigate nonconformances. The average cost of a deviation runsinto tens of thousands of dollars for major pharmaceutical companies.Preventing human error recurrence not only saves organizations money, but itreduces the likelihood of compliance issues, including regulatory findings.Somequality systems will not allow human error to be used as a root cause, in orderto prevent the organization from stopping short of identifying and addressingthe true root cause behind errors (see error #3 below). For example, in many(but definitely not all) human error events, the employee involved could havedetected the error prior to it becoming a deviation. Therefore, “inadequateability to detect the problem” could be the actionable root cause in suchsituations. The resulting CAPA (corrective and preventive action) would becounseling or additional training that focuses on increasing the person’sability to detect and fix an error, or other job aids or improvements in theHMI (human machine interface) that will allow operators to better detectproblems in time to prevent a deviation. Counseling just on “paying attentionto detail” or on “the importance of GMPs” is not specific or adequate as astandalone CAPA. If someone doesn’t understand the importance of GMPs, theyshouldn’t be working in a GMP environment — and they definitely need moretraining.




  3.Not getting to the probable root causeThepercentage of investigations resulting in a root cause is a good metric for thehealth of your quality system — the higher the percentage, the better. Thereare many reasons why root causes are not found. Not committing adequate timeand resources is one. However, it is all too common for organizations to put insufficient effort, gather all the necessary facts and information, but stillfail to identify a root cause. Sometimes, this is the direct result of theinvestigator’s skill — they may have been trained insufficiently or lacktechnical command of the issues involved.However,it is also surprisingly common for an investigation to conclude that a“definitive” root cause could not be identified, despite the fact that all thenecessary information is available and the conclusion is readily discernable. Amisguided interpretation of the facts or an unrealistic notion of definitivecan prevent the investigation from arriving at a most probable root cause.There is no regulatory standard that requires all investigation conclusions bedefinitive. A most probable root cause based on and justified by a thoroughinvestigation and supported by the available data and information issufficient.Theproper RCA (root cause analysis) tool should be chosen for the problem at hand.For more difficult investigations, a Kepner-Tregoe or IS-IS NOT analysis canoften tease out a challenging most probable root cause from an array ofdiscordant facts.



  4.Not getting to the true root causeFindingthe true root cause is critically important. There have been many cases whereorganizations failed to identify and correct the true root cause of a problemthat was readily solvable — and they suffered millions of dollars in losses (orworse) as a result. The true root cause is an actionable one that is the mostconsistent with the available facts and information from a thoroughinvestigation and can be the most probable root cause mentioned above.Atrue root cause is the underlying reason that allowed the event to occur.Understanding the true root cause requires the collection of all relevantfacts. Sometimes, these are clearly understood at the time of the event. Othertimes, it requires in-depth technical assessments that can span several months.Onegood test for assessing if the true root cause has been found is to see if itcan be stated in terms that are directly actionable, meaning it links clearlyto a corrective action and is within the organization’s control. A simple andeffective way to determine if the true, actionable root cause has been found isto use the 5 Whys tool at the conclusion of an investigation, includingapplication to the outputs from more advanced tools, such as a fishbone diagramor Kepner-Tregoe analysis.Forexample, failure of the backup power supply is not a true, actionable rootcause. Why did the back-up power supply fail? Hurricane Matthew cannot belisted as an actionable root cause, because the organization cannot preventhurricanes. However, an inadequate procedure for preventative maintenance ofthe backup power supply can be a true root cause, in which case the correctiveaction is to fix the procedure.



  找到真正的根源是至关重要的。在许多情况下,组织未能找出和纠正一个容易解决的问题的真正根源-结果他们遭受了数百万美元的损失(甚至更糟)。真正的根本原因是一个可采取行动的原因,这是最符合现有的事实和资料,从一个彻底的调查,可以是最可能的根本原因,上述提到。真正的根本原因是允许事件发生的根本原因。了解真正的根本原因需要收集所有相关的事实。有时,这些在事件发生时就被清楚地理解了。其他时候,它需要深入的技术评估,可以跨越几个月.评估是否找到了真正的根本原因的一个很好的测试是,看看是否可以用可以直接采取行动的术语来说明这一问题,这意味着它与纠正行动有着明确的联系,属于组织的控制范围。一个简单而有效的方法,以确定是否找到了真正的,可采取行动的根本原因是使用5 Whys工具在调查结束,包括应用于更先进的工具,如鱼骨图或Kepner-Tregoe分析(KT法,问题解决技巧-方法)。例如,备份电源的故障不是真正的、可采取行动的根本原因。为什么备用电源失灵?飓风马修不能被列为可采取行动的根本原因,因为该组织无法防止飓风。然而,后备电源预防性维护程序不足可能是真正的根本原因,在这种情况下,纠正措施是修复程序。

  5.Preparing an unclear or difficult-to-follow investigation reportManyinvestigation writers forget that their audience is not only internalemployees, but ultimately an external third-party, such as an inspector. Thus,the investigation needs to be readily understandable and clear, with all thenecessary supporting facts and rationale, so that it is comprehensible yearsafter the event. The most difficult challenge in accomplishing this is writinglogically, clearly, and succinctly, without presenting and repeating redundantinformation. Thus, training is an important element of writing effectiveinvestigations. Having mentors available to assist investigators can be animportant element in advancing skills.



  6. Ignoring contributing factors and associatedCAPAsContributing factors are elements that eitherwere necessary — in addition to the root cause — for an event to occur, or thatincreased the event’s impact. Contributing factors also require root causedeterminations and CAPAs. Addressing them limits the likelihood or impact ofsimilar events recurring in the future. Too often, investigations focus only onthe root cause and forget to address contributing factors. Use of the 5-Whystool is a useful mechanism to distinguish contributing factors from rootcauses.



  7. Prescribing inadequate CAPAsToo many investigations lead to an appropriateroot cause but never link that cause to a CAPA. Most root causes andcontributing factors should be associated with one or more CAPAs; if not, aclearly justified rationale should be provided. One of the main purposes of aninvestigation is to prevent recurrence of the event, and this can only happenif the investigation determines a root cause and connects it to an appropriate,effective CAPA. Another consideration is whether or not an interim control isneeded while the CAPA(s) is being implemented. A risk assessment should be usedto make this determination.




  8. Not performing interviewsToo many investigations fail to obtaininformation from the employees with the most relevant insight and informationsurrounding the event, either because the interviews are never conducted orthey occur too long after the event. Memories fade quickly, so interviewsshould be conducted as soon as possible after an event occurs. Someorganizations “swarm” an event immediately after it happens, with a teamconducting interviews. This is called “freezing the scene.” Gatheringhigh-quality information soon after the event will save you future time andeffort, and improves the quality of the investigation.Talking to key personnel using well thought-outinterview questions prepared in advance, when applicable, will make theinterview more useful and insightful and the investigation much more efficient.The essential details of interviews should be summarized in the investigation.



  ConclusionWhile conducting a thorough deviationinvestigation is hard work, failing to do so will yield inaccurate root causesand misdirected CAPAs, and recurring deviations, along with increasedregulatory and financial risk. The payback from investing in deviationinvestigations comes in the form of improved operational performance, reductionin costs, increased quality, and improved compliance.



  References:FDAFY 2015 Inspectional Observation Summaries: http://www.fda.gov/ICECI/Inspections/ucm481432.htm#Drugs

  文章来源: 新药研发质量管理



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