GLP(良好实验室规范)课件

1、GLP(良好实验室规范)国家为了保证药品的质量安全制定的一系列规范，包括：GAP中药材生产质量管理规范 GMP药品生产质量管理规范 GLP药物非临床研究质量管理规范 GCP药物临床试验管理规范 （Good Clinical Practice） GSP药品经营质量管理规范GUP药品使用质量管理规范这些严格的规范被逐渐应用到其它相关领域，尤其是食品行业：GAP（Good Agricultural Practice ）:良好农业规范GMP（Good Manufacturing Practices） :良好操作规范GLP （Good Laboratory Practice ）:良好实验室规范GSP（G

2、ood Supplying Practice ）：良好经营（供应）规范1h第1页，共55页。GLP(良好实验室规范) GLP是英文Good Laboratory Practice 的缩写，中文直译为良好实验室规范。 GLP是就实验室实验研究从计划、实验、监督、记录到实验报告等一系列管理而制定的法规性文件，涉及到实验室工作的所有方面。它主要是针对医药、农药、食品、食品添加剂、化妆品、兽药等进行的安全性评价实验而制定的规范。 制定GLP的主要目的是严格控制化学品安全性评价试验的各个环节，即严格控制可能影响实验结果准确性的各种主客观因素，降低试验误差，确保实验结果的真实性。2h第2页，共55页。GL

3、P(良好实验室规范) GLP始于20世纪70年代。新西兰是第一个建立实验室登记法的国家。 1976年美国食品药品管理局（FDA）制定了仅限于药品的GLP规范草案。 1980年由美国联邦环保局（EPA）在联邦杀虫、杀菌、杀鼠剂法中发布了有关农药的GLP标准。加拿大、日本、韩国等国家先后发布了本国的GLP法规。 欧共体在1975年5月公布了关于药品药理毒理、临床及临床标准草案法规，在1986年提出GLP草案，1988年又发布GLP检查法令。欧共体GLP与经济合作与发展组织（OECD）的GLP原则一致。 1993年12月我国原国家药品监督管理局颁布了“药品非临床研究质量管理规定”(试行)。国家环境保

4、护总局等部委也先后制定了本行业的GLP标准。我国农药行业GLP工作始于2002年。 3h第3页，共55页。GLP(良好实验室规范)CONTENTS 内容1、整洁有序的实验室日常管理 GOOD HOUSEKEEPING PRACTICE2、安全规范 SAFETY PRACTICE3、符合专业要求的操作 GOOD OPERATIONAL PRACTICE4、纯净水 PURIFIED WATER5、标准物质 REFERENCE MATERIALS6、标准溶液 STANDARD SOLUTIONS7、留样 RETAINED SAMPLES8、实验室器皿的清洁 CLEANING OF LABORATOR

5、Y WARE9、化学通风橱 FUME CUPBOARDS10、层流通风柜（超净工作台） LAMINAR FLOW HOODS11、实验室能力验证 LABORATORY PROFICIENCY TEST4h第4页，共55页。现场的5S！GLP(良好实验室规范)1、GOOD HOUSEKEEIPNG PRACTICE整洁有序的实验室日常管理Work flow: A well organized laboratory should minimize the amount of backtracking and retracing of steps.工作流程：实验室的布置应合理有序，以有助于提高工作效

6、率。Labs shall be kept clean and tidy and free from unnecessary clutter and equipment.实验室应保持清洁，整齐，不放置不需要的物品和仪器。All gangways, aisles and exits will be free to allow easy access.通道，走廊和出口保持通畅。All equipment, glassware and other supporting instrumentation will be back in their proper place after use.所有仪器，玻

7、璃器皿和辅助器具使用后应放加原处。A label will be placed on each cupboard and draw to identify its contents.橱柜和抽屉应有标识。Most chemicals in the laboratory are potentially hazardous,they shall be properly labeled and separately stored.化学品应分类存放，并按性质作危害性标识。5h第5页，共55页。现场的EHS！GLP(良好实验室规范)2、SAFETY PRACTICE-1 安全规范Personnel wil

8、l wear durable clothing that covers the arms, legs, torso and feet. Open-tode shoes and sandals will not be worn. 实验室人员应穿着牢固的能遮盖手臂、腿、身体和脚的服装，不得穿着露趾鞋和拖鞋。A clean, fastened cotton laboratory coat will be worn. Laboratory coats will not be worn in refreshment areas or lunch rooms.应穿着紧身的棉质工作服，工作服不可穿进茶点休息

9、区域或食堂。Eye protection will be worn unless the analyst can demonstrate that adequate protection is provided by other means.实验室应配备保护眼睛的设施，否则应配戴护眼镜。Each laboratory has dedicated hand washing facilities-including soap and paper towels. Hands are washed on entering the laboratory before starting analysis,

10、 and when entering and exiting the laboratory for lunch or going to the toilet.实验室应配备专用洗手设施-包括清洁剂和纸巾。进入实验室开始分析前，离开实验室进餐厅和由餐厅回实验室，或去洗手间均须洗手。6h第6页，共55页。现场的EHS！GLP(良好实验室规范)2、SAFETY PRACTICE-2 安全规范Appropriate gloves are worn when handling substances that may be absorbed through the skin or that are corr

11、osive, harmful or may irritate the analyst.处理易被皮肤吸收或腐蚀有害或刺激性的物质时应带适当的手套。Characters of chemicals, such as “Flammable”, “Corrosive” etc. shall be correctly identified and labeled.化学品的特性，如“易燃”，“腐蚀”等应正确标识。Cylinders shall be fixed and clearly labeled.钢瓶应清楚标识，并固定。Cuts and grazes to the skin are adequately

12、 covered by suitable dressings.伤口和皮肤擦破处应适当地包扎敷裹。Personnel will not work in a laboratory alone.不可单独在实验室工作。Eating, drinking and smoking are prohibited in the laboratory at all times.任何时候均不得在实验室吃、喝和抽烟。7h第7页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-1符合专业要求的操作-试剂的使用与配制-1Solvent bottles are always cov

13、ered as they will readily absorb moisture and contaminants from the air.溶剂易吸收空气中的水分和污染物，溶剂瓶必须随时盖紧。A pipette will not be used to pipette directly from the bottle unless it is an automatic pipette. The remaining solvent is not returned to the stock bottle. It must be treated as waste.不可用移液管直接从瓶中移取溶剂或溶

14、液，应倾倒入容器内移取，剩余溶剂不可倒回贮液瓶，应作废弃物处理。A spatula or spoon will not be placed directly into the bottle for solids. The required quantity is decanted into another container from which the material will be retrieved. The remaining material will not be returned to stock bottle. It should be treated as waste.不可

15、用刮勺或匙直接从瓶中取用固体试剂，应在另一容器中倾入所需量。剩余试剂不可倒回原容器，应作废弃物处理。8h第8页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-2符合专业要求的操作-试剂的使用与配制-2Laboratory personnel shall be made aware of their responsibilities in the use of suitable reagents, solvents, culture media, reference materials and laboratory ware in terms of t

16、he types of analysis they conduct.实验室人员应明确其有责任根据所进行的测试使用适合的试剂、溶剂、培养基、参照物和实验室器皿。Any possible contamination, including Leftovers that has been returned to the containers.任何可能导致污染的操作，包括将取出未用完的试剂、溶剂、培养基、参照物放回容器，受影响的物质均应视为失效。INTEGRITY OF REAGENTSAll reagent containers shall be labeled and tightly closed.

17、 They shall bear the original label.所有试剂容器均应标识和盖紧。容器上的标贴必须为原标贴。INTEGRITY OF REAGENTS9h第9页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-3符合专业要求的操作-试剂的使用与配制-3The person responsible for the preparation of the reagent shall be identifiable either from the label or from records.试剂的配制人应在标贴上标识或在记录中写明。Labor

18、atory shall establish written procedures for preparation of reagent solutions and culture media. Records of such preparation shall be maintained.实验室应建立试剂溶液和培养基配制方法的文件。应保存配制记录。Records for reagent solutions shall include measured weights and volume, burette readings, pH readings, calculation of standa

19、rdization factor and solution concentration.试剂溶液配制记录应包括重量，体积，滴定管读数，PH读数标定因子的计算和溶液浓度。10h第10页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-4符合专业要求的操作-试剂的使用与配制-4The preparation record for culture media shall include medium name, batch number, amount prepared, pH before and after autoclaving autoclave t

20、ime and pressure.培养基的配制记录应包括名称、批号、配制量、压热锅处理前后的PH值，处理时间和压力。Where laboratory prepares its own media, the chemicals used for such preparation shall be verified to be of the appropriate quality before use.如实验室自己制备培养基，使用前应确认所用化学品符合质量要求。“hazardous substance” shall be kept separately from other reagents an

21、d held in locked cabinets.危险物质应与其它试剂分别存放，并加锁。11h第11页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-5符合专业要求的操作-试剂的使用与配制-5Preparation And Storage Of Culture media培养基的制备和存储Culture media must be prepared and stored at the specified temperature and under the specified conditions according to the manufactu

22、rers instructions or method requirements. Each lot of prepared or purchased culture media must verified for its effectiveness.培养基必须按照制造商的说明或方法要求在规定的温度和条件下制备和存放。无论是购买的或制备的培养基，其有效性必须验证。Prepared Plates of Culture Media: Poured plates of agar Media are especially vulnerable to infection, dehydration and

23、 chemical degradation. Aseptic preparation and storage are essential to protect plates from microbial infection.培养基制备平板，例如琼脂倾注平板，特别易受微生物侵染，脱水，和化学降解，为使平板不受微生物侵染，必须进行无菌制备和存放。12h第12页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-6符合专业要求的操作-试剂的使用与配制-6GR (Guaranteed reagents) 保证试剂 （优级纯）（一级） 绿色AR (Analytic

24、al reagents) 分析纯 （二级） 红色CP (Chemical pure) 化学纯 （三级） 蓝色LR (Laboratory reagents) 实验试剂 （四级） 中黄色Correctly Select Reagents 正确选用试剂GR: 用于精密度和准确度较高的分析AR: 用于常规分析工作CP: 通常不用于分析工作，尤其不适合配制标准溶液LP: 不适合用于分析工作此外，有特定用途的试剂纯度有高纯试剂，如光谱纯、色谱纯等。AR can be used for preparing standard solutions but not for standardization.分析纯

25、试剂可用于配制标准溶液，但不可用于标定。13h第13页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-7符合专业要求的操作-称量过程-1Glass vessels used to weigh material will not be wiped with a dry cloth as this causes static electricity build up in the container. Do not put material to be weighed in the weighing dish more than 2/3 of its v

26、olume.用于称量样品或试剂的玻璃器皿不可用干织物擦试以免产生静电。样品不能超过称量皿体积的2/3。All samples and containers are at the same temperature as the weighing device. Therefore, all materials are allowed to equilibrate to room temperature prior to use.所有样品和容器应与称量装置置于同一温度，以使所有物料使用前在室温下平衡。All weighing devices are calibrated or verified p

27、rior to use. Verification shall be conducted at and 2 times of target value.称量仪器使用前应校验或验证，验证应在1/2及2 倍目标称量值处进行。14h第14页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-8符合专业要求的操作-称量过程-2Bare hand can never touch the weights, clean gloves should be worn.不可用手接触砝码，应佩戴干净手套。Oven should be equilibrated at speci

28、fied temperature prior to testing the loss of weight on drying. Sample after drying shall be cooled for a fixed and constant time interval.进行干燥失重测试前，应先将烘箱开启在规定温度下达到平衡。干燥后样品的冷却时间应恒定。Properly place objects being dried in the desiccator, no stacking is allowed.在干燥器中的物体不可叠放。15h第15页，共55页。GLP(良好实验室规范)3、GO

29、OD OPERATIONAL PRACTICE-9符合专业要求的操作-容量器具的使用-1The use of drying solvents (e.g. acetone), compressed air and paper towels will be avoided, where possible, as these may be other sources of damage or contamination.尽可能避免使用干燥溶剂（如丙酮），压缩空气和纸巾以免可能的损坏或污染。Glass stoppers purchased with the volumetric flasks will

30、 remain with that flask.容量瓶的玻璃塞须保持原配。Use of pipettes: the solutions are not mouth pipetted irrespective of their nature.任何溶液均不可用移液管通过嘴吸取。All pipettes are inspected carefully prior to use. It will be checked for cracks in the tip; if present it will be discarded. Pipettes are clean and dry prior to u

31、se.移液管在使用前应检查顶端是否有裂纹；移液管使用前必须清洁干燥。16h第16页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-10符合专业要求的操作-容量器具的使用-2The pipette is rinsed at least twice with the sample solution before use.移液管使用前应至少用样品溶液润洗两次。When removing solution from a flask, sufficient volume is drawn to slightly above the mark, the solu

32、tion is allowed to draw down to the mark by touching the tip of the pipette to the flask surface. Any excess fluid from the pipette is wiped in a downward motion then the aliquot is delivered.当由容量瓶移出溶液时，溶液体积应略高于刻度，然后用移液管尖端接触溶量瓶表面的方法将溶液调节至刻度。Note: most pipettes are designed not to be expelled (i.e. l

33、iquid should remain in the tip after use).多数移液管都无须将残留液赶了（即将残留液留在移液管尖端）。Volumetric glassware can not be kept in heating environment, or in refrigerator or cooling cabinet. Do not hold the quantitative part of the volumetric glassware with hand.所有容量器具不能存放在加热环境下或冰箱内。使用时不能用手捂住容量部分。 17h第17页，共55页。GLP(良好实验

34、室规范)3、GOOD OPERATIONAL PRACTICE-11符合专业要求的操作-容量器具的使用-3Graduated measuring cylinders are read by placing them on an even bench, and observing the meniscus at eye level. Volume is equivalent to the bottom of the meniscus.刻度量筒放置于平坦的桌面上读数，视线应与弯月面同一水平，由弯月面底部读取体积。Items such as beakers, Erlenmeyer flasks an

35、d other glassware with rudimentary volume markings will not be used for measuring volume.带有粗刻度的器皿，如烧杯、三角瓶等玻璃器皿不可用于量度体积。All volumetric glassware shall be verified before use; Pipettes shall be verified once every 3 month, and auto pipettes verified daily before use, record quarterly; Whether volumetr

36、ic flask is verified quarterly shall be based on uncertainty contribution. All verification is recorded.所有容量器具使用前必须经过验证。移液管每三个月验证一次，移液枪每次使用前验证，并每三个月记录一次。容量瓶的验证根据它对方法结果的不确定度贡献在方法的SOP中注明是否需要每三个月验证一次。所有验证均须记录。18h第18页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-12符合专业要求的操作-容量器具的使用-4All measurable glass

37、ware, such as pipette and volumetric flask, should be verified with certified thermometer, weights should also be certified and in calibration status.容量器皿（如移液管和容量瓶）的验证应使用处理校验状态的有证温度计及砝码.Volumetric measurement is an essential element in an analytical laboratory as many types of determination require

38、specific dilutions and quantitative delivery of solutions.容量分析是分析实验室的基本内容，因为许多测试均涉及定量稀释和溶液的定量转移。Regardless of type of volumetric glassware, where accuracy is required, especially for quantitative analysis, all of such volumetric equipment shall be calibrated.容量仪器应恰当地维护和检查，任何容量分析玻璃器皿,只要有精确度的要求，尤其是定量分

39、析，所有这些仪器均应进行校验。19h第19页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-13符合专业要求的操作-容量器具的使用-5Coca-cola requires that “class A” glassware shall be used for volumetric analysis. Does this mean no calibration is necessary for any glassware marked “A”?可口可乐系统规定使用”A“级容量器皿，这是否意味着凡是标识”A“的容量器皿都不必要校验？甚至使用了十余年也无需验

40、证其是否仍符合A级要求吗？Is your Class A glassware supplied with a serialized certificate of precision?你的”A“级容量器皿有不重复编号的效证书吗？Glass A glassware need only be used where such volumetric accuracy is critical to the performance of the method and, where it is required, the glassware must be calibrated as conforming t

41、o Class A tolerance.A级玻璃器皿仅在容量准确性对方法结果而言为必须时才使用，当需要用A级时，必须校验以确认符合A级的容许误差。20h第20页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-14符合专业要求的操作-容量器具的使用-6Glassware used for measuring samples, standards and reagents for analytical procedures must be Class A.用于测量进行测试的样品、标准和试剂的玻璃器皿必须是A级。All plastic volumetric

42、 containers are Class B.所有塑料容量分析容器均是B级。Syringes and automatic tip pipettors are not listed as Class A.注射器和自动移液管不列为A级。21h第21页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-15符合专业要求的操作-样品处理Sample preparation: All preparations will be done to mininize the potential risk of contamination or degrading the

43、 material to be analyzed.样品制备应将待测物质潜在的污染和降解或变质可能性降至最小。22h第22页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-16符合专业要求的操作-记录保存Recording Professionally.记录保存应符合规范。Log book is usually not original record. Adequate information and raw data, such as calculation, shall be maintained.数据表通常并非原始记录，记录应包含充分的信息及原始

44、数据，例如计算。Record shall be made at the time when the activity is carried out, never do it afterwards.确保记录的实时性。避免任何形式的”补记“。23h第23页，共55页。GLP(良好实验室规范)3、GOOD OPERATIONAL PRACTICE-17符合专业要求的操作-培训A number of extraneous conditions may influence the precision of a given measurement. They include temperature, me

45、thod of delivery, depth of color of the solution, type of meniscus, calibration to contain or deliver a definite volume, and so forth. Thus proper training of personnel and continuing observation of their operations shall be instituted as part of the quality assurance process to minimize or eliminat

46、e problems associated with these extrinsic factors which can affect precise liquid measurements.许多外部条件将影响测试的精确性，例如温度，样品或溶液的转移方法，溶液颜色深度，液柱弯月面的形状，确定体积的容量或转移量的校验等。因此，恰当的人员培训，操作的持续监视应成为实验室品质保证过程的一部分，以减少或消除这些影响液体精确测量的外部因素。24h第24页，共55页。GLP(良好实验室规范)4、PURIFIED WATER-1 纯净水Purified water is one of the most cr

47、itical but most often neglected reagents used in laboratory operations. Use of improperly purified water may account for the failure of analysis.水是最重要而常被忽视的试剂之一，使用不合格的水可能会导致分析的失败。Distillation of water will not always ensure quality. The materials and construction of the distiller, and the character

48、of raw water all influence the quality of the distillate. The storage container, too, can significantly influence the purity of the water.蒸馏并不总能确保水的质量，蒸馏装置的材质和构造，以及原水的品质均影响蒸馏水的质量。储存容器也将显著地影响蒸馏水的质量。25h第25页，共55页。GLP(良好实验室规范)4、PURIFIED WATER-2 纯净水Stills need periodic cleaning to remove scale.蒸馏装置需定期清洁和

49、除垢。For more precise analysis, it may be necessary to use water distilled from quartz or all-borosilicate glass distillation system.要求较严格的分析可能需使用石英硼硅玻璃蒸馏装置精馏的水。Purified water can be defined as water that has been distilled and/or deionized so that it meets relevant standard or specifications.纯净水为经蒸馏和

50、/或去离子的水，以达到或高于相关的标准或规格。26h第26页，共55页。GLP(良好实验室规范)4、PURIFIED WATER-3 纯净水分析实验室用水国家标准一、二、三级实验室用水的技术指标（GB6682-92)名称一级二级三级PH值范围（25）-5.0-7.5电导率（25），S/cm. 0.115可氧化物质（以O2计），mg/L -0.080.4吸光度（254nm,1cm光程） 0.0010.01-蒸发残渣（105 2），mg/L -1.02.0可溶性硅（以SiO2计），mg/L 0.010.02-一级水用于有严格要求的分析实验，如液相色谱分析用水等。二级水用于无机痕量分析，如原子吸收光

51、谱分析用水等。三级水用于一般的分析工作。27h第27页，共55页。GLP(良好实验室规范)4、PURIFIED WATER- 4 纯净水Grade 1 water should be produced by further treatment of grade 2 water, for example by reverse osmosis or ion exchange followed by filtration through a membrane filter of pore size 0.2m to remove particle matter or re-distillation f

52、rom a fused silica apparatus.一级水可用二级水经过石英设备蒸馏，或离子交换或反相渗透再经0.2m孔径的薄膜过滤器处理获得。Grade 2 water can be produced by multiple distillation. Re-distillation can also use sub-boiling silica distillation apparatus.二级水可用多次蒸馏或离子交换等制得，二次蒸馏水一般可达到二级标准。第二次蒸馏也可采用石英亚沸蒸馏器。Grade 3 water can be produced by single distilla

53、tion, by ion exchange, or by reverse osmosis. Unless otherwise specified, it should be used for ordinary analytical work.三级水可用一次蒸馏，离子交换，或反相渗透制得。通常，三级水可用于普通的分析工作。28h第28页，共55页。GLP(良好实验室规范)5、REFERENCE MATERIALS- 1 标准物质Definitions(定义)：Reference Material (RM): A material or substance, one or more propert

54、ies of which are sufficiently well established to be used for the calibration of apparatus, the assessment of a measurement method, or for assigning values to materials.参照物（RM）：一种材料或物质，其一项或多项物性值得到充分确定，用于校验仪器和评价测量方法或确定材料的性能值。Certified Reference Material (CRM):A reference material, one or more of whos

55、e property values are certified by a technically valid procedure accompanied by or traceable to a certificate or other documentation which is issued by a certifying body.有证参照物（CRM)：一种材料或物质，其一项或多项特性值通过采用技术上获得认可的方法并可溯源至认可机构颁发的证书或其它的文件而获得认证。29h第29页，共55页。GLP(良好实验室规范)5、REFERENCE MATERIALS- 2 标准物质Certifie

56、d Reference materials 有证基准物A certified reference material can be defined as a homogeneous material with specific properties such as identity, purity, and potency that has been measured and certified by a qualified and recognized organization.有证基准物是经有资质并获得承认的机构测定和鉴证的具有特定性质，例如属性、纯度、强度的均匀物质。注：中国国家标准将有证

57、标准物质为一级和二级These materials are quite expensive and may or may not be used in everyday operations. They are often used to “calibrate” and/or assay so-called “working or secondary reference materials.日常操作可使用经有证基准物标定的”二次标准“。30h第30页，共55页。GLP(良好实验室规范)5、REFERENCE MATERIALS- 3 标准物质Care must be taken for the

58、 certified reference materials to ensure that they are packaged, stored and handled properly to prevent deterioration. Certificate and records of receipt and use shall be maintained.有证基准物必须妥善包装、存放和处置，以防止变质，应保存收货和使用记录及证书，计算时应按证书标明的含量。The laboratory shall assign suitable staff as monitor(s) for certif

59、ied reference materials. Their duties shall include ordering or assisting in the ordering of new reference materials, checking calculations of assays, refilling empty working supply containers, keeping lists of laboratory-available certified reference materials up to date.指定合适人员监控有证基准物，其职责包括订购或协助订购的

60、基准物，检查计算，向专用的空容器中补充基准物溶液，和更新实验室有证基准物清单。31h第31页，共55页。GLP(良好实验室规范)5、REFERENCE MATERIALS- 4 标准物质It is preferable to keep sign-in and sign-out log books. Each analyst using a certified reference material shall register the name of the reference material, the date and time it is taken and returned, and h