1、LABORATORY CONTROL SYSTEM,實(shí)驗(yàn)室控制體系 December 2005,CGMP GENERAL REQUIREMENT FOR LABORATORY CONTROLS 針對實(shí)驗(yàn)室控制，CGMP總體要求,21 CFR 211.160 (b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to

2、assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity. 實(shí)驗(yàn)室控制應(yīng)該包括建立科學(xué)合理的規(guī)范，標(biāo)準(zhǔn)，取樣方案，確保所有部件，藥品容器，蓋子，在制材料，標(biāo)簽和藥品符合適當(dāng)?shù)奶匦裕|(zhì)量，純度標(biāo)準(zhǔn),CGMP GENERAL REQUIREMENT FOR LABORATORY CONTRO

3、LS實(shí)驗(yàn)室控制CGMP總要求,21 CFR 211.160 (b) (1) Laboratory controls shall include實(shí)驗(yàn)室控制應(yīng)該包括 Determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of components, drug product containers, closures, and labeling used in the manufacture, processing,

4、packing, or holding of drug products . 適當(dāng)?shù)臅嬉?guī)范對于每一批在裝運(yùn)的部件驗(yàn)收，藥品器，蓋子，和在藥品制造，加工，包裝，存放的標(biāo)簽應(yīng)該一致。,CGMP GENERAL REQUIREMENT FOR LABORATORY CONTROLS實(shí)驗(yàn)室控制CGMP總要求,21 CFR 211.160 (b) (2) Laboratory controls shall include實(shí)驗(yàn)室應(yīng)該包括 Determination of conformance to written specifications and a description of sampling

5、 and testing procedures for in-process materials. Such samples shall be representative and properly identified. 取樣程序的書面描述和在制材料的測試程序應(yīng)該一致。像這樣的樣件應(yīng)該具有代表性和可辨性,CGMP GENERAL REQUIREMENT FOR LABORATORY CONTROLS實(shí)驗(yàn)室控制CGMP總要求,21 CFR 211.160 (b) (3) Laboratory controls shall include實(shí)驗(yàn)室控制應(yīng)該包括 Determination of co

6、nformance to written descriptions of sampling procedures and appropriate specifications for drug products. Such samples shall be representative and properly identified. 取樣程序的書面描述和藥品合適的規(guī)格應(yīng)該一致。像這樣的樣件應(yīng)該具有代表性和可辨性。,LABORATORY CONTROLS (Q7A)實(shí)驗(yàn)室控制,11.1 General Controls總控制 There should be documented procedu

7、res describing sampling, testing, approval, or rejection of materials and recording and storage of laboratory data 應(yīng)有文檔程序能描述材料取樣，測試，批準(zhǔn)，報(bào)廢，以及實(shí)驗(yàn)室數(shù)據(jù)的記錄和存儲 All specifications, sampling plans, and test procedures should be scientifically sound and appropriate to ensure that raw materials, intermediates,

8、APIs, and labels and packaging materials conform to established standards of quality and/or purity. 所有的規(guī)格，取樣計(jì)劃，和測試程序都應(yīng)該科學(xué)合理地確保原材料，中間體， APIs, 標(biāo)簽和包裝材料滿足所建立的質(zhì)量和純度標(biāo)準(zhǔn),CGMP GENERAL REQUIREMENT FOR LABORATORY CONTROLS實(shí)驗(yàn)室控制CGMP總要求,Establishment of Sampling plans Specifications Standards Test procedures 建立：

9、取樣計(jì)劃 規(guī)范 標(biāo)準(zhǔn) 測試程序,Testing for Components In-process materials Drug products (DS & DP) Containers and closures Labeling 測試： 部件 在制材料 藥品 容器和蓋子 標(biāo)簽,CGMP REQUIREMENT FOR LABORATORY CONTROLS實(shí)驗(yàn)室控制CGMP要求,How Do We Establish a Laboratory Control System to Meet CGMP Regulation? 我們應(yīng)該怎樣建立實(shí)驗(yàn)室的控制系統(tǒng)以此來滿足CGMP規(guī)則,STANDR

10、D OPERATION PROCEDUR (SOP)實(shí)驗(yàn)室標(biāo)準(zhǔn)操作程序,Global SOPs全球SOPs -Instrument, Method validation, Reagents 儀器，方法驗(yàn)證，和試劑 -Laboratory notebook, Documentation, etc. 實(shí)驗(yàn)手冊，文檔等等 Local SOPs國內(nèi)SOPs -Testing procedure, Calibration, etc. 測試程序，校對等等,LABORATORY CONTROL SYSTEM 實(shí)驗(yàn)室控制系統(tǒng),General Requirement總要求 The Laboratory faci

11、lities should be adequate and have adequate equipment for the facilitation of its function 實(shí)驗(yàn)設(shè)施應(yīng)該齊全，并且有足夠的設(shè)備用于其功能的設(shè)施 The responsible heads of various functional groups should have the necessary education, training, and experience to perform their functions 各職能組的負(fù)責(zé)人應(yīng)該具備必要的教育，培訓(xùn)和經(jīng)驗(yàn)以完成他們的功能 The Procedu

12、res for the proper cleaning, maintenance and storage of lab glassware/utensils should be in place 清洗，維護(hù)，和實(shí)驗(yàn)室的器皿/燒瓶的存放的程序應(yīng)該到位,LABORATORY CONTROL SYSTEM 實(shí)驗(yàn)室控制系統(tǒng),General Requirement總要求 Laboratory reagents and other chemical supplies should be identified and given expiration dates (and/or marked with da

13、te of a bottle is opened) 實(shí)驗(yàn)室儀器其它化學(xué)物品應(yīng)該查對和給定截止日期（或標(biāo)明瓶子打開的日期） USP reference standard should be used if it is available. Otherwise, in-house primary standard should be established 如有可能，USP 參考標(biāo)準(zhǔn)應(yīng)該采用。否則，過程質(zhì)量原始標(biāo)準(zhǔn)應(yīng)該建立。 The instrument shall be properly calibrated and maintained 儀器應(yīng)該恰當(dāng)?shù)男途S護(hù),RECORD RETENTIO

14、N實(shí)驗(yàn)室檔案的保存,All records (batch, electronic chromatographic data for HPLC analysis of drug components and finished products) should be backed up and maintained for at least one year after the expiration date 所有檔案（批次，藥品成分高性能液體色普電子色析數(shù)據(jù)和產(chǎn)成品）在截止日期過后，應(yīng)該至少保存一年。 A system should be in place to manage raw data

15、and laboratory notebooks 一系統(tǒng)應(yīng)該有可能處理原始數(shù)據(jù)和實(shí)驗(yàn)筆記 Daily use logbook should be kept for every instrument in laboratory 實(shí)驗(yàn)室里的每一儀器應(yīng)該放著日常使用的日志。,LABORATORY INSTRUMENTS實(shí)驗(yàn)室儀器,21 CFR 211.160 (b) (4) The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with

16、an established written program containing specific directions, schedules, limits for accuracy and precision, and previsions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shal

17、l not be used 儀器，裝置，檢具，記錄裝置的校準(zhǔn)，應(yīng)該以合適的間隔與包含具體方向，進(jìn)程，精確程度和為補(bǔ)救措施而做的準(zhǔn)備的已有的書面計(jì)劃一致，假如沒有達(dá)到精確或準(zhǔn)確程度。不滿足已有規(guī)格的儀器，裝置，檢具，和記錄裝置不應(yīng)該使用。,LABORATORY INSTRUMENTS實(shí)驗(yàn)室儀器,General總概 The laboratory instruments should be properly maintained and documented, and calibrated according to the written procedure(s) 實(shí)驗(yàn)室的儀器應(yīng)該如實(shí)維護(hù)和歸檔，并

18、且按照書面程序進(jìn)行校對 Use Logbook for instrument shall use hard bound book and be properly recorded and maintained 儀器上使用的日志要求使用硬面薄，并且做好記錄和維護(hù)好,CALIBRATION OF INSTRUMENTS實(shí)驗(yàn)室儀器校驗(yàn),Written Program (or SOP) 書面計(jì)劃（或SOP） - Specific directions具體方向 - Suitable intervals (schedule)合適間隔（進(jìn)程） - Parameters to be calibrated校對參

19、數(shù) - Acceptance criteria (limits)驗(yàn)收標(biāo)準(zhǔn)（限度） - Previsions for remedial action補(bǔ)救措施的準(zhǔn)備 Calibration Summary or Report校準(zhǔn)總結(jié)和報(bào)告,VALIDATION 驗(yàn)證,Overall policy should include validation process, cleaning procedures, analytical methods, in-process control test procedures, computerized system, and persons responsi

20、ble for design, review, approval 總的政策應(yīng)該包括驗(yàn)證程序，清洗程序，分析方法，在制控制測試程序，電算化系統(tǒng)和設(shè)計(jì)，評審，批準(zhǔn)負(fù)責(zé)人 All test methods used in a laboratory should be validated and documented before in use 所有的在實(shí)驗(yàn)室里使用的測試方法應(yīng)該在使用之前就該被驗(yàn)證和歸檔 USP test methods should be verified as suitable for actual use in testing of the product USP測試方法應(yīng)該被

21、證實(shí)是有效的，實(shí)際在使用上適合于產(chǎn)品測試。,VALIDATION 驗(yàn)證,Computer systems for control of process, data collection, etc. should be validated and documented 電腦系統(tǒng)中的程序控制，數(shù)據(jù)收集等等，應(yīng)該有效和歸檔 All components, manufacturing materials, in-process materials, packaging material, and labeling should be inspected and tested according to

22、written procedure(s) prior to release 所有的部件，制造材料，在制材料，包裝材料和標(biāo)簽，在發(fā)布之前應(yīng)該按照書面程序檢驗(yàn)和測試,STABILITY 穩(wěn)定性試驗(yàn),Stability protocol and appropriate storage conditions for stability program should be established 針對穩(wěn)定性計(jì)劃，穩(wěn)定性原型和合適的貯存條件應(yīng)該建立 Temperature and humidity of stability chamber should be validated and calibrated at regular intervals. Continuing chart recorder should be used to monitor temperature and humidity 具有穩(wěn)定性的房間里的溫度和濕度應(yīng)該不間斷的驗(yàn)證和校對 Stability program should include meaningful and specific test methods (stability indicating