欧盟cgmp片剂清洁验证方案

欧盟cgmp片剂清洁验证方案内容摘要：

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 当方案在执行的过程中，出现既定的内容或要求与实际执行情况或清洁 验证 的目的不一致，需要对原批准方案进行改变，执行部门应按照《改变控制》文件编号SOPXXX的操作规程执行。 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). 题目： XXXX片（ 10mg规格）清洁验证方案 编号： 页码： 9/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:9/50 验证 内容 Content of cleaning validation 验证 的准备工作 Preparation before cleaning validation 验证 前，所有与清洁 验证 有关的仪器、设备应进行 过校验或确认。 仪表、计量器具等应校验合格，仪器、设备等应建立相应的操作、维护保养规程，对清洁 验证 的样品应建立相应的检验操作规程。 本次清洁 验证中制造部生产过程中所使用设备的确认情况及 QC 检验过程中所使用的仪器、设备、仪表、计量器具等确认或校验情况见附件一。 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. 验证 所需的试验条件 /Testing condition needed for cleaning validation 、培养基。 Purified water, Culture Media 、试液、对照品等。 Reagents, solutions and reference standards 、器具等。 Instruments, utensils。 Etc. SOP名称及编号 /SOPs name and number regarding to cleaning 清洁 SOP名称 SOPs name regarding to cleaning SOP编号 SOPs No. 题目： XXXX片（ 10mg规格）清洁验证方案 编号： 页码： 10/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:10/50 、用品及设备 /Media, articles and equipments for cleaning ：饮用水、纯化水、压缩空气、 75％乙醇。 Cleaning media: drinking water, purified water, pressed air and 75% ethanol ：清洁布；一次性清洁布。 Articles for cleaning: cleaning cloth, singleservice cleaning cloth ： UC3000P型超声波清洗机 、全自动洗衣机。 Equipments for cleaning: UC3000Pultrasonic washing unit, automatic washer /Cleaning principle 各工序严格按照 自己工序使用的设备标准操作规程，在完成 XXXX 片 10mg规格 生产后，对本工序使用的设备及容器具进行清洁，清洁结束后通知 QC人员取样检测，要求 微生物及化学 检测结果均符合规定的残留限度要求。 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 设备名称 Equipment Name 表面积 （ m2） Surface area 题目： XXXX片（ 10mg规格）清洁验证方案 编号： 页码： 11/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:11/50 合计 Total 注：计算允许残留限度时，总面积按照 2904dm2计算。 Notes: Permitted residual level is calculated based on 2904dm2 of total surface area. /Sampling locations 取样点编号 Sampling No. 取样位置（材质） 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 题目： XXXX片（ 10mg规格）清洁验证方案 编号： 页码： 12/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:12/50 取样点编号 Sampling No. 取样位置（材质） 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：取样点示意图见附件二 Note: Schematic diagram is shown as attachment 2 /Criteria of residual limit XXXX的最大残留限度应设定为 25181。 g/dm2。 Maximum permitted residual limit of XXXX is 25181。 g/dm2 题目： XXXX片（ 10mg规格）清洁验证方案 编号： 页码： 13/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:13/50 微生物残留不得超过 20cfu/25cm2。 Microbial residual must not exceed 20cfu/25cm2 /Sampling procedure and method 取样程序： 生产人员清洁结束后，通知 QC 人员取样。 取样应在清洁完成 2 小时内取样。 取样时，取样人员首先对生产设备进行目检，可接受标准为：目视无可见残留。 目检合格方可取 样。 取样时先进行微生物取样，再进行化测取样。 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  选择适宜的 PVC取样模板 /Choose a suitable PVC sampling template 若取样点表面形状规则，选择面积为 100cm2的 PVC模板； If the surface of sampling location is regular, choose a 100cm2 of PVC template. 若取样点表面形状不 规则 ,使用不同规格 PVC模板 ,必须保证被 取样面积为 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.  取一烧杯，倒入适量色谱甲醇，将取样用棉签用色谱甲醇浸湿，在杯壁上挤掉棉签上多余的溶剂；将棉签头按在取样点表面上，用力使棉签杆稍弯曲，以使棉签一面与取样 点表面完全接触，平稳而缓慢地按图一所示方向各均匀擦拭一遍，然后，翻转棉签，用另一面按图二所示方向进行第二次擦拭。 擦拭完毕，将棉签头置具塞试管中。 对每个取样点，用两根棉签重复取样两次，并将两个棉签头置同一具塞试管中。 擦拭过程应覆盖整个 PVC模板内所有表面。 取样完毕，用 一次。