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

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

偏差調查是任何GMP組織中重要的質量活動之一。在FDA和其他監(jiān)管機構發(fā)布的缺陷、警告信和同意令中，它們也一直處于常被引用的問題列表的首要位置。(“未能*審核[任何無法解釋的差異][批次或其任何組分不符合質量，無論批次是否已經銷售]。”)

Clearly,many organizations have room to improve in the writing and managing of deviation investigations. The following sections identify common missteps companies make when conducting deviation investigations — and how you can avoid them.

顯然，許多組織在偏差調查的編寫和管理方面仍有改進的余地。以下幾節(jié)列出了公司在進行偏差調查時所犯的常見錯誤以及如何避免這些錯誤。

1.Not leveraging historical data for continuous improvement

1.未利用歷史數(shù)據(jù)進行持續(xù)改進

The information gathered over time through investigations contains a wealth of data that can be used for continuous improvement, increasing productivity, and reducing the recurrence of investigations. Unfortunately, many organizations only review this data once a year and in a somewhat perfunctory manner. A good trending process is an important element in monitoring and proactively responding to developing issues. Tracking investigation data (root cause, functional group, unit operation) will aid in continuous monitoring of the types of events and root causes occurring in your facility by product, process area, and functional group, among others. Develop a list of standard event categories and actionable root causes in order to trend deviation and investigation data. This list can be upwards of 200 or more and can aid investigators in writing their root cause in actionable terms.

隨著時間的推移，通過調查收集到的信息包含了大量的數(shù)據(jù)，可用于不斷改進、提高生產力和減少調查的再次發(fā)生。不幸的是，許多組織每年只審查這一數(shù)據(jù)一次，而且有些敷衍了事。一個良好的趨勢過程是監(jiān)測和積極應對發(fā)展中問題的一個重要因素。跟蹤調查數(shù)據(jù)(根本原因、功能組、單元操作)將有助于持續(xù)監(jiān)控設備中按產品、流程區(qū)域和功能組等發(fā)生的事件類型和根本原因。制定標準事件類別和可采取行動的根本原因清單，以便趨勢偏差和調查數(shù)據(jù)。這份清單可以超過200或更多數(shù)據(jù)，可以幫助調查人員以可操作的方式寫出他們的根本原因。

2.Relying on human error as a root cause

2.把人為錯誤作為根本原因

This is a common finding that regulatory authorities will cite in their observations. Repeatedly stating human error as a root cause is a sign that your organization is not interested and/or resourced to find true root causes and to correct the underlying issues behind recurrence.

這是監(jiān)管當局在其缺陷中經常引用的缺陷。重復把人為錯誤作為根本原因是一個跡象，表明您的組織沒有權力和/或資源來找出真正的根本原因，并糾正重復出現(xiàn)的潛在問題。

Human error can be a root cause category, but rarely is it the true and actionable root 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 on procedure since SOP was not on training curriculum”), environment (“distraction due to false fire alarm”), or machine (“improper equipment design and layout”).

人的錯誤可以是一個根本原因類別，但它本身很少是真正的和可采取行動的根本原因。真正的根本原因通常是在其他領域，如程序(“步驟x.x不明確”)、培訓(“由于SOP沒有列入培訓課程而沒有被安排關于程序的培訓”)、環(huán)境（由于火災報警引起的注意力分散）或機器(“設備設計和布局不當”)。

It is important to find a true, underlying root cause and to describe it in actionable terms to prevent recurrence and reduce the number of future human error-related events. Such events cost the industry a staggering amount interms of lost productivity, compliance and labor costs, and the human resources needed to investigate nonconformances. The average cost of a deviation runs into tens of thousands of dollars for major pharmaceutical companies.Preventing human error recurrence not only saves organizations money, but it reduces the likelihood of compliance issues, including regulatory findings.

重要的是找到一個真正的、潛在的根源，并以可操作的方式描述它，以防止再次發(fā)生，并減少今后與人員錯誤相關的事件的數(shù)量。這類事件在生產效率損失、合規(guī)和勞動力成本以及調查不合格行為所需的人力資源等方面給企業(yè)造成了驚人的損失。對于大型制藥公司來說，偏差的平均成本高達數(shù)萬美元。防止人為錯誤的再次發(fā)生不僅節(jié)省了組織的資金，而且降低了合規(guī)問題的可能性，包括監(jiān)管缺陷。

Some quality systems will not allow human error to be used as a root cause, in order to prevent the organization from stopping short of identifying and addressing the true root cause behind errors (see error #3 below). For example, in many(but definitely not all) human error events, the employee involved could have detected the error prior to it becoming a deviation. Therefore, “in adequate ability to detect the problem” could be the actionable root cause in such situations. The resulting CAPA (corrective and preventive action) would be counseling 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 detect problems in time to prevent a deviation. Counseling just on “paying attention to detail” or on “the importance of GMPs” is not specific or adequate as a stand alone CAPA. If someone doesn’t understand the importance of GMPs, they shouldn’t be working in a GMP environment — and they definitely need more training.

一些質量系統(tǒng)不允許將人為錯誤用作根本原因，以防止組織無法識別和解決錯誤背后的真正根源(見下面的錯誤#3)。例如，在許多(但肯定不是所有)人為錯誤事件中，所涉及的員工可以在錯誤變成偏差之前檢測到錯誤。因此，在這種情況下，“發(fā)現(xiàn)問題的能力不足”是可采取行動的根本原因。由此產生的CAPA(糾正和預防行動)將是咨詢或額外培訓，重點是提高個人發(fā)現(xiàn)和解決錯誤的能力，或其他工作輔助或改進人機界面(HMI)，使操作者能夠及時更好地發(fā)現(xiàn)問題，以防止出現(xiàn)偏差。僅僅建議“注重細節(jié)”或“GMP的重要性”，作為一個獨立的CAPA來說，是不具體的，也是不夠的。如果有人不理解GMP的重要性，他們就不應該在GMP環(huán)境下工作，而且他們肯定需要更多的培訓。

3.Not getting to the probable root cause

3.沒有找到可能的根本原因

The percentage of investigations resulting in a root cause is a good metric for the health of your quality system — the higher the percentage, the better. There are many reasons why root causes are not found. Not committing adequate time and resources is one. However, it is all too common for organizations to put in sufficient effort, gather all the necessary facts and information, but still fail to identify a root cause. Sometimes, this is the direct result of the investigator’s skill — they may have been trained insufficiently or lack technical command of the issues involved.

調查出根本原因的偏差調查所占的百分比是衡量質量體系健康的一個很好的指標-這個百分比越高，越好。沒有找出根本原因的原因是多方面的，沒有投入足夠的時間和資源是其中之一。然而，更普遍的情況是作出了足夠的努力，收集所有必要的事實和信息，但仍然找不到根本原因。有時，這是調查人員技能直接導致的，他們可能沒有受過充分的培訓，或對所涉問題缺乏技術上的掌握。

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 the necessary information is available and the conclusion is readily discernable. A misguided interpretation of the facts or an unrealistic notion of definitive can 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 thorough investigation and supported by the available data and information is sufficient.

然而，令人驚訝的是，調查得出的結論也令人驚訝，即無法查明“確定的”根本原因，盡管有所有必要的資料，而且結論是顯而易見的。對事實的錯誤解釋或不現(xiàn)實的確定性概念可能會使調查無法找到最可能的根本原因。沒有任何監(jiān)管標準要求所有調查結論都是確定的。一個最可能的根本原因是以*調查為基礎并以現(xiàn)有數(shù)據(jù)和資料為依據(jù)的，這就足夠了。

The proper 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 can often tease out a challenging most probable root cause from an array of discordant facts.

對于手頭的問題，應該選擇合適的RCA(根原因分析)工具。對于更困難的調查，Kepner-Tregoe或IS-IS NOT分析通?？梢詮囊幌盗胁灰恢碌氖聦嵵姓页鼍咛魬?zhàn)性的可能的根本原因。

4.Not getting to the true root cause

4.找不到真實的根本原因

Finding the true root cause is critically important. There have been many cases where organizations failed to identify and correct the true root cause of a problem that was readily solvable — and they suffered millions of dollars in losses (or worse) as a result. The true root cause is an actionable one that is the most consistent with the available facts and information from a thorough investigation and can be the most probable root cause mentioned above.

找到真正的根源是至關重要的。在許多情況下，組織未能找出和糾正一個容易解決的問題的真正根源，結果他們遭受了數(shù)百萬美元的損失(甚至更糟)。真正的根本原因是一個可采取行動的原因，是符合現(xiàn)有的事實和*調查得出的信息，可以是最可能的根本原因，上述提到。

A true root cause is the underlying reason that allowed the event to occur.Understanding the true root cause requires the collection of all relevant facts. Sometimes, these are clearly understood at the time of the event. Othertimes, it requires in-depth technical assessments that can span several months.

真正的根本原因是允許事件發(fā)生的潛在原因。了解真正的根本原因需要收集所有相關的事實。有時，這些在事件發(fā)生時就被清楚地理解了。其他時候，它需要深入的技術評估，可以跨越幾個月。

One good test for assessing if the true root cause has been found is to see if it can be stated in terms that are directly actionable, meaning it links clearly to a corrective action and is within the organization’s control. A simple and effective way to determine if the true, actionable root cause has been found is to use the 5 Whys tool at the conclusion of an investigation, including application to the outputs from more advanced tools, such as a fishbone diagramor Kepner-Tregoe analysis.

評估是否找到了真正的根本原因一個很好的測試是，看看是否可以用直接采取行動的形式來說明，這意味著它與糾正行動有著明確的聯(lián)系且在可控制范圍內。一個簡單而有效的方法，以確定是否找到了真正的，可采取行動的根本原因是在調查結束時使用5 Whys工具，包括應用于更先進的工具，如魚骨圖或Kepner-Tregoe分析（KT法，問題解決技巧-方法）。

For example, failure of the backup power supply is not a true, actionable root cause. Why did the back-up power supply fail? Hurricane Matthew cannot be listed as an actionable root cause, because the organization cannot prevent hurricanes. However, an inadequate procedure for preventative maintenance of the backup power supply can be a true root cause, in which case the corrective action is to fix the procedure.

例如，備用電源的故障不是真正的、可采取行動的根本原因。為什么備用電源失靈？颶風馬修不能被列為可采取行動的根本原因，因為該組織無法防止颶風。然而，備用電源預防性維護程序不足可能是真正的根本原因，在這種情況下，糾正措施是完善程序。

5.Preparing an unclear or difficult-to-follow investigation report

5.準備一份不明確或難以跟進的調查報告

Many investigation writers forget that their audience is not only internal employees, but ultimately an external third-party, such as an inspector. Thus,the investigation needs to be readily understandable and clear, with all the necessary supporting facts and rationale, so that it is comprehensible years after the event. The most difficult challenge in accomplishing this is writing logically, clearly, and succinctly, without presenting and repeating redundant information. Thus, training is an important element of writing effective investigations. Having mentors available to assist investigators can be an important element in advancing skills.

許多寫調查報告的人忘記了，他們的讀者不僅是內部員工，而最終還是外部第三方，比如檢查員。因此，調查必須易于理解和清晰，包含所有必要的支持事實和理由，以便在事件發(fā)生后幾年還能理解。要做到這一點，最困難的挑戰(zhàn)是在不顯示和重復冗余信息的情況下，以邏輯、清晰和簡潔的方式書寫。因此，培訓是寫出有效調查報告的重要內容。有導師協(xié)助調查人員可能是提高技能的一個重要因素。

6. Ignoring contributing factors and associated CAPAs

6.忽視成因及相關因素

Contributing factors are elements that either were necessary — in addition to the root cause — for an event to occur, or that increased the event’s impact. Contributing factors also require root cause determinations and CAPAs. Addressing them limits the likelihood or impact of similar events recurring in the future. Too often, investigations focus only on the root cause and forget to address contributing factors. Use of the 5-Whys tool is a useful mechanism to distinguish contributing factors from root causes.

除了根本原因之外，事件發(fā)生的成因是必要的，或者是增加事件的影響的因素。成因也需要根本原因的確定和糾正預防措施。解決這些問題限制了今后再次發(fā)生類似事件的可能性或影響。調查往往只關注根本原因，而忘了處理成因。使用5-Whys工具是區(qū)分成因和根本原因的有用機制。

7. Prescribing inadequate CAPAs

7.執(zhí)行不足的糾正預防措施

Too many investigations lead to an appropriate root cause but never link that cause to a CAPA. Most root causes and contributing factors should be associated with one or more CAPAs; if not, a clearly justified rationale should be provided. One of the main purposes of an investigation is to prevent recurrence of the event, and this can only happen if the investigation determines a root cause and connects it to an appropriate,effective CAPA. Another consideration is whether or not an interim control is needed while the CAPA(s) is being implemented. A risk assessment should be used to make this determination.

太多的調查調查出了適當?shù)母驹颍珡膩頉]有將這一原因與CAPA聯(lián)系起來。大多數(shù)根本原因和促成因素應與一個或多個CAPA相關聯(lián)；如果沒有，則應提供明確的理由。調查的主要目的之一是防止事件再次發(fā)生，只有當調查確定了根本原因并將其與適當?shù)?、有效的CAPA聯(lián)系起來時，才能實現(xiàn)這種情況。另一個考慮因素是在將實施“CAPA”時是否需要臨時控制，應利用風險評估來確定。

8. Not performing interviews

8.不進行面談

Too many investigations fail to obtain information from the employees with the most relevant insight and information surrounding the event, either because the interviews are never conducted orthey occur too long after the event.

太多的調查沒有從員工那里獲得與事件相關的見解和信息，要么是因為調查從未進行，要么是在事件發(fā)生后太久才進行。

Memories fade quickly, so interviews should be conducted as soon as possible after an event occurs. Some organizations “swarm” an event immediately after it happens, with a team conducting interviews. This is called “freezing the scene.” Gathering high-quality information soon after the event will save you future time and effort, and improves the quality of the investigation.

記憶很快就會消失，所以調查應該在事件發(fā)生后盡快進行。一些組織在事件發(fā)生后立即“蜂擁而至”，由一個團隊進行面談。這就是所謂的“凍結現(xiàn)場”。事件發(fā)生后迅速收集高質量的信息將節(jié)省你今后的時間和精力，并提高調查的質量。

Talking to key personnel using well thought-out interview 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.

在適當?shù)那闆r下，用事先準備好的面談問題與關鍵人員交談，會使調查更有用、更有洞察力，調查也更有效率。面談的基本細節(jié)應在調查中加以總結。

Conclusion

結論：

While conducting a thorough deviation investigation is hard work, failing to do so will yield inaccurate root causes and misdirected CAPAs, and recurring deviations, along with increased regulatory and financial risk. The payback from investing in deviation investigations comes in the form of improved operational performance, reductionin costs, increased quality, and improved compliance.

盡管進行*的偏差調查是一項艱巨的工作，但如果不這樣做，將產生不準確的根本原因和錯誤的CAPA，以及重復的偏差，并增加監(jiān)管和經濟風險。偏差調查投入的回報來自改善運營績效，降低成本，提高質量和改善合規(guī)性。