藥品生產(chǎn)中的偏差調(diào)查

1、藥品生產(chǎn)中對偏差的調(diào)查藥品生產(chǎn)中對偏差的調(diào)查Investigation of Deviation偏差的調(diào)查偏差的調(diào)查 Investigation of Deviationn何謂偏差何謂偏差 Whats Deviationn定義定義 Definitionn實例實例 Examplesn分類分類 Classification偏差的調(diào)查偏差的調(diào)查 Investigation of Deviationn誰來處理偏差誰來處理偏差 Whos going to deal with deviations n質(zhì)量部門的職責(zé)質(zhì)量部門的職責(zé) Quality unit(s) responsibilityn生產(chǎn)作業(yè)的職責(zé)

2、生產(chǎn)作業(yè)的職責(zé) Production Activities responsibility 偏差的調(diào)查偏差的調(diào)查 Investigation of Deviationn如何對待偏差如何對待偏差 How should we do for deviationsn報告報告 Reportn調(diào)查調(diào)查 Investigaten后續(xù)檢查后續(xù)檢查Follow upn歸檔歸檔 Archive 何謂偏差何謂偏差 WhatWhats Deviations Deviationn對批準(zhǔn)的指令或規(guī)定的標(biāo)準(zhǔn)的對批準(zhǔn)的指令或規(guī)定的標(biāo)準(zhǔn)的偏離。偏離。 Departure from an approved Departure fr

3、om an approved instruction or established instruction or established standard. (ICH API GMP Guide)standard. (ICH API GMP Guide)偏差實例偏差實例 Deviation ExamplesDeviation Examplesn生產(chǎn)操作生產(chǎn)操作 Productionn包裝和貼簽包裝和貼簽 Packaging & Labelingn物料管理物料管理 Material Managementn設(shè)施和設(shè)備設(shè)施和設(shè)備 Facilities & Equipmentn實驗室控

4、制實驗室控制 Laboratory Controlsn質(zhì)量部門質(zhì)量部門 Quality Unitn驗證驗證Validationn員工培訓(xùn)員工培訓(xùn)Employee Training生產(chǎn)操作生產(chǎn)操作 Productionn關(guān)鍵工藝參數(shù)的實際值超出規(guī)定范圍關(guān)鍵工藝參數(shù)的實際值超出規(guī)定范圍 Actual results for critical process parameters exceed their specified rangen實際產(chǎn)率偏離預(yù)期范圍實際產(chǎn)率偏離預(yù)期范圍 Actual yields departure from their expected ranges包裝和貼簽包裝和貼簽

5、Packaging & Labelingn所用包裝材料無法追溯所用包裝材料無法追溯 The packaging materials used are not traceablen發(fā)出發(fā)出, ,使用和退回標(biāo)簽無法平衡使用和退回標(biāo)簽無法平衡 The quantities of labels issued, used, and returned are not reconciled物料管理物料管理 Material Managementn物料供應(yīng)商未經(jīng)質(zhì)量部門核準(zhǔn)物料供應(yīng)商未經(jīng)質(zhì)量部門核準(zhǔn) The material is not from the supplier approved by t

6、he quality unitn物料容器上沒有標(biāo)上指定的編號、批號物料容器上沒有標(biāo)上指定的編號、批號或接受號或接受號 The containers of material are not identified with the assigned distinctive code, batch, or receipt number設(shè)施和設(shè)備設(shè)施和設(shè)備 Facility & Equipmentn設(shè)施或設(shè)備的破損可能會影響產(chǎn)品質(zhì)量設(shè)施或設(shè)備的破損可能會影響產(chǎn)品質(zhì)量The damage on facility or equipment with potential impact on prod

7、uct qualityn關(guān)鍵儀器設(shè)備的校驗結(jié)果不符合規(guī)定的關(guān)鍵儀器設(shè)備的校驗結(jié)果不符合規(guī)定的標(biāo)準(zhǔn)標(biāo)準(zhǔn) Calibration results on critical instruments or equipment do not meet the approved standards 實驗室控制實驗室控制 Laboratory Controlsn實際測試結(jié)果不符合質(zhì)量規(guī)格實際測試結(jié)果不符合質(zhì)量規(guī)格 Actual testing results are Out Of Specificationsn所用的物料或儀器超出其有效期所用的物料或儀器超出其有效期 The materials or inst

8、rument used are out of their expiration dates質(zhì)量部門質(zhì)量部門 Quality Unitn沒有完整的產(chǎn)品質(zhì)量定期審核報告沒有完整的產(chǎn)品質(zhì)量定期審核報告 No complete regular quality reviews of APIn沒按規(guī)定進(jìn)行內(nèi)部審計（自查）沒按規(guī)定進(jìn)行內(nèi)部審計（自查）Internal audits (self-inspection) are not performed in compliance with the program驗證驗證 Validationn對驗證方案中關(guān)鍵參數(shù)范圍的偏離，對驗證方案中關(guān)鍵參數(shù)范圍的偏離，或

9、結(jié)果不符合規(guī)定的認(rèn)可標(biāo)準(zhǔn)或結(jié)果不符合規(guī)定的認(rèn)可標(biāo)準(zhǔn) Departure from the parameter ranges of critical steps or acceptance criteria in the approved validation protocol 員工培訓(xùn)員工培訓(xùn) Employee Trainingn員工不具備與其工作相稱的教員工不具備與其工作相稱的教育、培訓(xùn)和育、培訓(xùn)和/ /或經(jīng)歷等資格或經(jīng)歷等資格 Employees are notqualified by appropriate education, training and/or experience fo

10、r their job. 偏差分類偏差分類 Classificationn從從偏差的發(fā)生偏差的發(fā)生來分來分通常有三種通常有三種 Deviations may occure in 3 classesn偶發(fā)事故偶發(fā)事故 Incidentialn有意偏差有意偏差 Intentionaln無意偏差無意偏差 Unintentional偏差分類偏差分類 Classificationn根據(jù)偏差的潛在影響可分為重根據(jù)偏差的潛在影響可分為重大的和非重大的大的和非重大的 Deviations may be typed as critical or noncritical based on their potent

11、ial effects.偏差分類偏差分類 Classificationn重大偏差重大偏差 Critical deviation 必須進(jìn)行調(diào)查必須進(jìn)行調(diào)查 Require an investigationn非重大偏差非重大偏差 Noncritical Deviation 可以進(jìn)行調(diào)查可以進(jìn)行調(diào)查 May require an investigation誰來處理誰來處理 Who will handle itn質(zhì)量部門質(zhì)量部門 Quality Unit(s) 確保已經(jīng)對重大的偏差進(jìn)行了調(diào)查，確保已經(jīng)對重大的偏差進(jìn)行了調(diào)查，并已解決。并已解決。 Making sure that critical de

12、viations are investigated and solved誰來處理誰來處理 Who will handle itn生產(chǎn)作業(yè)生產(chǎn)作業(yè) Production Activities 確保所有的生產(chǎn)偏差都已報告、評價，對確保所有的生產(chǎn)偏差都已報告、評價，對重大的偏差已做了調(diào)查，并記錄結(jié)論。重大的偏差已做了調(diào)查，并記錄結(jié)論。Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and the conclusion

13、are recorded.如何對待偏差如何對待偏差 How should we don報告報告 Reportn調(diào)查調(diào)查 Investigaten后續(xù)檢查后續(xù)檢查Follow upn歸檔歸檔 Archive 報報 告告 Reportn發(fā)現(xiàn)偏差的員工及時記錄下列信息并報告發(fā)現(xiàn)偏差的員工及時記錄下列信息并報告主管主管 Record the following information & report to supervisor immediately:n時間、地點時間、地點 Time & placen會受影響的產(chǎn)品及其批號會受影響的產(chǎn)品及其批號 Product name &

14、lot number may be affectedn偏差描述偏差描述 Description of deviationn已知的原因已知的原因 Explain deviation as known報報 告告 Reportn主管按偏差的實際情況將主管按偏差的實際情況將其分類其分類 Supervisor classify the deviation偏偏 差差偶發(fā)事故偶發(fā)事故有意偏差有意偏差無意偏差無意偏差原因已知原因已知 影響大影響大原因已知原因已知 影響小影響小原因未知原因未知 影響小影響小原因未知原因未知 影響大影響大影響大影響大永久變更永久變更 影響小影響小永久變更永久變更影響大影響大非永久

15、變更非永久變更 影響小影響小非永久變更非永久變更 重大偏差，需調(diào)查重大偏差，需調(diào)查非重大，不需調(diào)查非重大，不需調(diào)查非重大，可調(diào)查非重大，可調(diào)查原因已知原因已知永久變更？變更控制和/或驗證原因已知原因已知 影響大影響大原因已知原因已知 影響小影響小原因未知原因未知 影響小影響小原因未知原因未知 影響大影響大報報 告告 Reportn記錄不需調(diào)查的偏差的原因、糾正記錄不需調(diào)查的偏差的原因、糾正或預(yù)防措施，以及相關(guān)物料的處理或預(yù)防措施，以及相關(guān)物料的處理意見意見 Record the assignable cause for deviations with no investigation requ

16、ired, corrective or prevention action(s), and proper disposition of the related material.報報 告告 Reportn主管在作決定前可咨詢有關(guān)人員主管在作決定前可咨詢有關(guān)人員Supervisor may consult with related person(s)n主管簽署記錄并按規(guī)定流轉(zhuǎn)審核主管簽署記錄并按規(guī)定流轉(zhuǎn)審核Supervisor signed the record and circulates for review or approval調(diào)調(diào) 查查 Investigationn若主管將偏差初定為重

17、要偏差，或無法確若主管將偏差初定為重要偏差，或無法確定偏差的原因或是否有不良影響，應(yīng)立即定偏差的原因或是否有不良影響，應(yīng)立即會同質(zhì)量部門進(jìn)行調(diào)查。會同質(zhì)量部門進(jìn)行調(diào)查。 If the initial examination by supervisor determines the deviation as critical, or it cannot determine an assignable cause or provide assurance of not having negative impacts, an investigation must be undertaken join

18、tly by quality unit and the supervisor immediately.調(diào)調(diào) 查查 Investigationn質(zhì)量部門發(fā)出偏差調(diào)查表，除了登錄偏差質(zhì)量部門發(fā)出偏差調(diào)查表，除了登錄偏差記錄表號或其主要情況外，根據(jù)偏差具體記錄表號或其主要情況外，根據(jù)偏差具體情況，記錄下列部分或全部調(diào)查內(nèi)容。情況，記錄下列部分或全部調(diào)查內(nèi)容。Quality unit issues a deviation investigation form. Besides the number of deviation record form or its main information, pa

19、rt or all of the following investigation information should be recorded according to the individual case of investigation.調(diào)調(diào) 查查 Investigationn操作者對程序的知曉和熟練程度操作者對程序的知曉和熟練程度 Operators familiarity and comfort lavel with proceduresn主記錄文件和主記錄文件和/ /或或SOPSOP的清晰和準(zhǔn)確度的清晰和準(zhǔn)確度Clarity and accuracy of Master Recor

20、d documentation and/or SOPn查閱有關(guān)的記錄查閱有關(guān)的記錄 Review appropriate executed records調(diào)調(diào) 查查 Investigationn供應(yīng)商的信息供應(yīng)商的信息 Supplier informationn外加的測試結(jié)果外加的測試結(jié)果 Testing results conducted additionallyn內(nèi)部審計（自檢）報告內(nèi)部審計（自檢）報告 Internal audit (self-inspection) reportsn資源分配情況及其有效性資源分配情況及其有效性 Resource allocation and availa

21、bility調(diào)調(diào) 查查 Investigationn滿足下列兩個條件后調(diào)查才能作結(jié)論滿足下列兩個條件后調(diào)查才能作結(jié)論 The investigation should not conclude until the following two conditions are satisfiedn偏差的原因及糾正和預(yù)防措施已確定偏差的原因及糾正和預(yù)防措施已確定 An assignable cause of the deviation and corrective and preventive action are determinedn對物料的影響已確定對物料的影響已確定 Impacts to re

22、lated material are determined后續(xù)檢查后續(xù)檢查 Follow-upn質(zhì)量部門以及與偏差有關(guān)的部門應(yīng)確保質(zhì)量部門以及與偏差有關(guān)的部門應(yīng)確保糾正和預(yù)防措施已經(jīng)執(zhí)行和或落實糾正和預(yù)防措施已經(jīng)執(zhí)行和或落實 Quality Unit and the department(s) related to the deviation should be responsible to ensure that Corrective and preventive action completed and/or arranged. 后續(xù)檢查后續(xù)檢查 Follow-upn作必要的變更驗證作必要

23、的變更驗證 Necessary Changes/Validationsn進(jìn)行必要的培訓(xùn)進(jìn)行必要的培訓(xùn) Necessary Training歸歸 檔檔 Archive n歸檔的文件應(yīng)包括下列內(nèi)容：歸檔的文件應(yīng)包括下列內(nèi)容： The following documents should be archived for the deviation:n有物料處理的完整的偏差報告有物料處理的完整的偏差報告 Completed Deviation Report with material disposition歸歸 檔檔 Archiven偏差調(diào)查表偏差調(diào)查表 Deviation investigation

24、 formn糾正及預(yù)防措施表糾正及預(yù)防措施表 Corrective and preventive Action formn該簽的名都已簽好該簽的名都已簽好 All required signatures have been obtained歸歸 檔檔 Archiven偏差的歸檔可用下列不同的方法偏差的歸檔可用下列不同的方法，只要有書面程序規(guī)定用哪種方法：只要有書面程序規(guī)定用哪種方法： The documents of deviation may be archived in the following ways, as long as it is defined in a written procedure.歸歸 檔檔 Archiven所有報告歸入批生產(chǎn)測試記錄，質(zhì)所有報告歸入批生產(chǎn)測試記錄，質(zhì)量部門只有偏差登記，若要看報告，量部門只有偏差登記，若要看