【正文】 速取樣棉簽，將其紅色按閥彎折 45176。取樣完畢，用一次性清潔布蘸 75％ 的乙醇擦拭被取樣點表面。取樣完畢，用 一次性清潔布 沾 75%的乙醇擦拭被取樣點表面。對每個取樣點，用兩根棉簽重復(fù)取樣兩次，并將兩個棉簽頭置同一具塞試管中。 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(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。 取樣時先進(jìn)行微生物取樣，再進(jìn)行化測取樣。取樣時，取樣人員首先對生產(chǎn)設(shè)備進(jìn)行目檢，可接受標(biāo)準(zhǔn)為：目視無可見殘留。 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。 Maximum permitted residual limit of XXXX is 25181。 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(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(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(yīng)設(shè)定為 25181。 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，要求 微生物及化學(xué) 檢測結(jié)果均符合規(guī)定的殘留限度要求。 Cleaning media: drinking water, purified water, pressed air and 75% ethanol ：清潔布；一次性清潔布。 Instruments, utensils 。 Purified water, Culture Media 、試液、對照品等。本次清潔 驗證中制造部生產(chǎn)過程中所使用設(shè)備的確認(rèn)情況及 QC 檢驗過程中所使用的儀器、設(shè)備、儀表、計量器具等確認(rèn)或校驗情況見附件一。 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）清潔驗證方案 編號： 頁碼： 9/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:9/50 驗證 內(nèi)容 Content of cleaning validation 驗證 的準(zhǔn)備工作 Preparation before cleaning validation 驗證 前，所有與清潔 驗證 有關(guān)的儀器、設(shè)備應(yīng)進(jìn)行 過校驗或確認(rèn)。偏差的調(diào)查應(yīng)按照 SOP《偏差的處理》文件編號 XXX執(zhí)行。 When the testing results are abnormal, follow the SOP the handling of out of specifications (Doc. No.:XXX) to investigate. 當(dāng)出現(xiàn)操作不符合 SOP要求時，執(zhí)行部門應(yīng)通知 QA，執(zhí)行偏差調(diào)查。 Ensure the normal working order and operation of HVAC, purified water system, pressed air, hot water for the cleaning validation. 題目： XXXX片（ 10mg規(guī)格）清潔驗證方案 編號： 頁碼： 8/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:8/50 /Execution of protocol 填寫 要求 /Filling of Raw Data 所有清潔 驗證 取樣記錄、檢驗結(jié)果應(yīng)記錄在批準(zhǔn)過的方案的相應(yīng)記錄表 格內(nèi)； All sampling records and testing results related cleaning validation should be filled in the corresponding tables within approved validation protocol. 記錄、數(shù)據(jù)的填寫、計算應(yīng) 審 核并簽字； Entry and calculation of raw data should be reviewed and signed QA應(yīng)檢查清潔 驗證 數(shù)據(jù)記錄是否完整、 是否符合規(guī)定。 Archive the pleted cleaning validation documentation 質(zhì)量 保證 部經(jīng)理： QA Manager 批準(zhǔn)清潔 驗證 方案、 驗證 報告。 The predetermined cleaning methods will be validated that these methods can effectively remove residual and satisfy the limit for chemical residual and microbial residual. The equipments and utensils which are cleaned by this method can be reused again. 題目： XXXX片（ 10mg規(guī)格）清潔驗證方案 編號： 頁碼： 6/50 Cleaning Validation Protocol of XXXX Tablets(10mg) No.: Page:6/50 /Responsibility /Production Dept. 組織清潔 驗證 方案及報告的起草； Prepare the cleaning validation protocol/report 確定設(shè)備表面積、清潔方法、取樣部位； Determine the surface area of equipments, cleaning method and sampling locations 制定清潔操作規(guī)程； Establish cleaning procedure 按清潔操作規(guī)程清潔設(shè)備和容器具； Clean equipments and utensils according to cleaning procedure 確保清潔記錄填寫完整； Make sure the pleteness of cleaning records 將完成的清潔 驗證 文件提交給 QA審查； Submit the finalized cleaning documentation to QA review 保證 部 /QA Dept. QC 審核清潔 驗證 方案 /報告； Review the cleaning validation protocol/report 制定清潔 驗證 取樣方法和檢測方法； Establish sampling method and analytical method of cleaning validation 對清潔后設(shè)備、容器具進(jìn)行取樣和檢測，報告檢驗結(jié)果； Sample and test cleaned equipments and utensils, then report the testing results. 使用在校驗有效期內(nèi)的儀器設(shè)備進(jìn)行檢測。 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: Watercleaning method and nonwatercleaning method. The cleaning method for XXX belongs to the former. Three consecutive cleaning validation will be conducted synchronously during process validation of 10mg strength Tablets to validate the stability and reliability of cleaning method on the basis of finishing cleaning verification of trial batch. All equipments and utensils used in manufacturing must be pletely cleaned once every batch of 10mg XXXX Tablets is finished, then sample to test chemical residual and microbial residual, the requirement is the level of residual is less than the limit of residual. Because API is not sieved during dispensing phase and directly put into a bag within a transferring container, only spoon contacting with API will be tested for chemical and microbial items, while other parts are only tested for micr