【正文】 Dept. 工段長 Team leader 制造部 Production Dept. 技術(shù)員 Technician 制造部 Production Dept. 工段長 Team leader 制造部 Production Dept. 技術(shù)員 Technician 制造部 Production Dept. 工段長 Team leader 制造部 Production Dept. 技術(shù)員 Technician 制造部 Production Dept. 工段長 Team leader 制造部 Production Dept. 技術(shù)員 Technician 制造部 Production Dept. 工段長 Team leader 制造部 Production Dept. 技術(shù)員 Technician QC QC主管 QC Supervisor QC 理化 1組組長 Leader of physicochemical team 1 QC 微生物組組長 Leader of Microbial team QC 微生物檢驗員 Analyzer QA QA檢查員 QA inspector QA QA檢查員 QA inspector QA QA檢查員 QA inspector QA 驗證管理員 Validation administrator 題目： XXXX片（ 10mg規(guī)格）清潔驗證方案 編號： 頁碼： 4/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:4/50 /General Introduction 根據(jù) GMP 的要求，在口服固體制劑生產(chǎn)結(jié)束后，要對生產(chǎn)設(shè)備及操作間進行徹底清潔，以避免造成不同批號或不同品種產(chǎn)品之間的污染和交叉污染。 為了 驗證 清潔方法 的穩(wěn)定性與可靠性 ， 在進行該產(chǎn)品10mg規(guī)格 工藝驗證的同時進行三次清潔驗證 。 因配料階段原料不進行篩分，稱重后放入塑料袋內(nèi)再放入中轉(zhuǎn)筒中儲存，所以配料階段 清潔后只對接觸原料的料鏟進行化學及微生物取樣，其它部位只進行微生物取樣。 Construction materials contacting with drug product is 304 or 316L stainless steel, cast iron or glass, etc. 驗證 目的 /Purpose of cleaning validation 驗證 制定的清潔程序可以使 XXX 的 殘留量 及微生物殘留量 符合制定的殘留限度的要求，清潔后的設(shè)備及容器具可以再次投入使用。 Use those instruments within calibration expired date QA 制定清潔 驗證 計劃及 驗證 編號； Establish cleaning validation plan and No. 負責組織審核清潔 驗證 的方案 /報告； Organize the review the cleaning validation protocol/report 組織清潔 驗證 相關(guān)部門進行清潔 驗證 方案的培訓并記錄； Organize the training and record for cleaning validation protocol 負責驗證實施過程的協(xié)調(diào)，保證驗證項目實施進度； Coordinate the activities of cleaning validation to ensure the performance. 題目： XXXX片（ 10mg規(guī)格）清潔驗證方案 編號： 頁碼： 7/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:7/50 驗證 實施中的監(jiān)控檢查； Supervise the validation activities. 保證經(jīng) 驗證 的參 數(shù)符合預(yù)期的標準； Make sure validated parameters meet predetermined criteria 負責組織 驗證 方案中改變控制、偏差處理的調(diào)查； Organize the investigation for the change control and deviation handling. 負責將完成的清潔 驗證 文件歸檔。 Approve the cleaning validation protocol and report /Engineering Dept. 保證 清潔 驗證 過程中，所用到的儀器儀表在校驗有效期內(nèi)； Ensure the instruments and meters involved in the cleaning validation have been calibrated and within calibration due date. 保證 驗證 過程中 空調(diào)、純化水、壓縮空氣、熱水等的供應(yīng)，確保清潔 驗證 的實施。 QA should check the pleteness of data records and make sure whether they are satisfied related requirements. 、 OOS/OOT的調(diào) /Deviation, OOS/OOT investigation 當檢測結(jié)果異常時，按照《檢驗結(jié)果超標情況的處理》文件編號 XXX的操作規(guī)程執(zhí)行。清楚地描述該偏差的情況、記錄文件、對于偏差的影響的評估并經(jīng)過批準、解決偏差所需采取的行動措施。 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(zhí)行的過程中，出現(xiàn)既定的內(nèi)容或要求與實際執(zhí)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(zhí)行部門應(yīng)按照《改變控制》文件編號SOPXXX的操作規(guī)程執(zhí)行。儀表、計量器具等應(yīng)校驗合格，儀器、設(shè)備等應(yīng)建立相應(yīng)的操作、維護保養(yǎng)規(guī)程，對清潔 驗證 的樣品應(yīng)建立相應(yīng)的檢驗操作規(guī)程。 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(yǎng)基。 Reagents, solutions and reference standards 、器具等。 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(guī)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(shè)備 /Media, articles and equipments for cleaning ：飲用水、純化水、壓縮空氣、 75％乙醇。 Articles for cleaning: cleaning cloth, singleservice cleaning cloth ： UC3000P型超聲波清洗機 、全自動洗衣機 。 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 Equipment Name 表面積 （ m2） Surface area 題目： XXXX片（ 10mg規(guī)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。g/dm2。g/dm2 題目： XXXX片（ 10mg規(guī)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。取樣應(yīng)在清潔完成 2 小時內(nèi)取樣。目檢合格方可取 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(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. 若取樣點表面形狀不 規(guī)則