【正文】 269,760 222,323 202,840 246,777備 注 ： “√”表示產(chǎn)品每批生產(chǎn)只與對應(yīng)的設(shè)備直接接觸一次；無“√ ”表示產(chǎn)品與對應(yīng)的設(shè)備無直接接觸；Remark: “√” means product has direct contact with equipment involved for one time。No more than % criterion: no more than % of the minimal effective dose of any product will appear in the maximum daily dose of the following product.千 分 之 一 原 則 No more than1/1000 criterion:硝苯地平允許在設(shè)備內(nèi)表面上的最大殘留量總和 R：allowable total maximum residue of Nifedipine left on inner surface of equipment R:最 大 允 許 殘 留 總 量 = 先 生 產(chǎn) 產(chǎn) 品 最 低 日 服 用 劑 量 (MTDD)/1000 x 后 續(xù) 生 產(chǎn) 產(chǎn) 品 批 量 /后 續(xù) 產(chǎn) 品 每 日 最大 劑 量MAR= minimum daily dose of previous product/1000 x batch size of subsequent product/Maximum daily dose of subsequent product（2）10ppm 原則：上一產(chǎn)品的主藥在下一產(chǎn)品中的含量不得超過 10ppm。如設(shè)備用乙醇清洗，則需過半小時后進(jìn)行目檢，確保設(shè)備內(nèi)表面無殘留。From the data in the table above, the three worst case products is for the continuously three batches cleaning validation.15 / 41六 清潔溶劑 Cleansing agents產(chǎn)品 A,E 和 F 所用設(shè)備的清潔溶劑如下：The cleansing agent for the product equipments used in product A, E and F are listed:設(shè)備名稱Equipment name文件編號Document Code設(shè)備清潔操作 SOPEquipment cleaning SOP所用清潔溶劑Cleansing agents usedGHJ50 高效混和機(jī)High Efficient MixerGHJ50 高效混和機(jī)清潔規(guī)程SOP for Cleaning High Efficient Mixer純化水 PW75%乙醇 75% EthanolPMA400 濕法制粒機(jī)PMA400 濕法制粒機(jī)清潔規(guī)程SOP for Cleaning PMA400 Wet Type Granulator純化水 PW75%乙醇 75% EthanolDFX400 流化床干燥器DFX400 流化床干燥器清潔規(guī)程SOP for Cleaning DFX 400 Fluid Bed Dryer純化水 PW75%乙醇 75% EthanolSL600 干式整粒機(jī) SL600 干式整粒機(jī)清潔規(guī)程 SOP for Cleaning SL600 Dry Type Straightening Granulator純化水 PW75%乙醇 75% EthanolHZD800 自動提升料斗混合機(jī)HZD800 自動提升料斗混合機(jī)清潔規(guī)程SOP for Cleaning HZD800 Automatic Lifting Hopper Mixer純化水 PW75%乙醇 75% EthanolS250/40EUB 壓片機(jī)S250/40EUB 壓片機(jī)清潔規(guī)程SOP for Cleaning S250/40EUB Tablet Press純化水 PW75%乙醇 75% EthanolGS HP 包衣機(jī) GS HP 包衣機(jī)清潔規(guī)程SOP for Cleaning GS HP Coating Machine純化水 PW75%乙醇 75% EthanolGFK2022 膠囊充填機(jī)GFK2022 膠囊充填機(jī)清潔規(guī)程Gelatine Capsule Filling and Closing Machine純化水 PW75%乙醇 75% EthanolUPS1030MTI 鋁塑包裝機(jī)UPS1030MTI 鋁塑包裝機(jī)清潔規(guī)程SOP for Cleaning UPS1030MTI Thermoforming Machine純化水 PW75%乙醇 75% EthanolFL350 風(fēng)冷式粉碎機(jī)Cooling air crusherFL350 風(fēng)冷式粉碎機(jī)SOP for Cleaning Cooling air crusher純化水 PW75%乙醇 75% Ethanol………. ………..以上設(shè)備均用純化水和乙醇清潔，無其他溶劑。 For product C, there is 2% dye in the it’s formulation, the dye is not the API, but still will affect the subsequent product, increase the risk of croscontamination. The visually check is used for it. We use the clean wet white tower scrub in the critical part of the equipment, see if the color is on the tower. For product G, the insoluble pigment is in the coating formulation, the visual check method is taken only for the coating machine. We use the clean white dry tower to scrub the scrub in the critical part of the equipment see if the color is on the tower.結(jié)論： 通過上表的分析，所選取的最壞情況產(chǎn)品為 A，E 和 F。在此我們采取目視方法，用白色濕抹布在設(shè)備關(guān)鍵部位擦拭，肉眼分辨其是否有顏色。Note: In practice, a value is remended that is within the lower third of the available dosing range with respect to the entire product range. 結(jié)論：由以上分組可知，產(chǎn)品 D 和產(chǎn)品 I 在溶解性，治療劑量和顏色氣味等方面均無風(fēng)險(xiǎn)，歸為無風(fēng)險(xiǎn)組。t meet requirements.微生物污染Microbial contamination低low培訓(xùn)衛(wèi)生管理相關(guān) SOPPersonnel should be trained for related SOP for hygiene management.是Yes是Yes9 / 412 最壞情況產(chǎn)品選擇 Worst case product Selection將產(chǎn)品按活性成分溶解性，治療劑量，處方（顏色，氣味，難溶成分）進(jìn)行分組，首先挑選出無風(fēng)險(xiǎn)的產(chǎn)品。 cleaning evaluation fails中medium對參加樣品檢測的分析人員進(jìn)行《清潔驗(yàn)證分析方法驗(yàn)證方案》和《微生物驗(yàn)證方案》培訓(xùn)考核。Performing validation of testing method of residue limit before performing this cleaning validation.是Yes是YesQA 人員取樣錯誤Wrong samples are taken by QA.不能得到準(zhǔn)確的檢測結(jié)果Inaccurate testing result高High在清潔驗(yàn)證方案中對取樣點(diǎn)進(jìn)行編號并用圖片的方式進(jìn)行標(biāo)識。s residue can39。 production supervisor and QA should check after cleaning是Yes是Yes取樣方法及取樣工具Sampling methods and tools取樣方法和工具使用不正確將會影響最終結(jié)果Misuse of sampling methods and tools will influence final result.高High對取樣人員進(jìn)行相關(guān)培訓(xùn)，明確取樣方法以及取樣時間。 cleaning operations don39。Ensure the normal working order and operation of HVAC, purified water system, pressed air, hot water for the cleaning validation. 清潔驗(yàn)證小組人員名單/Team Member List組 長 Team Leader部門 Dept. 崗位 Position 姓名 Name制造部 Production Dept. 業(yè)務(wù)經(jīng)理 Supervisor小組成員 Team Member部門 Dept. 崗位 Position 姓名 Name設(shè)備動力部 Engineering Dept. 業(yè)務(wù)經(jīng)理 Supervisor制造部 Production Dept. 工藝質(zhì)量員 Technician制造部 Production Dept. 生產(chǎn)協(xié)調(diào)員 Production Coordinator制造部 Production Dept. 工藝質(zhì)量員Production Coordinator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 leader5 / 41制造部 Production Dept. 技術(shù)員 TechnicianQC QC 主管 QC SupervisorQC理化 1 組組長Leader of physicochemical team 1QC 微生物組組長Leader of Microbial teamQC 微生物檢驗(yàn)員 AnalyzerQA QA 檢查員 QA inspectorQA QA 檢查員 QA inspectorQA QA 檢查員 QA inspectorQA 驗(yàn)證管理員Validation administrator6 / 41三 應(yīng)用范圍 Areas of application 本清潔驗(yàn)證主計(jì)劃應(yīng)用于固體車間所有產(chǎn)品。Archive the pleted cleaning validation documentation質(zhì)量保證部經(jīng)理：QA Manager批準(zhǔn)清潔驗(yàn)證方案、驗(yàn)證報(bào)告。According to requirements of GMP, the manufacturing equipments and rooms must be pletely cleaned to avoid contamination of different batches of same products or crosscontamination of different products after manufacturing of oral solid dosage. There are two types of cleaning method based on SOPs of Operation/ Cleaning and maintenance for individual equipments: implement the risk analysis assessment to choose the worst case products. Three consecutive cleaning validation will be conducted to validate the stability and reliability of cleaning method. All equipments and utensils used in manufacturing must be pletely cleaned once every batch of the worst case products are finis