歐盟cgmp片劑清潔驗證方案(編輯修改稿)

　

【文章內容簡介】 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 當方案在執行的過程中，出現既定的內容或要求與實際執行情況或清潔 驗證 的目的不一致，需要對原批準方案進行改變，執行部門應按照《改變控制》文件編號SOPXXX的操作規程執行。 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規格）清潔驗證方案 編號： 頁碼： 9/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:9/50 驗證 內容 Content of cleaning validation 驗證 的準備工作 Preparation before cleaning validation 驗證 前，所有與清潔 驗證 有關的儀器、設備應進行 過校驗或確認。儀表、計量器具等應校驗合格，儀器、設備等應建立相應的操作、維護保養規程，對清潔 驗證 的樣品應建立相應的檢驗操作規程。本次清潔 驗證中制造部生產過程中所使用設備的確認情況及 QC 檢驗過程中所使用的儀器、設備、儀表、計量器具等確認或校驗情況見附件一。 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. 驗證 所需的試驗條件 /Testing condition needed for cleaning validation 、培養基。 Purified water, Culture Media 、試液、對照品等。 Reagents, solutions and reference standards 、器具等。 Instruments, utensils 。 Etc. SOP名稱及編號 /SOPs name and number regarding to cleaning 清潔 SOP名稱 SOPs name regarding to cleaning SOP編號 SOPs No. 題目： XXXX片（ 10mg規格）清潔驗證方案 編號： 頁碼： 10/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:10/50 、用品及設備 /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 、全自動洗衣機 。 Equipments for cleaning: UC3000Pultrasonic washing unit, automatic washer /Cleaning principle 各工序嚴格按照 自己工序使用的設備標準操作規程，在完成 XXXX 片 10mg規格 生產后，對本工序使用的設備及容器具進行清潔，清潔結束后通知 QC人員取樣檢測，要求 微生物及化學 檢測結果均符合規定的殘留限度要求。 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 設備名稱 Equipment Name 表面積 （ m2） Surface area 題目： XXXX片（ 10mg規格）清潔驗證方案 編號： 頁碼： 11/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:11/50 合計 Total 注：計算允許殘留限度時，總面積按照 2904dm2計算。 Notes: Permitted residual level is calculated based on 2904dm2 of total surface area. /Sampling locations 取樣點編號 Sampling No. 取樣位置（材質） 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規格）清潔驗證方案 編號： 頁碼： 12/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:12/50 取樣點編號 Sampling No. 取樣位置（材質） 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：取樣點示意圖見附件二 Note: Schematic diagram is shown as attachment 2 /Criteria of residual limit XXXX的最大殘留限度應設定為 25181。g/dm2。 Maximum permitted residual limit of XXXX is 25181。g/dm2 題目： XXXX片（ 10mg規格）清潔驗證方案 編號： 頁碼： 13/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:13/50 微生物殘留不得超過 20cfu/25cm2。 Microbial residual must not exceed 20cfu/25cm2 /Sampling procedure and method 取樣程序： 生產人員清潔結束后，通知 QC 人員取樣。取樣應在清潔完成 2 小時內取樣。取樣時，取樣人員首先對生產設備進行目檢，可接受標準為：目視無可見殘留。目檢合格方可取 樣。 取樣時先進行微生物取樣，再進行化測取樣。 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 若取樣點表面形狀規則，選擇面積為 100cm2的 PVC模板； If the surface of sampling location is regular, choose a 100cm2 of PVC template. 若取樣點表面形狀不 規則 ,使用不同規格 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表面上，用力使棉簽桿稍彎曲，以使棉簽一面與取樣 點表面完全接觸，平穩而緩慢地按圖一所示方向各均勻擦拭一遍，然后，翻轉棉簽，用另一面按圖二所示方向進行第二次擦拭。擦拭完畢，將棉簽頭置具塞試管中。對每個取樣點，用兩根棉簽重復取樣兩次，并將兩個棉簽頭置同一具塞試管中。擦拭過程應覆蓋整個 PVC模板內所有表面。取樣完畢，用 一次