【文章內(nèi)容簡(jiǎn)介】 When the operations don’t meet the requirements specified in SOPs, the associated dept. should notify QA to make deviation investigation. It is required to describe the deviation occurance clearly and make reords. The evaluation focusing on the potential influence from the deviations should be done and the corrective actions must be approved. The deviation investigation should follow the SOP the handling of deviation (Doc. No.:XXX). /Change Control 當(dāng)方案在執(zhí)行的過(guò)程中，出現(xiàn)既定的內(nèi)容或要求與實(shí)際執(zhí)行情況或清潔 驗(yàn)證 的目的不一致，需要對(duì)原批準(zhǔn)方案進(jìn)行改變，執(zhí)行部門(mén)應(yīng)按照《改變控制》文件編號(hào)SOPXXX的操作規(guī)程執(zhí)行。 During implementing the protocol, when there happens some variance between the procedures specified in the protocol and actual situation or the purpose of validation and the approved protocol is in need of change, follow the SOP change control(Doc. No.: SOPXXX). 題目： XXXX片（ 10mg規(guī)格）清潔驗(yàn)證方案 編號(hào)： 頁(yè)碼： 9/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:9/50 驗(yàn)證 內(nèi)容 Content of cleaning validation 驗(yàn)證 的準(zhǔn)備工作 Preparation before cleaning validation 驗(yàn)證 前，所有與清潔 驗(yàn)證 有關(guān)的儀器、設(shè)備應(yīng)進(jìn)行 過(guò)校驗(yàn)或確認(rèn)。儀表、計(jì)量器具等應(yīng)校驗(yàn)合格，儀器、設(shè)備等應(yīng)建立相應(yīng)的操作、維護(hù)保養(yǎng)規(guī)程，對(duì)清潔 驗(yàn)證 的樣品應(yīng)建立相應(yīng)的檢驗(yàn)操作規(guī)程。本次清潔 驗(yàn)證中制造部生產(chǎn)過(guò)程中所使用設(shè)備的確認(rèn)情況及 QC 檢驗(yàn)過(guò)程中所使用的儀器、設(shè)備、儀表、計(jì)量器具等確認(rèn)或校驗(yàn)情況見(jiàn)附件一。 Before implementing the cleaning validation protocol, all instruments and equipments related to cleaning validation should be calibrated or verified. Instruments and gauges should be calibrated and within the calibration due date, instruments and equipments should have been established corresponding operation and maintenance procedure, and sample for cleaning validation have been established testing procedure. Attachment 1 is list of verification for equipments used in the manufacturing and instruments, equipments and gauges used in QC Lab. 驗(yàn)證 所需的試驗(yàn)條件 /Testing condition needed for cleaning validation 、培養(yǎng)基。 Purified water, Culture Media 、試液、對(duì)照品等。 Reagents, solutions and reference standards 、器具等。 Instruments, utensils 。 Etc. SOP名稱(chēng)及編號(hào) /SOPs name and number regarding to cleaning 清潔 SOP名稱(chēng) SOPs name regarding to cleaning SOP編號(hào) SOPs No. 題目： XXXX片（ 10mg規(guī)格）清潔驗(yàn)證方案 編號(hào)： 頁(yè)碼： 10/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:10/50 、用品及設(shè)備 /Media, articles and equipments for cleaning ：飲用水、純化水、壓縮空氣、 75％乙醇。 Cleaning media: drinking water, purified water, pressed air and 75% ethanol ：清潔布；一次性清潔布。 Articles for cleaning: cleaning cloth, singleservice cleaning cloth ： UC3000P型超聲波清洗機(jī) 、全自動(dòng)洗衣機(jī) 。 Equipments for cleaning: UC3000Pultrasonic washing unit, automatic washer /Cleaning principle 各工序嚴(yán)格按照 自己工序使用的設(shè)備標(biāo)準(zhǔn)操作規(guī)程，在完成 XXXX 片 10mg規(guī)格 生產(chǎn)后，對(duì)本工序使用的設(shè)備及容器具進(jìn)行清潔，清潔結(jié)束后通知 QC人員取樣檢測(cè)，要求 微生物及化學(xué) 檢測(cè)結(jié)果均符合規(guī)定的殘留限度要求。 Production staff should strictly follow the operating SOP for individual process and clean equipments and utensils used in the manufacturing after 10mg strength XXXX Tablets are finished, then inform QC analyst to sample. The object of clean is to make sure chemical residual and microbial residual meet predetermined criteria. /Surface area of individual equipments 設(shè)備名稱(chēng) Equipment Name 表面積 （ m2） Surface area 題目： XXXX片（ 10mg規(guī)格）清潔驗(yàn)證方案 編號(hào)： 頁(yè)碼： 11/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:11/50 合計(jì) Total 注：計(jì)算允許殘留限度時(shí)，總面積按照 2904dm2計(jì)算。 Notes: Permitted residual level is calculated based on 2904dm2 of total surface area. /Sampling locations 取樣點(diǎn)編號(hào) Sampling No. 取樣位置（材質(zhì)） Sampling locations(construction materials) T001※ T002※ T003※ T004※ T005※ T006※ T007 T008 T009 T010 T011 T012 T013 T014 T015 T016 T017 T018 T019※ T020 T021 T022 T023 T024 題目： XXXX片（ 10mg規(guī)格）清潔驗(yàn)證方案 編號(hào)： 頁(yè)碼： 12/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:12/50 取樣點(diǎn)編號(hào) Sampling No. 取樣位置（材質(zhì)） Sampling locations(construction materials) T025 T026 T027 T028※ T029 T030 T031 T032 T033 T034 T035 T036 T037 T038 T039 T040 T041 T042 T043 T044 T045 T046 T047 T048 T049 注：取樣點(diǎn)示意圖見(jiàn)附件二 Note: Schematic diagram is shown as attachment 2 /Criteria of residual limit XXXX的最大殘留限度應(yīng)設(shè)定為 25181。g/dm2。 Maximum permitted residual limit of XXXX is 25181。g/dm2 題目： XXXX片（ 10mg規(guī)格）清潔驗(yàn)證方案 編號(hào)： 頁(yè)碼： 13/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:13/50 微生物殘留不得超過(guò) 20cfu/25cm2。 Microbial residual must not exceed 20cfu/25cm2 /Sampling procedure and method 取樣程序： 生產(chǎn)人員清潔結(jié)束后，通知 QC 人員取樣。取樣應(yīng)在清潔完成 2 小時(shí)內(nèi)取樣。取樣時(shí)，取樣人員首先對(duì)生產(chǎn)設(shè)備進(jìn)行目檢，可接受標(biāo)準(zhǔn)為：目視無(wú)可見(jiàn)殘留。目檢合格方可取 樣。 取樣時(shí)先進(jìn)行微生物取樣，再進(jìn)行化測(cè)取樣。 Sampling procedure: QC staff will be informed to sample after production staff finish cleaning. Sampling should be performed within 2 hours once cleaning is finished. When sampling, these equipments should be visual inspected the firstly, the acceptable criteria: No visual residual. Sampling will not be conducted if visual inspection doesn’t meet the requirement. Microbiological sample should be sampled fisrtly, and then chemistry sample can be sampled secondly. /Sampling method /Sampling for API residual ? 選擇適宜的 PVC取樣模板 /Choose a suitable PVC sampling template 若取樣點(diǎn)表面形狀規(guī)則，選擇面積為 100cm2的 PVC模板； If the surface of sampling location is regular, choose a 100cm2 of PVC template. 若取樣點(diǎn)表面形狀不 規(guī)則 ,使用不同規(guī)格 PVC模板 ,必須保證被 取樣面積為 100cm2。 If the surface of sampling location is irregular and PVC sampling template can be used with different shapes, then sampling area must be not less than 100cm2. ? 取一燒杯，倒入適量色譜甲醇，將取樣用棉簽用色譜甲醇浸濕，在杯壁上擠掉棉簽上多余的溶劑；將棉簽頭按在取樣點(diǎn)表面上，用力使棉簽桿稍彎曲，以使棉簽一面與取樣 點(diǎn)表面完全接觸，平穩(wěn)而緩慢地按圖一所示方向各均勻擦拭一遍，然后，翻轉(zhuǎn)棉簽，用另一面按圖二所示方向進(jìn)行第二次擦拭。擦拭完畢，將棉簽頭置具塞試管中。對(duì)每個(gè)取樣點(diǎn)，用兩根棉簽重復(fù)取樣兩次，并將兩個(gè)棉簽頭置同一具塞試管中。擦拭過(guò)程應(yīng)覆蓋整個(gè) PVC模板內(nèi)所有表面。取樣完畢，用 一次