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,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,10/21/2010,#,Testing and Inspection on components, in-process material and finished products,GMP Training,Module 7,1,General Requirements,基本要求,Do you have written procedures to monitor each stage of components, containers and closures? Show me an example.,How do you handle and store drug product containers and closures to prevent contamination?,Are drug containers or closures stored off the floor and can be easily inspected?,Do you have an identification code system to label and track the components?,Does each lot have a status label, such as approved, rejected or quarantined?,2,General Requirements,基本要求,(a) There shall be,written procedures,describing in sufficient detail the,receipt, identification, storage, handling, sampling, testing, and approval or rejection,of components and drug product,containers and closures,; such written procedures shall be followed.,(b) Components and drug product containers and closures shall at all times be handled and stored in a manner to,prevent contamination,.,(c) Bagged or boxed components of drug product containers, or closures shall be stored,off the floor,and suitably spaced to permit cleaning and inspection.,(d) Each container or grouping of containers for components or drug product containers, or closures shall be,identified with a distinctive code,for each lot in each shipment received. This code shall be used in recording the disposition of each lot. Each lot shall be appropriately identified as to its,status,(i.e., quarantined, approved, or rejected).,3,总要求,有文字详细说明成份、药品容器、密封件的签收、鉴定、贮存、装运取样、检验和批准或拒收程序，并遵循。,成份、药品容器和密封件应专人管理和在防止污染的环境下贮存。,药品容器的包装袋或包装箱或密封件应离地面放置保持适当间隔，全球清洁和检查。,用明显的已接收的每装货量中的批号代码对成分、药品容器或密封件加以鉴别。此代码用于记录每批货的放置地方。对每批货的情况，如隔离、批准或拒收等作检查。,4,Receipt and storage of untested components, drug product containers, and closures,接受未经测试原料,Do you perform visual check on received products?,Before a component is approved, where do you store them? How do you prevent them being used before being tested and approved?,5,Receipt and storage of untested components, drug product containers, and closures,原料接收,(a) Upon receipt and before acceptance, each container or grouping of containers of components, drug product containers, and closures shall be,examined visually for appropriate labeling,as to contents, container damage or broken seals, and contamination.,(b) Components, drug product containers, and closures shall be,stored under quarantine,until they have been tested or examined, whichever is appropriate, and released. Storage within the area shall conform to the requirements of 211.80 (general requirements).,6,未检验的成份、药品容器和密封件的接收与贮存,接收时和验收前，对每个或编组的成份容器、药品容器和密封件进行目检，给内容物、容器损坏或拆封和污染等情况作适当的标志。,成份、药品容器各密封件应隔离贮存，直至经检验为止。合格，可发放。在符合,21180,要求的地区中贮存。,7,Testing and approval or rejection of components, drug product containers, and closures,测试,Which department will sample, test and approve the component for use?,What statistical method are you following in determining sample size for testing? What is the acceptance criteria?,Do you keep reserve sample for active ingredients? How long and how many do you keep them?,8,Testing and approval or rejection of components, drug product containers, and closures,测试,(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by,the quality control unit,.,(b) Representative samples of each shipment of each lot shall be collected for testing or examination. The number of containers to be sampled, and the amount of material to be taken from each container, shall be based upon appropriate criteria such,as statistical criteria,for component variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required by 211.170.,9,成份、药品容器和封口物品的试验、批准或拒收,每批成份、药品容器和封口物品，在未经质量部门取样、检查合格前，不准使用。检验合格后发放使用。,收集每批的每一装货量的代表性样品，供检验用。容器数目和每一容器里物质的取样量是有适当的标准的，例如，成份的变异性统计学标准、可信限、要求的精密度、供应商过去的质量历史、,21170,要求分析和留样所需的数量等。,10,(c) Samples shall be collected in accordance with the following procedures:,(1) The containers of components selected shall be cleaned when necessary in a manner to,prevent introduction of contaminants,into the component.,(2) The containers shall be opened, sampled, and resealed in a manner designed to,prevent contamination,of their contents and contamination of other components, drug product containers, or closures.,(3) Sterile equipment and aseptic sampling techniques shall be used when necessary.,(4) If it is necessary to sample a component from the top, middle, and bottom of its container, such sample subdivisions shall not be composited for testing.,(5),Sample containers shall be identified,so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample.,(6) Containers from which samples have been taken shall be marked to show that samples have been removed from them.,11,How do you clean the containers of components? How do you verify it is clean?,During the operation, how do you control contamination ?,Do you identify sample containers so that the following information can be determined: name of the material sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and the name of the person who collected the sample?,12,收集样品程序,用适当的方法，清洁选出成份容器；,打开容器，取样，重新封口，防止其内容物受污染和其他成分、药品容器或密封件的污染。,必要时，使用灭菌设备和无菌取样技术。,如果需要从容器顶部、中部和底部的成分中取样，样品须混合。,鉴定样品容器，目的是确定如下资料：被取样的材料名称、批号、被取样的容器，取样日期及样品收集人的名字等。,已取样的容器，应作标志，表示样品已取出。,13,Do you do identity test for each component for drug?,Do you test each component for conformity with all appropriate written specifications for purity, strength, and quality? If so, please show me the written specification for PVP-I and your test result in March, 2010.,Do you also test containers and closures for conformity with all appropriate written specifications? If so, please show me the written specification for PVP-I and your test result in June, 2010.,14,(d) Samples shall be examined and tested as follows:,(1),At least one test,shall be conducted to verify the identity of each component of a drug product. Specific identity tests, if they exist, shall be used.,(2,) Each component,shall be tested for conformity with all appropriate written specifications for purity, strength, and quality. In lieu of such testing by the manufacturer, a,report of analysis,may be accepted from the supplier of a component, provided that at least one specific identity test is conducted on such component by the manufacturer, and provided that the manufacturer establishes the reliability of the suppliers analyses through appropriate validation of the suppliers test results at appropriate intervals.,(3),Containers and closures,shall be tested for conformity with all appropriate written specifications. In lieu of such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer and provided that the manufacturer establishes the reliability of the suppliers test results through appropriate validation of the suppliers test results at appropriate intervals.,15,样品检验程序：,一个药品的每个成分，最少做一个特性试验。如有专一特性实验就应采用。,依照所有成文的规格标准检验每个成份的纯度、含量和质量。生产厂家代替上述试验。规定生产厂家最少要做个成份特别试验，可承认；这些成分的供应者扫提供的分析报告。规定隔一定时间，生产厂家定期验证供应午的试验结果，证明供应者的分析结果是正确的。,依照成文规程，检验容器和密封件。生产厂家代替上述试验，规定生产厂家对这些容器或封口物品，最少做一次目检。可承认供应者的检验证书。规定生产厂家定期验证供应者的试验结果，证明其试验结果是正确的。,16,Do you microscopically examine your components?,Do you have established specifications for drug component, product container and closure for contamination?,How do you check for contamination before they are used?,17,(4) When appropriate, components shall be microscopically examined.,(5) Each lot of a component, drug product container, or closure that is liable to contamination with filth, insect infestation, or other extraneous adulterant shall be,examined,against established specifications for such contamination.,(6) Each lot of a component, drug product container, or closure with potential for microbiological contamination that is objectionable in view of its intended use shall,be subjected to microbiological tests before use,.,(e) Any lot of components, drug product containers, or closures that,meets the appropriate written specifications,of identity, strength, quality, and purity and related tests under paragraph (d) of this section may be approved and released for use. Any lot of such material that does not meet such specifications shall be rejected.,18,必要时，用显微镜检测成分。,每批易受污物、昆虫或其他外来杂物污染的某一成份、药品容器或密封件,应检测污染,.,每批易受污物、昆虫或其他外来杂物污染的某一成份、药品容器或密封件，鉴于其预期用途，在使用前，应做微生物试验。,任何批号的成份、药品容器或密封件，若符合已成文的均一性、效价或含量、质量、纯度等的规格标准和本部分（,d,）的有关试验，可批准使用。任何批号的上述材料，不符合这些规格，应拒收。,19,Use of approved components, drug product containers, and closures,使用顺序,When using components, drug containers and closures, do you follow FIFO (first in, first out) rule for approved samples?,Do you accept any deviations? If so, why? Show me a situation where some deviations are acceptable.,20,Use of approved components, drug product containers, and closures,Components, drug product containers, and closures approved for use shall be rotated so that the,oldest approved stock is used first,. Deviation from this requirement is permitted if such deviation is,temporary and appropriate,.,获准作用的成份、药品容器和密封件，先入库者先用。若产生的偏差是暂时的和适当，这种偏差是容许的。,21,Retesting of approved components, drug product containers, and closures,Components, drug product containers, and closures shall be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit in accordance with 211.84 as necessary, e.g., after storage for long periods or after exposure to air, heat or other conditions that might adversely affect the component, drug product container, or closure.,经质量控制部门批准或拒收的成份、药品容器密封件，若长期贮存或曝露在空气、热或其他可能对其产生不良影响的环境后，应依照,21184,，对均一性、效价或含量、质量、纯度等复检。,22,Rejected components, drug product containers, and closures,次品控制,How do you control rejected components, drug product containers, and closures from being used?,What is your identification system for rejected components, drug containers and closures?,Where do you store them and who has access to them?,23,Rejected components, drug product containers, and closures,Rejected components, drug product containers, and closures shall be,identified and controlled,under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable.,拒收的成份、药品容器和封口物品应经鉴定和在隔离系统下加以控制，防止在生产和加工使用。,24,Drug product containers and closures,药品密封容器和密封件,Are your drug product containers and closures reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug? How do you determine them?,How do you know your container closure systems can protect the drug product from foreseeable external factors?,25,Drug product containers and closures,(a) Drug product containers and closures shall not be reactive, additive, or absorptive so as,to alter the safety, identity, strength, quality, or purity,of the drug beyond the official or established requirements.,(b) Container closure systems shall provide,adequate protection against foreseeable external factors,in storage and use that can cause deterioration or contamination of the drug product.,(c) Drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. Such depyrogenation processes shall be validated.,(d) Standards or specifications, methods of testing, and, where indicated, methods of cleaning, sterilizing, and processing to remove pyrogenic properties shall be written and followed for drug product containers and closures.,26,药品密封容器和密封件,药品包装容器和密封件应不起反应、不吸着、不吸附、不致改变药品的安全性、均一性、含量或效价、质量和纯度而超出制定的或其它颁布的规定要求。,容器封口系统应对贮藏和使用过程中可预见的能引起药品变质或污染的外部因素提供足够的防护。,药品容器和密封件应清洁、灭菌和除热原，保证其适用于预期目的。,药品容器和密封件的标准或规格、检验方法（指清洁和消毒方法、除热原过程）应成文并遵循。,27,Sampling and testing of in-process materials and drug products.,To assure batch uniformity and integrity of drug products,written procedures,shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. Such control procedures shall include, but are not limited to, the following, where appropriate:,(1) Tablet or capsule weight variation;,(2) Disintegration time;,(3) Adequacy of mixing to assure uniformity and homogeneity;,(4) Dissolution time and rate;,(5) Clarity, completeness, or pH of solutions.,(6) Bioburden testing.,28,中间体和药品的取样与检验,制订和遵循说明每批的加工过程控制及对加工过程中材料的适当样品实行检验或检查的成文程序，保证药品的一致性和完整性。上述控制程序包括，但不限于如下内容：,片剂或胶囊的重量变化。,崩解时间。,充分混和，保证均匀。,溶解时间和溶解速率。,溶液的澄明度、溶解完全性及,PH,值。,29,Valid in-process specifications for such characteristics shall be consistent with drug product final specifications and,shall be derived from previous acceptable process average and process variability estimates,where possible and determined by the application of suitable statistical procedures where appropriate. Examination and testing of samples shall assure that the drug product and in-process material conform to specifications.,考虑上述特性而制定的有效中间加工规格与药品最终规格一致。此中间加工规格应在以前可靠的加工方法稳定性评估和经应用统计学程序断定认为合适的基础上制定的。样品测试，保证药品和中间体符合规格标准。,30,In-process materials shall be,tested for identity, strength, quality, and purity as appropriate, and approved or rejected by the quality control unit, during the production process, e.g., at commencement or completion of significant phases or after storage for long periods.,在生产加工期间，如在重要阶段的开始、由质量控制部门审定，决定取舍。,31,Rejected in-process materials shall be identified and controlled under a,quarantine system,designed to prevent their use in manufacturing or processing operations for which they are unsuitable.,不合格的中间体，在隔离系统下鉴别及控制，防止其在加工及操作中使用。,32,Drug product inspection,药品检查,Do you check the products and packages having the right label?,How many do you checked?,Show me the procedure and records of your label verification last week.,33,Drug product inspection,(a) Packaged and labeled products shall be examined during finishing operations to provide assurance that containers and packages in the lot have the,correct label,.,(b) A representative sample of units shall be collected at the completion of finishing operations and shall be,visually examined,for correct labeling.,(c) Results of these examinations shall be,recorded,in the,batch production or control records,.,34,药品检查,已包装和贴标签的产品，在结束工作时，应检查，保证本批容器和包装的标签正确无误。,操作结束时，每组收集一个代表性样品，同时检查标签。,检查结果记录在谬论批的生产或控制记录中。,35,Testing and release for distribution,Do you have final specifications for the drug product, including the identity and strength of each active ingredient, prior to release?,Show me an example each that finish product did or did not meet the final specifications.,Do you do bioburden test/microbial test on the finished product,？,What is your spec? Show me an example.,Do you have written procedures/sampling plan/sampling method for above testing?,36,Testing and release for distribution,测试批准发放,For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the,identity and strength of each active ingredient, prior to release,. Where sterility and/or pyrogen testing are conducted on specific batches of shortlived radiopharmaceuticals, such batches may be released prior to completion of sterility and/or pyrogen testing, provided such testing is completed as soon as possible.,发放前每批药品须经实验室测定，保证其符合药品的最终规格标准，包括特性和活性成份的含量。对有效期短的，需无菌和,/,或热原试验的放射药物特殊批号，可在上述试验完成前发放，规定尽快完成试验。,37,(b) There shall be appropriate laboratory testing, as necessary, of each batch of drug product required to be,free of objectionable microorganisms.,(c),Any sampling and testing plans,shall be described in written procedures that shall include the method of sampling and the number of units per batch to be tested; such written procedure shall be followed.,要求无有害微生物的药品，根据需要，每批药品应有适当的实验室检验。,任何取样和检验计划，应在成文程序中说明。此程序包括取样方法和每批检验的联合批号。,38,How do you know your current sampling plan and testing will assure the final products meet the release criteria and the statistical control criteria?,What is the statistical control criteria,/acceptance level,?,Are these testing method validated for,accuracy, sensitivity, specificity, and reproducibility,?,Do you reject the products that fail to meet spec? At what circumstance, are they allowed to be reprocessed?,What is your written procedure for reprocessing? Show me an example of reprocessing.,39,(d) Acceptance criteria for the sampling and testing conducted by the quality control unit shall be adequate to assure that batches of drug products,meet each appropriate specification and appropriate statistical quality control criteria,as a condition for their approval and release. The statistical quality control criteria shall include appropriate,acceptance levels,and/or appropriate,rejection levels,.,对质量控制部门的取样和检验的接收标准是满足保证那些药品符合各自的规格标准和统计学的质量控制标准。；这些标准是批准和发放药品的条件。此统计学质量控制标准包括适当的接收水平和,/,或适当的拒收水平。,40,(e) The accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented.,Such validation and documentation,may be accomplished in accordance with 211.194(a)(2).,(f) Drug products failing to meet established standards or specifications and any other relevant quality control criteria shall be,rejected,. Reprocessing,may be,performed. Prior to acceptance and use,reprocessed material must meet,appropriate standards, specifications, and any other relevant critieria.,证实和提供文件证明经严格使用的检验方法的准确性、灵敏性、特异性和重复性。此验证和证明，可按照,211194,（,a,）,(2),项完成。,不符合制订的标准、规格和其他有关质量控制标准的药品，应拒收，但可返工。被 返工的药品。在接收和应用前，须符合标准、规格和其他有关标准。,41,
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