Personnel have science background & aretrained in routine laboratory practices but should also be made aware of GMPprinciples.
人員有科學(xué)背景并接受日常實(shí)驗(yàn)室操作的培訓(xùn)且應(yīng)使其了解GMP原則
Signed notebook records are kept ofproduction and testing activities. If batches fail, they are studied toincrease product and process knowledge.
應(yīng)保存生產(chǎn)和檢驗(yàn)活動(dòng)的簽字記錄。如果批次失敗，對(duì)其進(jìn)行研究以增加產(chǎn)品和工藝知識(shí)。
R&D activities are well documented inthe note books, as well as in periodic development reports.
研發(fā)活動(dòng)在記錄本和定期開發(fā)報(bào)告中都有很好的記錄。
There is a need to document source/pedigree/chain of custody of biological starting materials – cell ancestor andany animal materials used to create the initial cell line to the extentfeasible (Reference Section 6.0 and Section 3.3.2 of this technical report formore information).
有必要記錄生物起始物料（用于創(chuàng)建初始細(xì)胞系的細(xì)胞供體和任何動(dòng)物材料）的來源/譜系/保管鏈。
It is expected that a laboratory directorwith a science background is in charge of the Quality Unit (or equivalentfunction) and reviews all procedures and documents.
要求有科學(xué)背景的實(shí)驗(yàn)室負(fù)責(zé)人負(fù)責(zé)質(zhì)量部門(或同等職能)并審查所有程序和文件。
Use of batch records are highly recommendedbut could be generic.
強(qiáng)烈建議使用批記錄，但可以是通用的。
The Bulk Drug Substance is released byQA/QP after satisfactory review of the manufacturing and analytical records anddata (e.g., Completed batch record, analytical results, COA, environmental andwater monitoring data, deviations and changes), as well as compliance to theinvestigational new drug registration (e.g., IND, IMPD).
在對(duì)生產(chǎn)和檢驗(yàn)記錄和數(shù)據(jù)(如完整的批記錄、檢驗(yàn)結(jié)果、COA、環(huán)境和水監(jiān)測(cè)數(shù)據(jù)、偏差和變更)以及臨床試驗(yàn)新藥注冊(cè)(如IND、IMPD)的符合性進(jìn)行滿意審查后，散裝藥用物質(zhì)由QA/QP放行。
Manufacturing or testing deviations orunexpected events that do not impact product quality or patient safety shouldbe documented, but could be appended to the executed batch records. Formaldeviation and CAPA systems are recommended, albeit a simple and uncomplicatedsystem, with the level of investigation dictated by the severity of theincident.
應(yīng)記錄不影響產(chǎn)品質(zhì)量或患者安全的生產(chǎn)或檢驗(yàn)偏差或意外事件，但可添加在已執(zhí)行的批記錄中。建議使用正式的偏差和CAPA系統(tǒng)，即便是一個(gè)簡(jiǎn)單和不復(fù)雜的系統(tǒng)，調(diào)查級(jí)別由事件的嚴(yán)重程度決定。
Change management is important duringdevelopment of a product and the process to catalogues changes and facilitatesproduct /process understanding. A system should be in place at all GMPmanufacturing facilities.
變更管理在產(chǎn)品開發(fā)和對(duì)變更進(jìn)行分類并促進(jìn)產(chǎn)品/工藝?yán)斫獾倪^程中非常重要。在所有GMP生產(chǎn)設(shè)施都應(yīng)有一個(gè)系統(tǒng)。
Auditing/self-assessment is recommended,even though it is not mandated.
建議進(jìn)行審計(jì)/自檢，盡管這不是強(qiáng)制性的。
Testing or manufacturing conducted by athird party should be subject to a written agreement that might outline criticalquality expectations but a separate quality agreement may not be required.
由第三方進(jìn)行的檢驗(yàn)或生產(chǎn)應(yīng)遵守一份書面協(xié)議，說明關(guān)鍵的質(zhì)量期望，但單獨(dú)的質(zhì)量協(xié)議則可能不需要。
Responsibilities are governed by CGMP(e.g., ICH Q7 Eudralex - Volume 4 Good Manufacturing Practice Guidelines, andits Annex 13 by phase of development for some items (e.g., as methods are fullyvalidated or transferred, as master batch records are created). QA/QPresponsibilities must not be delegated to another functional area (unlessallowable by local law), but may be contracted to a qualified external serviceprovider.
職責(zé)由CGMP(例如，ICH Q7Eudralex - Volume 4 Good Manufacturing Practice Guidelines，及其附件13)管理，按某些項(xiàng)目的開發(fā)階段(例如，方法完全驗(yàn)證或轉(zhuǎn)移時(shí)，主批記錄創(chuàng)建時(shí))。QA) / QP的職責(zé)不能委托給其他職能部門(除非當(dāng)?shù)胤稍试S)，但可以委托給有資質(zhì)的外部服務(wù)提供商。
QA/QP takes a more active role in directinginvestigations and approving findings and CAPAs.
QA/ QP在管理調(diào)查、審批結(jié)果和CAPA方面發(fā)揮更積極的作用。
The reporting structure and hierarchy ofthe Quality Unit should ensure its ability to be independent from production.(From ICH Q7: There should be a quality unit(s) that is independent ofproduction and that fulfills both quality assurance (QA) and quality control(QC) responsibilities).
質(zhì)量部門的報(bào)告結(jié)構(gòu)和等級(jí)應(yīng)確保其可以獨(dú)立于生產(chǎn)。(來自ICH Q7:應(yīng)該有一個(gè)獨(dú)立于生產(chǎn)并同時(shí)履行質(zhì)量保證(QA)和質(zhì)量控制(QC)職責(zé)的質(zhì)量部門)。
Quality standards (e.g., policies, SOPs)must be reviewed and approved by QA. Even when these standards and procedureshave not been formally changed, they should be subject to periodic review inorder to ensure that they are still valid and up to date with actual practices.It is recommended that for each phase of clinical development, the relevantsummary development reports should be completed to review process
development activities and results. Thereports should include an evaluation of deviations and unexpected results thatare encountered during clinical production, scale up, tech transfer, characterizationstudies, etc.
質(zhì)量標(biāo)準(zhǔn)(如方針、標(biāo)準(zhǔn)操作規(guī)程)必須由質(zhì)量保證部門(QA)審核和批準(zhǔn)。即使這些標(biāo)準(zhǔn)和程序沒有正式變化，也應(yīng)定期審查，以確保它們?nèi)匀挥行?，并與實(shí)際做法保持一致。建議對(duì)于臨床開發(fā)的每個(gè)階段，都應(yīng)完成相關(guān)的總結(jié)開發(fā)報(bào)告，以審查工藝開發(fā)活動(dòng)和結(jié)果。報(bào)告應(yīng)包括在臨床生產(chǎn)、放大、技術(shù)轉(zhuǎn)移、特征研究等過程中遇到的偏差和意外結(jié)果的評(píng)估。
The Bulk Drug Substance is released by QA/QPafter review of the completed batch record, COA, environmental and watermonitoring data, deviations and changes, the investigational new drugregistration (e.g., IND, IMPD), and any other relevant information available inthe product specification file as specified in the procedures for batchrelease. QA/QP can delegate the release of manufactured intermediates to otherqualified personnel upon formalized agreements and acceptance.
散裝藥物物質(zhì)在完成對(duì)完整批記錄、COA，環(huán)境和水的監(jiān)測(cè)數(shù)據(jù)，偏差和變更，臨床試驗(yàn)新藥注冊(cè)(例如,IND,IMPD)，以及批放行程序中指定的產(chǎn)品標(biāo)準(zhǔn)文件中規(guī)定的其他任何相關(guān)信息的審核后，由QA / QP放行。在正式協(xié)議和任命后，QA/QP可以將所生產(chǎn)中間體的放行委托給其他有資質(zhì)的人員。
As clinical development proceeds, moredetailed batch records with acceptance criteria or target values should bedeveloped. Master batch records should be used prior to conducting processvalidation. Deviations should be recorded in the batch records as well asrequire formal investigations and CAPA. Deviation and investigations areincreasingly thorough as clinical development proceeds. By Phase 3 a formaldeviation tracking system and a CAPA system should be in place.
隨著臨床開發(fā)的進(jìn)行，應(yīng)該指定更為詳細(xì)的帶有接受標(biāo)準(zhǔn)或目標(biāo)值的批記錄。主批記錄應(yīng)在進(jìn)行工藝驗(yàn)證之前使用。偏差應(yīng)在批記錄中記錄，并要求正式調(diào)查和CAPA。隨著臨床開發(fā)的進(jìn)行，偏差和調(diào)查越來越徹底。在第三階段，正式的偏差跟蹤系統(tǒng)和CAPA系統(tǒng)應(yīng)到位。
Clinical materials should not bedistributed to external partners of the clinical supply chain until all opendeviations, test results, or other documentation are closed and approved byQA/QP.
在所有偏差、檢測(cè)結(jié)果或其他文件關(guān)閉并經(jīng)QA/QP批準(zhǔn)之前，不應(yīng)將臨床物料分發(fā)給臨床供應(yīng)鏈的外部合作伙伴。
Changes during the initial phases ofclinical development should be documented and justified based on the magnitudeof the change. Significant changes to the process should be conducted inaccordance with a written change management procedure and the IND should beupdated accordingly. As clinical development progresses a formal change controlprogram should be developed for Phase 3. Any potential impact of the change onon-going trials should be considered. Changes made during production operationsmust be reviewed by QA/QP during batch disposition.
在臨床開發(fā)開始階段的變更應(yīng)進(jìn)行記錄，并根據(jù)變更的大小進(jìn)行論證。工藝的重大變更應(yīng)按照書面變更管理程序進(jìn)行，IND也應(yīng)相應(yīng)更新。隨著臨床開發(fā)的進(jìn)展，應(yīng)該為第三階段制定一個(gè)正式的變更控制程序。變更對(duì)正在進(jìn)行的試驗(yàn)的任何潛在影響都應(yīng)予以考慮。在生產(chǎn)操作過程中所做的變更必須在批處理過程中由QA/QP進(jìn)行審核。
QA/QP audits should be conducted based upona risk assessment. Typically, fewer audits are conducted for early phasedevelopment operations and compounds.
應(yīng)基于風(fēng)險(xiǎn)評(píng)估進(jìn)行QA/QP 審計(jì)。通常，對(duì)開發(fā)早期階段的操作和合成進(jìn)行的審計(jì)較少。
