【正文】 oluble 500 mg 活性成分含量最高Content of active pharmaceutical ingredient, is the highest in this groupC 20 % 不溶于水insoluble 200 mg E 5 % 幾乎不溶于水practically insoluble 10 mg 治療劑量最低therap. dose H 30 % 幾乎不溶于水practically insoluble 150 mg 此組選擇產(chǎn)品 A 和 E Choose product A and E in this group藥理組 Pharmacology risk group B 25 % 溶于水soluble 50 mg E 5 % 幾乎不溶于水practically insoluble 10 mg 溶解性最差Solubility, therap. dose F 50 % 溶于水Soluble 75 mg 活性成分含量最高Content of active pharmaceutical ingredient 此組選擇產(chǎn)品 E 和 F12 / 41Choose product E and F in this group處方風險組 Formulation risk group C 處方中有 2%的染料2% dye in the formulation 溶解性染料Soluble dye . 染料 Dye G 包衣層中有 1%的顏料1% pigment in film coating不溶解顏料Insoluble pigment . 顏料 Pigment 對于 C 產(chǎn)品，其處方中有 2%的可溶性染料，雖然不是活性成分，但也會對后續(xù)產(chǎn)品產(chǎn)生交叉污染。Analyzers involved in testing samples should be trained and assessed for Validation Protocol of Analytical Method in Cleaning Validation and Microbial Validation Protocol.是Yes是Yes人員衛(wèi)生不符合要求Personnel hygiene doesn39。t meet test of residue limit.不能得到準確的檢測結(jié)果Inaccurate testing result 高High在本驗證實施前進行殘留物限度檢測方法驗證。t meet standard硝苯地平殘留超標Residue of Nifedipine is over specifications 高High培訓相關清潔 SOP 培訓；清潔后由生產(chǎn)主管和 QA 檢查確認Operators should be trained for related cleaning SOPs。Approve the cleaning validation protocol and report 設備動力部/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，確保清潔驗證的實施。每批產(chǎn)品生產(chǎn)結(jié)束后，對所有在生產(chǎn)中使用的生產(chǎn)設備及容器具進行清潔，清潔后取樣檢測化學殘留及微生物殘留，要求殘留量低于設定的殘留限度要求。1 / 41上海金冀商務咨詢有限公司, Shanghai Jinji Business Consulting Co., Ltd文件編號：固體車間清潔驗證方案Cleaning validation Master Plan for Solid Dosage Workshop立項部門： 質(zhì)量保證部Initiation Department: Quality Assurance Department工藝驗證小組負責人： Leader of validation teem:方案制訂日期： 年 月 日 Date: Year Month Day2 / 41目 錄List of ContentOVERVIEW OF VALIDATIONVALIDATION ORGANIZAGION AND MEMBERSAREAS OF APPLICATIONRISK EVALUATION五 驗證方案表格VALIDATION MATRIX六 清潔溶劑CLEANSING AGENTSACCEPTANCE CRITERIACLEANING VALIATION AND SAMPLING九清潔驗證的實施IMPLEMENTATION OF CLEANING VALIDATION 十. 偏差、變更DEVIATIONS AND CHANGESREVALIDATION3 / 41一. 驗證概述 Overview of Validation1. 驗證目的根據(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。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 finished, then sample to test chemical residual and microbial residual, the requirement is the level of residual is less than the limit of residual.. Validation Organization and Team Members 制造部/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 質(zhì)量保證部/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對清潔后設備、容器具進行取樣和檢測，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)的儀器設備進行檢測。Ensure the normal working order and operation of HVAC, purified water system, pressed air, hot water for the cleaning validation. 清潔驗證小組人員名單/Team Member List組 長 Team Leader部門 Dept. 崗位 Position 姓名 Name制造部 Production Dept. 業(yè)務經(jīng)理 Supervisor小組成員 Team Member部門 Dept. 崗位 Position 姓名 Name設備動力部 Engineering Dept. 業(yè)務經(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. 技術員 Technician制造部 Production Dept. 工段長 Team leader制造部 Production Dept. 技術員 Technician制造部 Production Dept. 工段長 Team leader制造部 Production Dept. 技術員 Technician制造部 Production Dept. 工段長 Team leader5 / 41制造部 Production Dept. 技術員 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 微生物檢驗員 AnalyzerQA QA 檢查員 QA inspectorQA QA 檢查員 QA inspectorQA QA 檢查員 QA inspectorQA 驗證管理員Validation administrator6 / 41三 應用范圍 Areas of application 本清潔驗證主計劃應用于固體車間所有產(chǎn)品。 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對取樣人員進行相關培訓，明確取樣方法以及取樣時間。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.不能得到準確的檢測結(jié)果Inaccurate testing result高High在清潔驗證方案中對取樣點進行編號并用圖片的方式進行標識。t meet requirements.微生物污染Microbial contamination低low培訓衛(wèi)生管理相關 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）進行分組，首