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Handling of Microbiological Data Deviation in MicrobiologyLaboratory
微生物实验室微生物数据偏离处理SOP
Objective:
目的
To lay down the procedure for Handling of MicrobiologicalData Deviation in Microbiology Laboratory.
制定微生物实验室微生物数据偏离处理程序。
Scope:
范围
This procedure is applicable to environmental monitoringexcursions (namely Passive air sampling, Active air sampling, Surface sampling,Personnel monitoring, and Compressed gas monitoring)obtained during theEnvironmental monitoring, Sterility testing, Bacterial Endotoxin Test,Bioburden, Microbial Limit test, Liquid borne particulate matter test,AET, CC-integrity tests and Water Samples.
本程序适用于环境监测（即沉降菌、浮游菌、表面微生物、人员监测和压缩空气监测）、无菌检测、细菌内毒素检测、生物负载、微生物限度检测、液体颗粒检测、AET、CC完整性测试和水样检测。
Responsibility:
职责
Microbiologist is responsible for implementation of theprocedure and to report and carry out primary investigation.
微生物检验人员负责执行该程序，并报告和进行初步调查。
Head Microbiology/Designee – Carryout investigation inmicrobiology section and ensure overall compliance of the SOP.
微生物主任：对微生物部分进行调查，并确保遵循SOP。
QA Executive/Designee -To assign the Microbiological datadeviation (MDD) Number as per standard operating procedures.
QA主管：根据标准操作程序发放微生物数据偏离（MDD）编号。
IPQA Executive/Designee – To carryout the investigation inmanufacturing area.
现场QA主管：对生产领域进行调查。
Head production/designee -To support the investigation inmanufacturing area.
生产部长：配合生产领域的调查。
Head Engineering /designee -To carryout the investigationin engineering related area.
工程部长：对工程相关领域进行调查。
Head Quality assurance -To review the investigation inmicrobiology and manufacturing area.
QA经理：审核微生物和生产领域的调查。
Procedure:
程序
Definition:
定义
Laboratory error: An error that occurs in a Laboratoryassociated with the performance of a test procedure, calculation error anddilution error or due to laboratory equipment malfunction or failure.
实验室错误：实验室发生的与测试程序的性能、计算错误和稀释错误或实验室设备故障或失效相关的错误。
Assignable cause: A scientifically justified explanationof the reason for an out-of specification or questionable test value uncoveredand documented during the investigation.
可归属的原因：在调查期间发现并记录的OOS或可疑测试值的原因的科学合理解释。
Alert Limit: Alert limits are intended to provide warningsof situations which merit investigation but not necessarily warrant correctiveaction. A series of excursions (3 alerts in a week in a particularmanufacturing area either by same monitoring technique or from any of themonitoring techniques) beyond Alert Limits should constitute an excursionbeyond an Action Limit.
警戒限：警戒限用于提供应予以调查但不一定需要纠正措施的警报。频繁超出警戒限（在特定生产区域一周 3 次超警戒）应视为超行动限。
Action Limit: A limits that, when exceeded, indicates aprocess may have drifted from its normal operating condition. Excursions beyondAction limits require a documented investigation and corrective actions toprocesses. Excursions beyond Action limits do not normally requireconsideration of action on products except when those excursions occur in GradeA areas
行动限：一个限度，当超出时，表示工艺可能偏离其正常状态。超出行动限需要对工艺进行书面的调查和纠正措施。超行动限通常不需要考虑对产品采取措施，除非发生在 A 级区域。
Negative controls: Negative controls that to be used toidentify a “false positive’’ test Result.
阴性对照：用于识别'假阳性'测试结果。
Whenever Microbiological data deviation results areobtained in below mentioned test, analyst involved in testing, willimmediately inform the results to Head Microbiology/ Designee andMicrobiological data deviation will be logged as per bellow:
一旦在下述测试中得到微生物数据偏离结果，参与测试的分析师应立即将结果通知微生物主任，微生物数据偏离应按照以下管记录：
Microbiological Data deviation Numbering procedure: QA Executive/Designeeto assign the Microbiological Data Deviation (MDD) Number as below
微生物数据偏离编号程序：QA人员分配微生物数据偏离（MDD）编号如下：
MDD/YY/XX
Where MDD Stands for Microbiological Data Deviation
MDD 代表微生物数据偏离
YY stands for year
YY表示年份
XX stands for Serial Number
XX表示序列号
A log book for all Microbiological Data Deviation (MDD)shall be maintained.
应维护所有微生物数据偏离（MDD）的台账。
Once the Microbiological Data Deviation results have beenidentified Head Microbiology/Designee should timely investigate (Laboratoryinvestigation). There should be no preconceived assumptions as to the cause offailure.
一旦确定微生物数据偏离结果，微生物主任应及时调查（实验室调查）。对失败的原因不应有先入为主的假设。
Mention the results obtained and details of the findingslike the date of testing and date of observation, etc.
描述获得的结果和结果的详细信息，如测试日期和观察日期等。
Head Microbiology/Designee will discuss the methodfollowed with the analyst; Review the analyst’s knowledge/ training andqualification for performing the test correctly. Investigate whether anyabnormal incidence was documented during the period when the test was carriedout e.g. certain obvious errors like spilling of the sample, error in transferof the sample, power failure of equipment (incubator, LAF etc).
微生物主任将讨论检验所采用的方法；审查检验人员正确执行测试的知识/培训和确认。调查在进行测试期间是否记录了任何异常情况，例如样品溢出、样品转移错误、设备电源故障（培养箱、LAF等）等明显错误。
Procedure for Environmental monitoring excursions:
环境监测偏离调查程序：
Action to be taken in case of Alert Limit Excursions
超警戒情况下需要执行的操作
If the microbial counts are found to be more than or equalto the alert limit, log Microbiological Data Deviation (MDD) .
当微生物计数大于或等于警戒限，应记录微生物数据偏离（MDD）。
Notify Head -Production and Head -QA through Notification.
通知生产负责人和QA经理。
Notify the environmental monitoring excursions in oneworking day from the observation of the excursion.
应在发现偏离情况的一个工作日内通知。
Carry out the investigation .
进行调查
Check for the working discipline and adherence to thestandard operating procedures.
检查工作方法和标准操作程序的符合情况。
Impart training to the operators / technicians, ifrequired.
如果需要，对操作人员/技术人员进行培训。
Observe the plate(s) of the next day for any evidence ofhigher count.
在第二天继续观察平皿，以确认计数是否更多。
Check the HVAC system for differential positive pressure,power failure, tripping of HVAC system, any deviation made by the operatorworking in the respective area and Entry log register for any new entrant.Record the details.
检查 HVAC 系统是否出现负压、电源故障、HVAC 系统的跳闸、在该区域内工作的操作员是否出现任何偏离以及是否有任何新的人员进入。记录详细信息。
If the counts above the alert limits are observed i.e., 3alerts in a week in a particular manufacturing area either by same monitoringtechnique or from any of the monitoring techniques, consider it as action limitand proceed for investigation as per the instructions given under Action LimitExcursions.
如频繁超警戒，在特定生产区域一周 3 次超出警戒限，应视为超行动限，并按照超行动限进行调查。
If out of alert limit results are observed in the criticaloperational area, then the sterility tubes/canisters shall be observed forevidence of any growth for the batch(s) manufactured on the day of the out ofalert limit observation. Sterility tubes/canisters of batches manufactured onthe previous days shall also be observed for any growth.
如果在关键操作区域发现超警戒结果，则应观察无菌检查的试管/容器，以确认超警戒当天生产的批次是否有菌检出。超警戒前几天生产的产品无菌检查试管/容器，也应观察是否有菌检出。
Action to be taken in case of Action Limit Excursions.
超行动限情况下需要采取的措施：
If the microbial counts are found to be more than or equalto the action limit, log Microbiological Data Deviation (MDD).
如微生物计数大于或等于行动限，应记录微生物数据偏离（MDD）。
Notify Head -Production and Head -QA through Notification.
应通知生产负责人和QA经理。
Notify the environmental monitoring excursions in oneworking day from the observation of the excursion.
应在发现偏离情况的一个工作日内通知。
Stop production and hold the release of batchesmanufactured during this period (from the date of monitoring and till the dateof availability of investigation results)
停止生产并暂停在此期间生产的批次放行（从监测之日起至调查结果出来）
Subject the area for disinfection and fumigation.
对该区域进行消毒和熏蒸。
Carry out microbiological monitoring of the area forconsecutive three days after completion of fumigation.
熏蒸完成后对该地区进行连续3天的微生物监测。
The area shall be released for processing only afteravailability of satisfactory environment monitoring data for 3 consecutive daysafter the fumigation.
只有在熏蒸后连续3天获得令人满意的环境监测数据后，才能使用该地区进行生产。
All the batches manufactured during the period shall besubjected to the additional sampling and microbial analysis.
在此期间生产的所有批次均需进行额外的取样和微生物分析。
Check for the working discipline and adherence tothe standard operating procedures.
检查工作情况和SOP遵守情况。
Impart training to the operators / technicians, ifrequired.
如有需要，对操作人员/技术人员进行培训。
Check the trends and observe the next day’s results.Review the testing conditions.
检查趋势并观察第二天的结果。审核测试条件。
Review of physical Environment condition of the room
审查该房间物理环境状况
Temperature
温度
Relative humidity
相对湿度
Differential Pressure.
压差
Non-Viable particle counts.
悬浮粒子
The observed microorganisms to be subjected foridentification and shall be reviewed for the following:
所检出的微生物应进行鉴定，并应审查以下：
Type of isolate-bacteria, yeast, molds (genus, species ifrequired),
细菌、酵母、霉菌的种类（属，必要时到种），
Is it a common environmental isolate?
是常见的环境分离菌吗？
Probable source of isolate (air, operators, extraneous),
可能的来源（空气、操作人员、外来的），
Was this isolate observed before?
以前有检出过这种菌吗？
Is it a laboratory contamination?
是实验室污染吗？
Type of isolate observed whether the isolate is sporeformer or non sporulating organism.
检出菌的类型是产芽孢微生物的还是不产芽孢微生物。
Whether the contaminant is observed in critical site (Areawhere the product, product contact surface or containers & closures areexposed) or non-critical site.
污染是在关键部位（产品接触面或容器暴露的区域）还是非关键部位检出。
Whether the contaminant is incidental (Excursion at onlyone location at a given time of exposure).
污染是否是偶然的（一定时间内只有一个偏离）。
Whether the contaminant is observed as airborne orresidual population over the surface of equipment/ floor/ wall.
是空气中？还是设备表面/地板/墙壁？
Whether the excursion is gradually increased fromexceeding alert level to action level.
是否逐渐从超警戒限增长为超行动限。
Whether the excursion is repeatedly observed above alertlimit in a particular location or facility.
该偏离是否为在在特定位置或设施中反复超警戒限。
The investigation team shall recommend corrective andpreventive actions.
调查小组应建议纠正和预防措施。
Any extra sampling if required, to evaluate the course ofaction, shall be discussed among the team and can be implemented.
小组应讨论并实施任何必要的额外取样以评估需要采取的措施。
Manufacturing and investigation team to ensure appropriatecorrective actions recommended by QA.
生产和调查小组，确保 QA 建议采取适当的纠正措施。
Depending upon the identified probable cause take suitablecorrective measures to eliminate the cause.
根据确定的可能原因采取适当的纠正措施来消除原因。
If reasons found for the exceeding count are related toactivities in the area, cleaning, disinfection, spraying of disinfectant orfogging and fumigation shall be carried out.
如果偏离的原因与该区域内的活动有关，应当进行清洁、消毒、喷洒消毒剂或雾化及熏蒸。
Review HVAC System – air velocity, air changes and filterintegrity record of LAF and HEPA filters.
查看 HVAC 系统– LAF 和 HEPA 过滤器的风速、换气次数和过滤器完整性记录。
Review of trend of the environmental monitoring data.
审查环境监测数据的趋势。
Perform additional cleaning, disinfections and fogging ifhigh counts are observed next day.
如果第二天观察到高的数据，进行额外的清洁、消毒和雾化。
Observe the sterility tubes for the evidence of anygrowth.
观察产品无菌检查试管以确认是否有菌检出。
The investigation reports shall be submitted to the HeadQA/Designee.
调查报告应提交给QA经理。
Quality Assurance Head shall review the investigationreport and, if required, he can call for the re-qualification of the area.
QA经理应审查调查报告，必要时，可以要求对该区域进行再确认。
These batches shall be released for dispatch only afterthe investigation is complete and it is confirmed that the batchesmanufacturing during this period are not affected.
这些批次只有在调查完成后才能放行，并应确认在此期间的批次生产不受影响。
All the investigations carried out shall be recorded inthe format. The copy of this investigation report shall be maintained withrespective batch manufacturing records.
所有进行的调查应进行记录。应复印调查报告并与相应的批记录一同保存。
If the routine personnel monitoring results are foundexceeding the alert/action limits, the concerned person shall be re-trained,re-sampled at the earliest as part of the corrective action.
如果发现日常人员监测结果超出警戒限/行动限，应尽早对相关人员进行再培训，重新取样，作为纠正措施的一部分。
If a trend of over alert/action limits (routine personnelmonitoring) occurs, the person shall be completely re-certified or re-assignedto new duties outside the aseptic area as part of the corrective action.
如果出现频繁超警戒/行动限（日常人员监测）的趋势，作为纠正措施的一部分，该人员应完全重新确认或重新分配到无菌区以外工作。
If any laboratory error is found in laboratoryinvestigation manager microbiology shall take appropriate corrective action& evaluate the impact on the out of limit results (OOL) obtained, ensuresthe CAPA & send the report to QA.
如果在实验室调查中发现了任何实验室错误，微生物主任应采取适当的纠正措施并评估所获得的超限结果（OOL）的影响，确保CAPA并将报告发至 QA。
If there is no laboratory error observed, for furtherinvestigation to be done in manufacturing by QA and Head production.
如果没有观察到实验室错误，QA 和生产经理应对生产过程进行进一步调查。
Note: If the excursions occur in the product contactsurfaces during batch manufacturing, consider the batch rejection.
注意：如果在批生产期间产品接触面发生偏离，请考虑拒绝该批次。
As part of the investigation, if exhaustive monitoring isplanned in the areas, perform the monitoring as per an approved protocol. Theprotocol as a minimum shall contain the details like type of monitoring, theareas to be monitored, acceptance criteria, and the reporting formats
作为调查的一部分，如果计划在该地区进行详尽的监测，则根据批准的方案进行。该方案至少应包含监测类型、需要监测的区域、接受标准和报告格式等详细信息。
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