5.44 Written procedures should be available for the operation and maintenance of computerized system. 5.44 应当有计算机化系统操作和维护的书面程序。
5.45 Where critical data are being entered manually, there should be an additional check on the accuracy of the entry. This can be done by a second operator or by the system itself. 5.45 手工输入关键性数据时，应当另外检查输入的准确性。这可由第二位操作人员或系统本身来进行。
5.46 Incidents related to computerized system that could affect the quality of intermediates or APIs or the reliability of records or test results should be recorded and investigated. 5.46 应当加以记录可能影响中间体或原料药质量、或者记录或测试结果可靠性的与计算机化系统有关的偶发事件，并作调查。
5.47 Changes to computerized system should be made according to a change procedure and should be formally authorized, documented, and tested. Records should be kept of all changes, including modifications and enhancements made to the hardware, software, and any other critical component of the system. These records should demonstrate that the system is maintained in a validated state. 5.47 对计算机化系统所作的变更应当按照变更程序进行，并应当经过正式批准、记录成文并作测试。所有变更记录都应当保存，包括对系统的硬件、软件和任何其它关键组件的修改和升级。这些记录应当证明该系统维持在验证过的状态。
5.48 If system breakdowns or failures would result in the permanent loss of records, a back-up system should be provided. A means of ensuring data protection should be established for all computerized system. 5.48 如果计算机的故障或失效会导致记录的永久丢失，则应当提供备份系统。所有计算机化的系统都应当有数据保护措施。
5.49 Data can be recorded by a second means in addition to the computer system. 5.49 除计算机系统之外，数据可以用第二种方式记录。
6. DOCUMENTATION AND RECORDS 6. 文件和记录
6.1 Documentation System and Specifications 6.1 文件系统和质量标准
6.10 All documents related to the manufacture of intermediates or APIs should be prepared, reviewed, approved, and distributed according to written procedures. Such documents can be in paper or electronic form. 6.10 与中间体或原料药生产有关的所有文件都应当按照书面程序进行拟定、审核、批准和分发。这些文件可以是纸张或电子形式。
6.11 The issuance, revision, superseding, and withdrawal of all documents should be controlled by maintaining revision histories. 6.11 所有文件的发放、修订、替换和收回应当通过保存修订历史来控制。
6.12 A procedure should be established for retaining all appropriate documents (e.g., development history reports, scale-up reports, technical transfer reports, process validation reports, training records, production records, control records, and distribution records). The retention periods for these documents should be specified. 6.12 应当制订一个保存所有适用文件（如开发历程报告、扩产报告、技术转移报告、工艺验证报告、培训记录、生产记录、控制记录和分发记录）的程序。应当规定这些文件的保存期。
6.13 All production, control, and distribution records should be retained for at least 1 year after the expiry date of the batch. For APIs with retest dates, records should be retained for at least 3 years after the batch is completely distributed. 6.13 所有生产、控制、销售记录都应保留至该批的有效期后至少一年。对于有复验期的原料药，记录应当保留至该批全部发出后三年。
6.14 When entries are made in records, these should be made indelibly in spaces provided for such entries, directly after performing the activities, and should identify the person making the entry. Corrections to entries should be dated and signed and leave the original entry still legible. 6.14 做记录时，应当在刚做操作活动后就在所提供的空白处以不易擦掉的方式填写，并标明填写者。修改记录时应当注明日期、签名并保持原来的记录仍可识读。
6.15 During the retention period, originals or copies of records should be readily available at the establishment where the activities described in such records occurred. Records that can be promptly retrieved from another location by electronic or other means are acceptable. 6.15 在保存期间，记录的原件或副本都应保留在记录中描述的活动发生的地方。能以电子或其它方式从另一地点即时恢复的记录也可以接受。
6.16 Specifications, instructions, procedures, and records can be retained either as originals or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records. Where reduction techniques such as microfilming or electronic records are used, suitable retrieval equipment and a means to produce a hard copy should be readily available. 6.16 质量标准、指令、规程和记录保存方式可以是原件，或者真实的副本如影印本、缩微胶卷、缩微平片，或其它原始记录的准确复制件。在使用压缩技术如缩微胶卷或电子记录时，应当有适当的制备纸张副本的恢复设备和方法。
6.17 Specifications should be established and documented for raw materials, intermediates where necessary, APIs, and labeling and packaging materials. In addition, specifications may be appropriate for certain other materials, such as process aids, gaskets, or other materials used during the production of intermediates or APIs that could critically affect quality. Acceptance criteria should be established and documented for in-process controls. 6.17 应当制订原料、中间体（必要时）、原料药和标签及包装材料的质量标准。此外，应当为工艺助剂、垫圈，或中间体或原料药生产中使用的能决定性地影响质量的物料制订质量标准。中间控制应当制定可接受的标准，并成文备查。
6.18 If electronic signatures are used on documents, they should be authenticated and secure. 6.18 如果文件采用电子签名，它们应当经过证实，并且确保其安全可靠。
6.2 Equipment cleaning and Use Record 6.2 设备的清洁和使用记录
6.20 Records of major equipment use, cleaning, sanitation, and/or sterilization and maintenance should show the date, time (if appropriate), product, and batch number of each batch processed in the equipment and the person who performed the cleaning and maintenance. 6.20 主要设备的使用、清洁、消毒和/或灭菌和保养记录应当记有日期、时间（如有必要的话）、产品、设备中加工的每批批号以及进行清洁和保养的人。
6.21 If equipment is dedicated to manufacturing one intermediate or API, individual equipment records are not necessary if batches of intermediate or API follow in traceable sequence. In case where dedicated equipment is employed, the records of cleaning, maintenance, and use can be part of the batch record or maintained separately. 6.21 如果设备专门用于一种中间体或原料药的生产，而且该中间体或原料药的批号有可追溯性的顺序，那就不需要有单独的设备记录。专门设备的清洁、保养及使用记录可以作为批记录的一部分或单独保存。
6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 6.3 原料、中间体、原料药的标签和包装材料的记录
6.30 Records should be maintained including:
● The name of the manufacturer, identity, and quantity of each shipment of each batch of raw materials, intermediates, or labeling and packaging materials for API’s; the name of the supplier; the supplier’s control number(s), if known, or other identification number; the number allocated on receipt; and the date of receipt
● The results of any test or examination preformed and the conclusions derived from this
● Records tracing the use of materials
● Documentation of the examination and review of API labeling and packaging materials for conformity with established specifications
● The final decision regarding rejected raw materials, intermediates, or API labeling and packaging materials 6.30 需保存的记录应当包括：
● 每次到货的每批原料、中间体、原料药标签和包装材料的生产商的名称，标识和数量；供应商的名称、供应商的管理编号，或其它识别号码；物料接收编号和接收日期；
● 所进行的任何测试或检查结果，以及由此得出的结论；
● 跟踪物料使用的记录；
● 检查和审核原料药的标签和包装材料与规定标准符合度的证明文件；
● 拒收原料、中间体或原料药的标签和包装材料的最终决定。
6.31 Master (approved) labels should be maintained for comparison to issued labels. 6.31 标准标签（已批准的）应当保留，用来与发放的标签作比较。
6.4 Master Production Instructions (Master Production and Control Records) 6.4 生产工艺规程（主生产和控制记录）
6.40 To ensure uniformity from batch to batch, master production instructions for each intermediate and API should be prepared, dated, and signed by one person and independently checked, dated, and signed by a person in the quality unit(s). 6.40 为确保批与批的一致性，每种中间体和原料药的生产工艺规程应当由一人拟定、注明日期并签名，并由质量部门的另一人独立进行检查、填写日期和签名。
6.41 Master production instructions should include:
● The name of the intermediate or API being manufactured and an identifying document reference code, if applicable
● A complete list of raw materials and intermediates designated by names or codes sufficiently specific to identify any special quality characteristics
● An accurate statement of the quantity or ratio of each raw material or intermediate to be used, including the unit of measure. Where the quantity is not fixed, the calculation for each batch size or rate of production should be included. Variations to quantities should be included where they are justified
● The production location and major production equipment to be used
● Detailed production instructions, including the:
- sequences to be followed
- ranges of process parameters to be used
- sampling instructions and in-process controls with their acceptance criteria, where appropriate
- time limits for completion of individual processing steps and/or the total process, where appropriate
- expected yield ranges at appropriate phases of processing or time
● Where appropriate, special notations and precautions to be followed, or cross-references to these
● The instructions for storage of the intermediate or API to ensure its suitability for use, including the labeling and packaging materials and special storage conditions with time limits, where appropriate. 6.41 生产工艺规程应当包括：
● 要生产的中间体或原料药的名称，如有可能，写明文件编号；
● 完整地列出原料和中间体的足以区分任何质量特性的名称或代码；
● 准确说明所用的每种原料或中间体的投料量或投料比，包括计量单位。如果投料量不是固定的，应当写明每批的批量或产率的计算方法。还应当包括经证明是合理的量的偏差；
● 生产地点及使用的主要设备；
● 详细的生产规程，包括：
- 操作顺序，
- 工艺参数的范围，
- 取样方法，过程控制及其认可标准，
- 某些情况下，要说明完成某一工序和/或整个工艺过程的时间，
- 在某一工艺阶段或时间的预期产率。
● 根据情况，写明注意事项、要遵循的预防措施，或它们的相互参照；
● 中间体或原料药的适宜贮存规定，包括标签、包装材料，某些情况下写明特殊的贮存条件、时间限制，以确保其使用。
6.5 Batch Production Records (Batch Production and Control Records) 6.5 批生产记录（批生产和控制记录）
6.50 Batch production records should be prepared for each intermediate and API and should include complete information relating to the production and control of each batch. The batch production record should be checked before issuance to ensure that it is the correct version and a legible accurate reproduction of the appropriate master production instruction. If the batch production record is produced from a separate part of the master document, that document should include a reference to the current master production instruction being used. 6.50 应当为每种中间体和原料药准备批生产记录，内容应当包括与各批生产和控制有关的完整资料。批记录发放之前，应当检查版本是否正确，是否是相应生产规程的准确明了的再现。如果批生产记录是按主文件的另一独立部分制定的，该文件应当包括对现行的生产工艺规程的参考。
6.51 These records should be numbered with a unique batch or identification number, dated and signed when issued. In continuous production, the production code together with the date and time can serve as the unique identifier until the final number is allocated. 6.51 批记录在发放时应当有一个唯一的批号或标识号，有日期和签名。连续生产时，在最终批号确定前，可以将产品代码、日期和时间结合起来作为唯一的识别符。
6.52 Documentation of completion of each significant step in the batch production records (batch production and control records) should include:
● Dates, and when appropriate, times
● Identify of major equipment (e.g., reactors, driers, mills, etc.) used
● Specific identification of each batch, including weights, measures, and batch numbers of raw materials, intermediates, or any reprocessed materials used during manufacturing
● Actual results recorded for critical process parameters
● Any sampling performed
● Signatures of the persons performing and directly supervising or checking each critical step in the operation
● In-process and laboratory test results
● Actual yield at appropriate phases or times
● Description of packaging and label for intermediate or API
● Representative label of API or intermediate if made commercially available
● Any deviation noted, its evaluation, investigation conducted (if appropriate) or reference to that investigation if stored separately
● Results of release testing 6.52 在批生产记录（批生产记录和控制记录）中提供每一重要步骤完成的证明，应当包括：
● 日期，某些情况下还有时间；
● 主要设备（如反应釜，干燥器，磨粉机等）的标识；
● 每一批的识别特征，包括原料、中间体或任何用于生产的返工物料的重量、计量单位、批号；
● 记录关键工艺参数的实际值；
● 取样；
● 每个关键步骤的操作者和直接指导者或检查者的签名；
● 过程控制和实验室的测试结果；
● 适当阶段或时间的实际产率；
● 中间体或原料药的包装材料和标签的描述；
● 原料药或中间体的商业标签的样张；
● 发现的任何偏差，进行的评估、调查（视情况而定），和索引到单独存放的调查报告；
● 放行测试的结果。
6.53 Written procedures should be established and followed for investigating critical deviations or the failure of a batch of intermediate or API to meet specifications. The investigation should extend to other batches that may have been associated with the specific failure or deviation. 6.53 应当建立并执行一种书面程序，对在符合规格上有重大偏差或不合格的一批中间体或原料药进行调查。调查还应当延伸到与这批失误或偏差有关的其它批号。
6.6 Laboratory Control Records 6.6 实验室控制记录
6.60 Laboratory control records should include complete data derived from all tests conducted to ensure compliance with established specifications and standards, including examinations and assays, as follows:
● A description of samples received for testing, including the material name or source, batch number or other distinctive code, date sample was taken, and, where appropriate, the quantity and date the sample was received for testing
● A statement of or reference to each test method used
● A statement of the weight or measure of sample used for each test as described by the method; data on or cross-reference to the preparation and testing of reference standards, reagents and standard solutions
● A complete record of all raw data generated during each test, in addition to graphs, charts and spectra from laboratory instrumentation, properly identified to show the specific material and batch tested
● A record of all calculations performed in connection with the test, including, for example, units of measure, conversion factors, and equivalency factors
● A statement of the test results and how they compare with established acceptance criteria
● The signature of the person who performed each test and the date(s) the tests were performed
● The date and signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards 6.60 实验室控制记录应当包括从为了确保符合规定的规格和标准所做的所有测试中得到的下列完整的数据，包括下列检验和测定：
● 所收到检测样品的描述，包括物料名称和来源、批号或其它编号、取样日期，某些情况下记录收到样品的量和时间；
● 每个所用检测方法的陈述或参引；
● 按方法描述的所用样品重量或计量；标准品、试剂和标准溶液的配制和测试的数据或相互参考；
● 除了正确地标明所测试的特定物料和批号的实验室仪器的图谱、图表和光谱外，还有一套从每次测试得到的所有原始数据的完整记录；
● 与测试有关的所有计算记录，包括测量单位、转换因子以及等量因子等；
● 检测结果的陈述以及与规定的认可标准的比较；
● 每项测试的操作者的签名以及测试的日期；
● 日期和第二个人的签名，表明对原记录的准确性、完整性和规定的标准的符合性已复核过。
6.61 Complete records should also be maintained for:
● Any modifications to an established analytical method
● Periodic calibration of laboratory instruments, apparatus, gauges, and recording devices
● All stability testing performed on APIs
● Out-of-specification (OOS) investigations 6.61 应当保存完整的下列记录：
● 既定的分析方法的任何修改；
● 实验室仪器、设备、仪表和记录装置的定期校验；
● 原料药的所有稳定性测试；
● 不合格的调查。
6.7 Batch Production Record Review 6.7批生产记录审核
6.70 Written procedures should be established and followed for the review and approval of batch production and laboratory control records, including packaging and labeling, to determine compliance of the intermediate or API with established specifications before a batch is released or distributed. 6.70 应当制定并执行审核和批准批生产记录和实验室控制记录，包括包装和贴签的书面程序，以便放行或分发前确定中间体或原料药是否符合规定标准。
6.71 Batch production and laboratory control records of critical process steps should be reviewed and approved by the quality unit(s) before an API batch is released or distributed. Production and laboratory control records of noncritical process steps can be reviewed by qualified production personnel or other units following procedures approved by the quality unit(s). 6.71 在一批原料药放行或分发之前，关键工序的批生产记录和实验室控制记录应当由质量部门审核和批准。非关键性工序的生产和实验室控制记录可按照经质量部门批准的程序，由有资格的生产人员或其它部门审核。
6.72 All deviation, investigation, and OOS reports should be reviewed as part of the batch record review before the batch is released. 6.72 在批放行前，所有偏差，调查和不合格报告都应当作为批记录的一部分进行审核。
6.73 The quality unit(s) can delegate to the production unit the responsibility and authority for release of intermediates, except for those shipped outside the control of the manufacturing company. 6.73 质量部门可将发放中间体的职责和权力委派给生产部门，运往生产商控制范围以外的中间体除外。
7. MATERIALS MANAGEMENT 7. 物料管理
7.1 General Controls 7.1 控制通则
7.10 There should be written procedures describing the receipt, identification, quarantine, storage, handling, sampling, testing, and approval or rejection of materials. 7.10 应当有书面程序阐明物料的接收、鉴别、待验、贮存、搬运、取样、测试和批准或拒收。
7.11 Manufacturers of intermediates and/or APIs should have a system for evaluating the suppliers of critical materials. 7.11 原料药和/或中间体生产商应当有对关键原料供应商的评估系统。
7.12 Materials should be purchased against an agreed specification, from a supplier, or suppliers, approved by the quality unit(s). 7.12 应当根据已确定的规格从经过质量部门核准的一个或多个供应商处购买物料。
7.13 If the supplier of a critical material is not the manufacturer of that material, the name and address of that manufacturer should be known by the intermediate and/or API manufacturer. 7.13 如果关键物料的供应商不是该物料的生产商，原料药或中间体的生产商应当获知该物料生产商的名称和地址。
7.14 Changing the source of supply of critical raw materials should be treated according to Section 13, Change Control. 7.14 关键原料的供应商的变更应当参照第13章“变更控制”进行。
7.2 Receipt and Quarantine 7.2接收和待验
7.20 Upon receipt and before acceptance, each container or grouping of containers of materials should be examined visually for correct labeling (including correlation between the name used by the supplier and the in-house name, if these are different), container damage, broken seals and evidence of tampering or contamination. Materials should be held under quarantine until they have been sampled, examined, or tested, as appropriate, and released for use. 7.20 一旦收到物料而尚未验收，应当目测检查物料每个或每组包装容器的标签是否正确（包括如果供应商所用名称与内部使用的名称不一致，应当检查其相互关系）、容器是否损坏、密封处和开启证据有无破裂或污染。物料应当存放的待验区，直至它们被取样、检查或酌情测试，并放行使用。
7.21 Before incoming materials are mixed with existing stocks (e.g., solvents or stocks in silos), they should be identified as correct, tested, if appropriate, and released. Procedures should be available to prevent discharging incoming materials wrongly into the existing stock. 7.21 在进厂的物料与现有的库存（如储仓中的溶剂或货物）混合之前，应当确认货是否对、必要时进行测试并放行。应当有程序来防止把来料错放到现有的库存中。
7.22 If bulk deliveries are made in nondedicated tankers, there should be assurance of no cross-contamination from the tanker. Means of providing this assurance could include one or more of the following:
● certificate of cleaning
● testing for trace impurities
● audit of the supplier 7.22 对于非专用槽车运送的大宗物料，应当确保没有来自槽车的交叉污染。可用以下的一种或几种方法来提供这种保证：
● 清洁证书
● 残留物的测试
● 供应商审计
7.23 Large storage containers and their attendant manifolds, filling, and discharge lines should be appropriately identified. 7.23 大的储存容器及其随附的管路、填充和排放管都应当适当标明。
7.24 Each container or grouping of containers (batches) of materials should be assigned and identified with a distinctive code, batch, or receipt number. This number should be used in recording the disposition of each batch. A system should be in place to identify the status of each batch. 7.24 每个或每组物料容器（几批）的物料都应当指定并标上编号、批号或接收号。此号码应当用于记录每批的处置情况。应当有一个识别每批状态的系统。
7.3 Sampling and Testing of Incoming Production Materials 7.3 进厂物料的取样与测试
7.30 At least one test to verify the identity of each batch of material should be conducted, with the exception of the materials described below. A supplier’s certificate of analysis can be used in place of performing other tests, provided that the manufacturer has a system in place to evaluate suppliers. 7.30 除了7.32中指出的物料，对于每批物料至少要做一个鉴别试验。在生产商对供应商有一套审计体系的前提下，供应商的分析报告可以用来替代其他项目的测试。
7.31 Supplier approval should include an evaluation that provides adequate evidence (e.g., past quality history) that the manufacturer can consistently provide material meeting specifications. Complete analyses should be conducted on at least three batches before reducing in-house testing. However, as a minimum, a complete analysis should be performed at appropriate intervals and compared with the certificates of analysis. Reliability of certificates of analysis should be checked at regular intervals. 7.31 对供应商的核准应当包括一次评估，提供足够的证据（如过去的质量记录）证明该生产商始终都能提供符合质量标准的物料。在减少内部测试之前至少应当对三批物料作全检。然而，最低限度每隔一定时间应当进行一次全检，并与分析报告进行比较。分析报告的可靠性应当定期进行检查。
7.32 Processing aids, hazardous or highly toxic raw materials, other special materials, or materials transferred to another unit within the company’s control do not need to be tested if the manufacturer’s certificate of analysis is obtained, showing that these raw materials conform to established specifications. Visual examination of containers, labels, and recording of batch numbers should help in establishing the identity of these materials. The lack of on-site testing for these materials should be justified and documented. 7.32 工艺助剂、有害或剧毒的原料、其它特殊物料、或转移到公司控制范围内的另一个部门的物料不用测试，前提是能取得生产商的分析报告，证明这些原料符合规定的质量标准。对容器、标签和批号记录进行目测检查应当有助于鉴别这些原料。对这些物料不作现场测试应当说明理由，并用文件证明。
7.33 Samples should be representative of the batch of material from which they are taken. Sampling methods should specify the number of containers to be sampled, which part of the container to sample, and the amount of material to be taken from each container. The number of containers to sample and the sample size should be based on a sampling plan that takes into consideration the criticality of the material, material variability, past quality history of the supplier, and the quality needed for analysis. 7.33 取样应当能代表被取的那批物料。取样方法应当规定：取样的容器数，取样部位，每个容器的取样量。取样容器数和取样量应当根据取样方案来决定。取样方案的制定要综合考虑物料的重要程度、变异性、供应商过去的质量情况，以及分析需用量。
7.34 Sampling should be conducted at defined locations and by procedures designed to prevent contamination of the material sampled and contamination of other materials. 7.34 应当在规定的地点，用规定的方法取样，以避免取样的物料被污染，或污染其它物料。
7.35 Containers from which samples are withdrawn should be opened carefully and subsequently reclosed. They should be marked to indicate that a sample has been taken. 7.35 被取样的容器应当小心开启，随后重新密封。这些容器应当做标记表明样品已抽取。
7.4 Storage 7.4储存
7.40 Materials should be handled and stored in a manner to prevent degradation, contamination, and cross-contamination. 7.40 物料的搬运和贮存应当防止降解、污染和交叉污染。
7.41 Materials stored in fiber drums, bags, or boxes should be stored off the floor and, when appropriate, suitably spaced to permit cleaning and inspection. 7.41 纤维板桶、袋子或盒装物料应当离地贮存，并根据情况留出适当空间便于清洁和检查。
7.42 Materials should be stored under conditions and for a period that have no adverse effect on their quality, and should normally be controlled so that the oldest stock is used first. 7.42 物料应当在对其质量没有不良影响的条件下和时限内贮存，而且通常应当加以控制，做到先进先出。
7.43 Certain materials in suitable containers can be stored outdoors, provided identifying labels remain legible and containers are appropriately cleaned before opening and use. 7.43 某些装在适当容器中的物料可以存放在室外，只要识别标签保持清晰，而且容器在开启和使用前进行适当清洁。
7.44 Rejected materials should be identified and controlled under a quarantine system designed to prevent their unauthorized use in manufacturing. 7.44 不合格物料应当做标识，并用隔离系统控制，已防止未经许可而用于生产。
7.5 Re-evaluation 7.5重新评估
7.50 Materials should be re-evaluated, as appropriate, to determine their suitability for use (e.g., after prolonged storage or exposure to heat or humidity). 7.50 应当根据情况对物料进行重新评估以便确定其使用的适合性（例如长期存放或暴露于热或潮湿的环境中）。
8. PRODUCTION AND IN-PROCESS CONTROLS 8. 生产和过程控制
8.1 Production Operations 8.1 生产操作
8.10 Raw materials for intermediate and API manufacturing should be weighed or measured under appropriate conditions that do not affect their suitability for use. Weighing and measuring devices should be of suitable accuracy for the intended use. 8.10 用于生产中间体和原料药的原料应当在适宜的条件下称重或测量，以便不影响其使用的适合性。称重和测量装置应当有适合于其用途的精度。
8.11 If a material is subdivided for later use in production operations, the container receiving the material should be suitable and should be so identified that the following information is available:
● Material name and/or item code
● Receiving or control number
● Weight or measure of material in the new container
● Re-evaluation or retest date if appropriate 8.11 如果某物料分出一部分留待以后的生产操作中使用，应当用适合的容器来盛装该物料，并应当标明下列信息：
● 物料的名称和/或货号；
● 接收号或控制号；
● 新容器中物料的重量或计量；
● 如有必要，标明复验期。
8.12 Critical weighing, measuring, or subdividing operations should be witnessed or subjected to an equivalent control. Prior to use, production personnel should verify that the materials are those specified in the batch record for the intended intermediate or API. 8.12 关键的称重、测量或分装操作应当有人作证或接受相应的控制。使用前，生产人员应当确认该物料是要生产的中间体或原料药的批记录中指定的。
8.13 Other critical activities should be witnessed or subjected to an equivalent control. 8.13 其它关键活动应当有人作证或接受相应的控制。
8.14 Actual yields should be compared with expected yields at designated steps in the production process. Expected yields with appropriate ranges should be established based on previous laboratory, pilot scale, or manufacturing data. Deviations in yield associated with critical process steps should be investigated to determine their impact or potential impact on the resulting quality of affected batches. 8.14 在生产过程中的指定步骤，实际收率应当与预计的收率作比较。具有合适范围的预计收率应当根据以前的实验室、中试规模或生产的数据来确定。应当调查与关键工艺步骤有关的收率偏差，以确定其对相关批号最终质量的影响或潜在影响。
8.15 Any deviation should be documented and explained. Any critical deviation should be investigated. 8.15 任何偏差都应当记录，并作解释。任何关键的偏差应当作调查。
8.16 The processing status of major units of equipment should be indicated either on the individual units of equipment or by appropriate documentation, computer control systems, or alternative means. 8.16 应当标明主要设备的生产状态，可以标在每个设备上，或者用文件、计算机控制系统或其它替代的方法。
8.17 Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized use. 8.17 对需要进行返工或重新加工的物料应当适当地加以控制，防止未经许可就使用。
8.2 Time Limits 8.2 时限
8.20 If time limits are specified in the master production instruction (see 6.40), these time limits should be met to ensure the quality of intermediates or APIs. Deviations should be documented and evaluated. Time limits may be inappropriate when processing to a target value (e.g., pH adjustment, hydrogenation, drying to predetermined specification) because completion of reactions or processing steps are determined by in-process sampling and testing. 8.20 如果生产工艺规程（见6.40）中规定了时限，应当遵守这些时限，以保证中间体和原料药的质量。所有偏差都要有记录并解释原因。在加工到一个目标值时（例如，调节pH、氢化、干燥到预定标准），时限可能就不合适了，因为反应或加工步骤的完成是取决于过程中的取样和测试的。
8.21 Intermediates held for further processing should be stored under appropriate conditions to ensure their suitability for use. 8.21 留作进一步加工的中间体应当在适宜的条件下储存，以保证其适宜于使用。
8.3 In-process Sampling and Controls 8.3 工序间的取样和控制
8.30 Written procedures should be established to monitor the progress and control the performance of processing steps that cause variability in the quality characteristics of intermediates and APIs. In-process controls and their acceptance criteria should be defined based on the information gained during the developmental stage or from historical data. 8.30 应当制定书面程序来监测会造成中间体和原料药质量特性变异的工艺步骤的进程，并控制其生产情况。工序间控制及其接受标准应当根据项目开发阶段或者以往的生产数据来确定。
8.31 The acceptance criteria and type and extent of testing can depend on the nature of the intermediate or API being manufactured, the reaction or process step being conducted, and the degree to which the process introduces variability in the product’s quality. Less stringent in-process controls may be appropriate in early processing steps, whereas tighter controls may be appropriate for later processing steps (e.g., isolation and purification steps). 8.31 综合考虑所生产中间体和原料药的特性，反应类型，该工序对产品质量影响的程度大小等因素来确定可接受的标准，检测类型和范围。前期生产的中间体控制标准可以松一些，越接近成品，中间控制的标准越严（如分离，纯化）。
8.32 Critical in-process controls (and critical process monitoring), including control points and methods, should be stated in writing and approved by the quality unit(s). 8.32 关键的中间控制（和工艺监测），包括控制点和方法，应当书面规定，并经质量部门批准。
8.33 In-process controls can be performed by qualified production department personnel and the process adjusted without prior quality unit(s) approval if the adjustments are made within pre-established limits approved by the quality unit(s). All test and results should be fully documented as part of the batch record. 8.33 中间控制可以由合格的生产部门的人员来进行，而调节的工艺可以事先未经质量部门批准，只要该调节在由质量部门批准的预先规定的限度以内。所有测试及结果都应当作为批记录的一部分全部归档。
8.34 Written procedures should describe the sampling methods for in-process materials, intermediates, and APIs. Sampling plans and procedures should be based on scientifically sound sampling practices. 8.34 应当制定书面程序，说明中间物料、中间体和原料药的取样方法。取样方案和程序应当基于科学合理的取样实践。
8.35 In-process sampling should be conducted using procedures designed to prevent contamination of the sampled material and other intermediates or APIs. Procedures should be established to ensure the integrity of samples after collection. 8.35 工序间取样应当按能防止污染所取的样品、其它中间体或原料药的程序进行。应当制定保证样品收集后的完整性的程序。
8.36 Out-of-specification (OOS) investigations are not normally needed for in-process tests that are performed for the purpose of monitoring and/or adjusting the process. 8.36 生产操作中的正常监控过程和工艺调节过程中出现的超出标准的偏差（OOS），通常情况不需要调查。
8.4 Blending Batches of Intermediates or APIs 8.4 中间体或原料药的混批
8.40 For the purpose of this document, blending is defined as the process of combining materials within the same specification to produce a homogeneous intermediate or API. In-process mixing of fractions from single batches (e.g., collecting several centrifuge loads from a single crystallization batch) or combining fractions from several batches for further processing is considered to be part of the production process and is not considered to be blending. 8.40 根据本文件的目的，混合的定义是为了生产出均匀的中间体或原料药而将同一质量标准的物料混在一起的过程。同一批号几部分（例如，收集一个结晶批号出来的几次离心机装的料）的工艺间的混合，或者混合从几个批号来的部分作进一步加工，看作是生产工艺的一部分，而不是混合。
8.41 Out-of-specification batches should not be blended with other batches for the purpose of meeting specifications. Each batch incorporated into the blend should have been manufactured using an established process and should have been individually tested and found to meet appropriate specifications prior to blending. 8.41 不合格的批号不能与其他批号混合在一起来达到符合质量标准的目的。混合的每一个批号都应该是用规定的生产工艺生产的，混合前应当单独检测，并符合相应的质量标准。
8.42 Acceptable blending operations include, but are not limited to:
● Blending of small batches to increase batch size
● Blending of tailings (i.e., relatively small quantities of isolated material) from batches of the same intermediate or API to form a single batch 8.42 可接受的混合操作包括但不限于：
● 将小批混合，增大批量；
● 将多批同一中间体或原料药的尾料（例如，分离出的相对较少的量）混合成为一个批号。
8.43 Blending processes should be adequately controlled and documented, and the blended batch should be tested for conformance to established specifications, where appropriate. 8.43 混合过程应当充分控制并记录，混合后的批号应当根据情况进行测试，以确认是否达到质量标准。
8.44 The batch record of the blending process should allow traceability back to the individual batches that make up the blend. 8.44 混合过程的批记录应当允许追溯到参与混合的每个单独批号。
8.45 Where physical attributes of the API are critical (e.g., APIs intended for use in solid oral dosage forms or suspensions), blending operations should be validated to show homogeneity of the combined batch. Validation should include testing of critical attributes (e.g., particle size distribution, bulk density, and tap density) that may be affected by the blending process. 8.45 如果原料药的物理性质至关重要（例如，用于固体口服制剂或混悬剂的原料药），混合工艺应当验证，以显示混合后批号的均匀性。验证应当包括测试可能受混合过程影响的关键属性（例如，粒度分布，堆密度和振实密度）。
8.46 If the blending could adversely affect stability, stability testing of the final blended batches should be performed. 8.46 如果混合会对稳定性有不良影响，应当对最终混合批号进行稳定性测试。
8.47 The expiry or retest date of the blended batch should be based on the manufacturing date of the oldest tailings or batch in the blend. 8.47 混合批号的有效期或复验期应当以混合中生产日期最早的尾料或批次的批号为基准。
8.5 Contamination Control 8.5 污染控制
8.50 Residual materials can be carried over into successive batches of the same intermediate or API if there is adequate control. Examples include residue adhering to the wall of a micronizer, residual layer of damp crystals remaining in a centrifuge bowl after discharge, and incomplete discharge of fluids or crystals from a processing vessel upon transfer of the material to the next step in the process. Such carryover should not result in the carryover of degradants or microbial contamination that may adversely alter the established API impurity profile. 8.50 在得到充分控制的前提下，上一批号的同一中间体或原料药的剩余物可以带入下几个连续批号。例如，黏附在微粉机壁上的残留，离心出料后残留在离心机筒体内的潮湿的结晶，将物料转至下一步工序时无法从反应器中彻底放尽的物料。此类带入不应当导致因带入降解物或微生物的污染而对已经建立的原料药杂质概况有不良影响。
8.51 Production operations should be conducted in a manner that prevents contamination of intermediates or APIs by other materials. 8.51 生产操作应当防止中间体或原料药被其它物料污染。
8.52 Precautions to avoid contamination should be taken when APIs are handled after purification. 8.52 处理精制后的原料药应当采取预防污染的措施。
9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES 9. 原料药和中间体的包装和贴签
9.1 General 9.1 总则
9.10 There should be written procedures describing the receipt, identification, quarantine, sampling, examination, and/or testing, release, and handling of packaging and labeling materials. 9.10 应当有书面程序描述包装和贴签用物料的接收、鉴别、待验、取样、检查和/或测试、放行和搬运。
9.11 Packaging and labeling materials should conform to established specifications. Those that do not comply with such specifications should be rejected to prevent their use in operations for which they are unsuitable. 9.11 包装和贴签用物料应当符合规定的质量标准。不合格者要拒收，不得用于不适合于其的操作中。
9.12 Records should be maintained for each shipment of labels and packaging materials showing receipt, examination, or testing, and whether accepted or rejected. 9.12 每次运来的标签和包装材料应当有接收、检查或测试、以及合格还是拒收的记录。
9.2 Packaging Materials 9.2 包装材料
9.20 Containers should provide adequate protection against deterioration or contamination of the intermediate or API that may occur during transportation and recommended storage. 9.20 容器应当能够对中间体和原料药提供足够的保护，使其在运输和建议的贮存条件下不会变质或受到污染。
9.21 Containers should be clean and, where indicated by the nature of the intermediate or API, sanitized to ensure that they are suitable for their intended use. These containers should not be reactive, additive, or absorptive so as to alter the quality of the intermediate or API beyond the specified limits. 9.21 容器应当清洁，如果中间体或原料药有要求时，应当进行消毒，以确保适合于其预期的用途。这些容器应无反应活性、加和性或吸附性，一面改变中间体或原料药的质量使其超出质量标准的限度。
9.22 If containers are reused, they should be cleaned in accordance with documented procedures, and all previous labels should be removed or defaced. 9.22 容器被重新使用时，应当按照规定程序进行清洁，并出去或涂毁以前的所有标签。
9.3 Label Issuance and Control 9.3 标签发放与控制
9.30 Access to the label storage areas should be limited to authorized personnel. 9.30 只有获准人员才能进入标签贮存区。
9.31 Procedures should be established to reconcile the quantities of labels issued, used, and returned and to evaluate discrepancies found between the number of containers labeled and the number of labels issued. Such discrepancies should be investigated, and the investigation should be approved by the quality unit(s). 9.31 应当建立规程来平衡发出的、使用的和退回的标签的数量，并评估已贴签的容器数和发出的标签数之间的偏差值。此种差异应当加以调查，调查应当由质量保证部门批准。
9.32 All excess labels bearing batch numbers or other batch-related printing should be destroyed. Returned labels should be maintained and stored in a manner that prevents mix-ups and provides proper identification. 9.32 所有剩余的印有批号或与批有关内容的标签都应当销毁。收回的标签应当以防止混淆并提供适当标识的方式加以保留和贮存。
9.33 Obsolete and out-dated labels should be destroyed. 9.33 废弃的和过期的标签应当销毁。
9.34 Printing devices used to print labels for packaging operations should be controlled to ensure that all imprinting conforms to the print specified in the batch production record. 9.34 包装操作中用于印刷标签的印刷设备应当加以监控，以确保所有印刷内容符合批生产记录中的内容。
9.35 Printed labels issued for a batch should be carefully examined for proper identity and conformity to specifications in the master production record. The results of this examination should be documented. 9.35 应当仔细检查发放给某批的打印好的标签，其标识是否正确，并符合主生产记录的内容。检查结果应当记录在批生产记录中。
9.36 A printed label representative of those used should be included in the batch production record. 9.36 批生产记录中应当附一张代表那些所用标签的印制好的标签。
9.4 Packaging and Labeling Operations 9.4 包装和贴签操作
9.40 There should be documented procedures designed to ensure that correct packaging materials and labels are used. 9.40 应当有文件化的规程确保使用正确的包装材料和标签。
9.41 Labeling operations should be designed to prevent mix-ups. There should be physical or spatial separation from operations involving other intermediates or APIs. 9.41 帖签操作应当防止混淆。应当与涉及其它中间体或原料药的操作有物理的或空间的隔离。
9.42 Labels used on containers of intermediates or APIs should indicate the name or identifying code, batch number, and storage conditions when such information is critical to ensure the quality of intermediate or API. 9.42 用于中间体或原料药容器的标签应当注明：确保中间体或原料药质量的关键信息，如名称、识别代码、产品批号和储存条件。
9.43 If the intermediate or API is intended to be transferred outside the control of the manufacturer’s material management system, the name and address of the manufacturer, quantity of contents, special transport conditions, and any special legal requirements should also be included on the label. For intermediates or APIs with an expiry date, the expiry date should be indicated on the label and certificate of analysis. For intermediates or APIs with a retest date, the retest date should be indicated on the label and/or certificate of analysis. 9.43 如果中间体或原料药要向生产商的物料管理系统控制范围以外运输，标签上还应当包括生产商的名称、地址，装量，特殊的运输要求，和其它特殊的法定要求。对于有失效期的中间体或原料药，标签和分析报告单上应当注明失效期。对于有复验期的中间体或原料药，标签和/或分析报告单上应当注明复验期。
9.44 Packaging and labeling facilities should be inspected immediately before use to ensure that all materials not needed for the next packaging operation have been removed. This examination should be documented in the batch production records, the facility log, or other documentation system. 9.44 包装和帖签设施应当在使用前进行检查，以确定下一次包装操作不需要的所有物料都已清除。该检查应当记录在批生产记录、设备使用记录或其它文件系统中。
9.45 Packaged and labeled intermediates or APIs should be examined to ensure that containers and packages in the batch have the correct label. This examination should be part of the packaging operation. Results of these examinations should be recorded in the batch production or control records. 9.45 应当检查已包装和帖签的中间体或原料药，以确保该批的容器和包装的标签正确。该检查应当作为包装操作的一部分。检查结果应当记录在批生产或控制记录中。
9.46 Intermediate or API containers that are transported outside of the manufacturer’s control should be sealed in a manner such that, if the seal is breached or missing, the recipient will be alerted to the possibility that the contents may have been altered. 9.46需向生产商的物料管理系统控制范围以外运输的中间体或原料药的容器应当用一种密封形式，以至于一旦密封破损或遗失，收货者会留意到其内容物有可能被动过。
10. STORAGE AND DISTRIBUTION 10.储存和分发
10.1 Warehousing Procedures 10.1 入库程序
10.10 Facilities should be available for the storage of all materials under appropriate conditions (e.g., controlled temperature and humidity when necessary). Records should be maintained of these conditions if they are critical for the maintenance of material characteristics. 10.10 应当提供在适当条件下（需要时控制温度和湿度）贮存所有物料的设施。应当记录对保持物料特性至关重要的贮存条件。
10.11 Unless there is an alternative system to prevent the unintentional or unauthorized use of quarantined, rejected, returned, or recalled materials, separate storage areas should be assigned for their temporary storage until the decision as to their future use has been made. 10.11 除非另有其它系统可以防止待验的、不合格的退回或召回的物料的误用或未经许可擅自使用，应当为其临时存放指定单独的存放区域，直至其今后用途确定为止。
10.2 Distribution Procedures 10.2 分发程序
10.20 APIs and intermediates should only be released for distribution to third parties after they have been released by the quality unit(s). APIs and intermediates can be transferred under quarantine to another unit under the company’s control when authorized by the quality unit(s) and if appropriate controls and documentation are in place. 10.20 原料药和中间体经质量部门放行后才能分发给第三方。经质量部门授权，而且如果有合适的控制并有文件证明，可允许待验的原料药和中间体在公司的控制范围下，转移到另一部门。
10.21 APIs and intermediates should be transported in a manner that does not adversely affect their quality. 10.21 原料药和中间体应当以对其质量不产生负面影响的方式运输。
10.22 Special transport or storage conditions for an API or intermediate should be stated on the label. 10.22 原料药或中间体的特殊运输或贮存条件应当在标签上注明。
10.23 The manufacturer should ensure that the contract acceptor (contractor) for transportation of the API or intermediate knows and follows the appropriate transport and storage conditions. 10.23 生产商应当确保运输原料药或中间体的合同接受方（订约人）了解并遵从相关的运输和贮存条件。
10.24 A system should be in place by which the distribution of each batch of intermediate and/or API can be readily determined to permit its recall. 10.24 应当建立一个系统，可用它来对每批中间体和/或原料药的分发随时决定召回。
11. LABORATORY CONTROLS 11.实验室控制
11.1 General Controls 11.1 控制通则
11.10 The independent quality unit(s) should have at its disposal adequate laboratory facilities. 11.10 独立的质量部门应当有受其支配的、足够的实验室设施。
11.11 There should be documented procedures describing sampling, testing, approval, or rejection of materials and recording and storage of laboratory data. Laboratory records should be maintained in accordance with Section 6.6. 11.11 应当备有阐述物料取样、测试、物料批准或拒收，和实验室的记录及保存的书面程序。实验室记录应当按照6.6节中所述要求保存。
11.12 All specifications, sampling plans, and test procedures should be scientifically sound and appropriate to ensure that raw materials, intermediates, APIs, and labels and packaging materials conform to established standards of quality and/or purity. Specifications and test procedures should be consistent with those included in the registration/filing. There can be specifications in addition to those in the registration/filing. Specifications, sampling plans, and test procedures, including changes to them, should be drafted by the appropriate organizational unit and reviewed and approved by the quality unit(s). 11.12 所有的质量标准，取样方案和测试程序都应当科学合理并适当，以确保原料、中间体、原料药，标签和包装材料能达到规定的质量和/或纯度标准。质量标准和测试方法应当与注册/申报中的一致。可以有注册/申报以外的附加的质量标准。质量标准、取样方案和测试程序，包括相应的变更，应当由相关的组织机构起草，并由质量部门审核、批准。
11.13 Appropriate specifications should be established for APIs in accordance with accepted standards and consistent with the manufacturing process. The specifications should include control of impurities (e.g., organic impurities, inorganic impurities, and residual solvents). If the API has a specification for microbiological purity, appropriate action limits for total microbial counts and objectionable organisms should be established and met. If the API has a specification for endotoxins, appropriate action limits should be established and met. 11.13 应当根据已接受的标准和与生产工艺的一致性来制订合适的原料药质量标准。质量标准应当包括对杂质的控制（如有机杂质、无机杂质，和残留溶剂）。如果原料药有微生物纯度的质量规格，应当制订并达到合适的总菌落数和致病菌的处置限度。如果原料药有内毒素的质量规格，应当制订并达到合适的内毒素的处置限度。
11.14 Laboratory controls should be followed and documented at the time of performance. Any departures from the above-described procedures should be documented and explained. 11.14 应当遵守实验室控制，并边操作边记录。对上述程序的任何偏离都应当有记录并作解释。
11.15 Any out-of-specification result obtained should be investigated and documented according to a procedure. This procedure should include analysis of the data, assessment of whether a significant problem exists, allocation of the tasks for corrective actions, and conclusions. Any resampling and/or retesting after OOS results should be performed according to a documented procedure. 11.15 得到的任何不符合质量标准的结果都应当按照程序进行调查，并备案。该程序应当要求对数据进行分析，评价是否有值得注意的问题存在，分配整改措施的任务和结论。发现不符合质量标准的结果后，任何重新取样和/或重新测试都应当按照成文的程序进行。
11.16 Reagents and standard solutions should be prepared and labeled following written procedures. Use by dates should be applied, as appropriate, for analytical reagents or standard solutions. 11.16 应当按照书面程序来配制试剂和标准溶液以及贴标签。分析试剂或标准溶液应当酌情采用“用至”日期。
11.17 Primary reference standards should be obtained, as appropriate, for the manufacture of APIs. The source of each primary reference standard should be documented. Records should be maintained of each primary reference standard’s storage and use in accordance with the supplier’s recommendations. Primary reference standards obtained from an officially recognized source are normally used without testing if stored under conditions consistent with the supplier’s recommendations. 11.17 原料药生产时应当酌情获得合适的基本参考标准品。每一个基本参考标准品的来源要备案。应根据标准品供应商的要求进行标准品的储存和使用，并进行相应记录同时保存记录。对于从官方认可的渠道获得的基本参考标准品，在按照供应商的建议的保存条件进行保存的情况下，通常无需检验就可以使用。
11.18 Where a primary reference standard is not available from an officially recognized source, an in-house primary standard should be established. Appropriate testing should be performed to establish fully the identity and purity of the primary reference standard. Appropriate documentation of this testing should be maintained. 11.18 从官方认可的货源处无法得到基本参考标准品时，应该制备一个“内部基本标准品”。应当做合适的测试来全面制订该基本参考标准品的鉴别和纯度。该测试的相关证明文件应当保留。
11.19 Secondary reference standards should be appropriately prepared, identified, tested, approved, and stored. The suitability of each batch of secondary reference standard should be determined prior to first use by comparing against a primary reference standard. Each batch of secondary reference standard should be periodically requalified in accordance with a written protocol. 11.19 二级参考标准品应当用合适的方法来制备，鉴别，测试，批准和储存。每一批二级参考标准品在第一次使用前，应当与基本参考标准品进行比较，来确定其适用性。每一批二级参考标准品应当根据书面方案，定期进行重新确认。
11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的测试
11.20 For each batch of intermediate and API, appropriate laboratory tests should be conducted to determine conformance to specifications. 11.20 每一批中间体和原料药都应当进行适当的实验室测试，以确定是否符合质量标准。
11.21 An impurity profile describing the identified and unidentified impurities present in a typical batch produced by a specific controlled production process should normally be established for each API. The impurity profile should include the identity or some qualitative analytical designation (e.g., retention time), the range of each impurity observed, and classification of each identified impurity (e.g., inorganic, organic, solvent). The impurity profile is normally dependent upon the production process and origin of the API. Impurity profiles are normally not necessary for APIs from herbal or animal tissue origin. Biotechnology considerations are covered in ICH guidance Q6B. 11.21 每一种原料药都应当有杂质概况，描述用一特别控制的生产工艺生产出的典型批号中存在的已确定和未确定的杂质。杂质概况应当包括观测到的每一个杂质的鉴别或某个定量分析的标志（如保留时间）、范围，以及已确定杂质的类别（如有机的、无机的、溶剂）。杂质概况一般与原料药的生产工艺和起源有关。从植物或动物组织中得到的原料药通常不一定要有杂质概况。ICH指南Q6B讲述了对生物技术的考虑。
11.22 The impurity profile should be compared at appropriate intervals against the impurity profile in the regulatory submission or compared against historical data to detect changes to the API resulting from modifications in raw materials, equipment operating parameters, or the production process. 11.22 每隔一端时间应当将杂质概况与药政申报中的杂质概况，或与以往的数据比较，以查明原材料、设备操作参数和生产工艺的修改所造成的原料药的变化。
11.23 Appropriate microbiological tests should be conducted on each batch of intermediate and API where microbial quality is specified. 11.23 在规定微生物质量时，应当对每一批中间体和原料药作适当的微生物测试。
11.3 Validation of Analytical Procedures 11.3 分析方法的验证
See Section 12. 见第12章
11.4 Certificates of Analysis 11.4 分析报告单
11.40 Authentic certificates of analysis should be issued for each batch of intermediate or API on request. 11.40 有要求时应当为每一批中间体或原料药出具可信的分析报告单。
11.41 Information on the name of the intermediate or API including, where appropriate, its grade, the batch number, and the date of release should be provided on the certificate of analysis. For intermediates or APIs with an expiry date, the expiry date should be provided on the label and certificate of analysis. For intermediates or APIs with a retest date, the retest date should be indicated on the label and/or certificate of analysis. 11.41 分析报告单应当提供中间体或原料药的名称，必要时包括其等级、批号和放行日期。有有效期的中间体或原料药，应当在标签和分析报告单上提供失效期。有复验期的中间体或原料药，应当在标签和/或分析报告单上提供复验期。
11.42 The certificate should list each test performed in accordance with compendial or customer requirements, including the acceptance limits, and the numerical results obtained (if test results are numerical). 11.42 报告单应当列明按药典或客户要求所做的各项测试，包括可接受的限度，和得到的数值结果（如果测试结果是数值）。
11.43 Certificates should be dated and signed by authorized personnel of the quality unit(s) and should show the name, address, and telephone number of the original manufacturer. Where the analysis has been carried out by a repacker or reprocessor, the certificate of analysis should show the name, address, and telephone number of the repacker/reprocessor and reference the name of the original manufacturer. 11.43 报告单应当由指定的质量部门人员写明日期并签名，而且应当注明原生产商的名称、地址和电话。如果测试是由重新包装者或重新加工者做的，则分析报告单应当注明重新包装者/重新加工者的名称、地址和电话，并附注原生产商的名称。
11.44 If new certificates are issued by or on behalf of repackers/reprocessors, agents or brokers, these certificates should show the name, address, and telephone number of the laboratory that performed the analysis. They should also contain a reference to the name and address of the original manufacturer and to the original batch certificate, a copy of which should be attached. 11.44 如果由重新包装者/重新加工者、代理人，中间人或由其代表出具新的报告单，这些报告单上应当注明做分析的实验室的名称、地址和电话。还应当附注原生产商的名称和地址，并附上原始检验报告单复印件。
11.5 Stability Monitoring of APIs 11.5 原料药的稳定性监测
11.50 A documented, on-going testing program should be established to monitor the stability characteristics of APIs, and the results should be used to confirm appropriate storage conditions and retest or expiry dates. 11.50 应当建立一个文件化的、持续监测的规程，以监测原料药的稳定性特征，而其结果应当用于确定适当的贮存条件和复验日期或有效期。
11.51 The test procedures used in stability testing should be validated and be stability indicating. 11.51 用于稳定性测试的测试规程应当经过验证，并能显示稳定性。
11.52 Stability samples should be stored in containers that simulate the market container. For example, if the API is marketed in bags within fiber drums, stability samples can be packaged in bags of the same material and in small-scale drums of similar or identical material composition to the market drums. 11.52 稳定性样品应当存放在与销售容器相仿的容器中。例如，如果原料药是装在纤维桶内的袋子里销售的，稳定性样品可以包装在同样材料的袋中，放入相似或相同与销售容器的材料的材料较小的桶中。
11.53 Normally, the first three commercial production batches should be placed on the stability monitoring program to confirm the retest or expiry date. However, where data from previous studies show that the API is expected to remain stable for at least 2 years, fewer than three batches can be used. 11.53 通常头三个销售批号应当放入稳定性监测计划，以证实复验期或有效期。然而，如果以前的研究数据表明原料药至少在两年内可望保持稳定，则所用的批号可少于三批。
11.54 Thereafter, at least one batch per year of API manufactured (unless none is produced that year) should be added to the stability monitoring program and tested at least annually to confirm the stability. 11.54 以后每年至少应当加一批生产的原料药到稳定性监测计划（除非当年不生产），并且至少每年测试，以证实其稳定性。
11.55 For APIs with short shelf-lives, testing should be done more frequently. For example, for those biotechnological/biologic and other APIs with shelf-lives of one year or less, stability samples should be obtained and should be tested monthly for the first three months, and at 3-month intervals after that. When data exist that confirm that the stability of the API is not compromised, elimination of specific test intervals (e.g., 9-month testing) can be considered. 11.55 对于储存期较短的原料药，应当更频繁的测试。例如，储存期不超过一年的生物工程/生物制品或其它原料药，应当有稳定性样品，头三个月内应当每月测试，随后每三个月测试一次。如果有数据表明原料药的稳定性不会受影响，可以考取消特定的测试间隔（如9个月的测试）。
11.56 Where appropriate, the stability storage conditions should be consistent with the ICH guidances on stability. 11.56 根据情况，稳定性储存条件应当与ICH的稳定性指南一致。
11.6 Expiry and Retest Dating 11.6 有效期和复验期
11.60 When an intermediate is intended to be transferred outside the control of the manufacturer’s material management system and an expiry or retest date is assigned, supporting stability information should be available (e.g., published data, test results). 11.60 当一个中间体要运送到生产商物料管理系统控制范围以外，并已制定了有效期或复验期时，那就应当有支持的稳定性信息（如发表的数据、测试结果）。
11.61 An API expiry or retest date should be based on an evaluation of data derived from stability studies. Common practice is to use a retest date, not an expiration date. 11.61 一种原料药的有效期或复验期应当基于稳定性研究所得数据的评估。通常会用复验期，而不用有效期。
11.62 Preliminary API expiry or retest dates can be based on pilot scale batches if (1) the pilot batches employ a method of manufacture and procedure that simulates the final process to be used on a commercial manufacturing scale and (2) the quality of the API represents the material to be made on a commercial scale. 11.62 如果（1）中试批号采用的生产方法和规程是模拟用于商业生产规模的最终工艺，而且（2）原料药的质量代表了商业生产规模的物料，则原料药的初步有效期或复验期可基于中试规模的批号。
11.63 A representative sample should be taken for the purpose of performing a retest. 11.63 应当取一个具有代表性的样品进行复验。
11.7 Reserve/Retention Samples 11.7 留样
11.70 The packaging and holding of reserve samples is for the purpose of potential future evaluation of the quality of batches of API and not for future stability testing purposes. 11.70 留样的包装和储存是为了今后可能会对原料药批号的质量进行评价，而不是以将来的稳定性测试为目的的。
11.71 Appropriately identified reserve samples of each API batch should be retained for 1 year after the expiry date of the batch assigned by the manufacturer, or for 3 years after distribution of the batch, whichever is longer. For APIs with retest dates, similar reserve samples should be retained for 3 years after the batch is completely distributed by the manufacturer. 11.71 适当标识的每一批原料药的留样应当保留到由生产商规定的该批号的有效期满后一年，或该批产品销售后三年，以较长时间为准。对于有复验期的原料药，相似的留样应当保留到生产商全部销售完该批号后三年。
11.72 The reserve sample should be stored in the same packaging system in which the API is stored or in one that is equivalent to or more protective than the marketed packaging system. Sufficient quantities should be retained to conduct at least two full compendial analyses or, when there is no pharmacopoeial monograph, two full specification analyses. 11.72 留样应当储存在原料药储存的同样的包装系统中，或者与销售包装相同，或更具保护性。应当留足够的量来至少做两次法定的全检，或者没有药典专论时，两次质量标准的全检。
12. VALIDATION 12.验证
12.1 Validation Policy 12.1 验证方针
12.10 The company’s overall policy, intentions, and approach to validation, including the validation of production processes, cleaning procedures, analytical methods, in-process control test procedures, computerized systems, and persons responsible for design, review, approval, and documentation of each validation phase, should be documented. 12.10 公司的总体验证原则、目的和方法，包括生产工艺、清洁规程、分析方法、过程控制测试规程以及计算机系统的验证和负责设计、审核、批准和为各个验证阶段提供证明文件的人员都应当明文规定。
12.11 The critical parameters/attributes should normally be identified during the development stage or from historical data, and the necessary ranges for the reproducible operation should be defined. This should include:
● Defining the API in terms of its critical product attributes
● Identifying process parameters that could affect the critical quality attributes of the API
● Determining the range for each critical process parameter expected to be used during routine manufacturing and process control 12.11 关键的工艺参数/属性通常应当在开发阶段或从以往的数据中加以确定，并应当规定工艺可重复性操作所必需的范围。包括：
● 定义原料药生产的关键产品属性；
● 确认可能对原料药关键质量属性有影响的工艺参数；
● 确定在日常生产和工艺控制中会用到的每个关键工艺参数的范围。
12.12 Validation should extend to those operations determined to be critical to the quality and purity of the API. 12.12 验证还应当涉及到那些对原料药质量和纯度至关重要的操作。
12.2 Validation Documentation 12.2 验证文件
12.20 A written validation protocol should be established that specifies how validation of a particular process will be conducted. The protocol should be reviewed and approved by the quality unit(s) and other designated units. 12.20 应当有书面的验证方案，阐明如何进行某个工艺的验证。验证方案应当由质量部门和其他指定的部门审核并批准。
12.21 The validation protocol should specify critical process steps and acceptance criteria as well as the type of validation to be conducted (e.g., retrospective, prospective, concurrent) and the number of process runs. 12.21 验证方案应当明确规定验证的关键工序和认可标准，所要进行的验证类型（回顾性验证、预验证、同步验证）和工序运转的次数。
12.22 A validation report that cross-references the validation protocol should be prepared, summarizing the results obtained, commenting on any deviations observed, and drawing the appropriate conclusions, including recommending changes to correct deficiencies. 12.22 应当拟定一份能交叉引用验证方案的验证报告，概括得到的结果，说明发现的任何偏差，并作出必要的结论，包括为整改而必须做的变更。
12.23 Any variations from the validation protocol should be documented with appropriate justification. 12.23 任何对验证方案的偏离都应当归档备案，并作适当说明。
12.3 Qualification 12.3 确认
12.30 Before initiating process validation activities, appropriate qualification of critical equipment and ancillary systems should be completed. Qualification is usually carried out by conducting the following activities, individually or combined:
● Design Qualification (DQ): documented verification that the proposed design of the facilities, equipment, or systems is suitable for the intended purpose
● Installation Qualification (IQ): documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations and/or user requirements
● Operational Qualification (OQ): documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges
● Performance Qualification (PQ): documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications 12.30 在开始工艺验证活动前，应当完成适当的关键设备和辅助系统的确认。确认一般是通过单独或联合进行以下活动来实行的：
● 设计确认（DQ）：是对提议的设施、设备或系统适用于预期的目的的一种成文的确认；
● 安装确认（IQ）：对安装好的和调整过的设备或系统符合已批准的设计、制造商建议的和/或用户的要求的成文的确认；
● 运行确认（OQ）：对安装好的和调整过的设备或系统能在整个预期的操作范围内按要求运行的成文的确认；
● 性能确认（PQ）：是对设备或其辅助系统在相互连接后，能根据已获准工艺方法和质量标准有效的、重现的进行运转的成文的确认。
12.4 Approaches to Process Validation 12.4 工艺验证的方法
12.40 Process Validation (PV) is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API meeting its predetermined specifications and quality attributes. 12.40 工艺验证（PV）是证明在预定的工艺参数范围内运行的工艺能持续有效地生产出符合预定的质量标准和质量属性的中间体或原料药的证明文件。
12.41 There are three approaches to validation. Prospective validation is the preferred approach, but there are situations where the other approaches can be used. These approaches and their applicability are discussed here. 12.41 验证方法有三种，预验证是首选的方法，但在其它方法可采用的情况下也有例外。这些方法及其适用性见下文。
12.42 Prospective validation should normally be performed for all API processes as defined in 12.1. Prospective validation for an API process should be completed before the commercial distribution of the final drug product manufactured from that API. 12.42 12.1中所述的所有原料药生产工艺一般来说都应当进行预验证。对原料药工艺所作的预验证的结果，必须在用该原料药制成的制剂产品销售前完成。
12.43 Concurrent validation can be conducted when data from replicate production runs are unavailable because only a limited number of API batches have been produced, API batches are produced infrequently, or API batches are produced by a validated process that has been modified. Prior to the completion of concurrent validation, batches can be released and used in final drug product for commercial distribution based on thorough monitoring and testing of the API batches. 12.43 有时由于原料药生产批号有限，原料药批号不是经常生产，或原料药是用验证过的，但已变更的工艺生产的，无法从连续生产中得到数据，可进行同步验证。同步验证完成之前，只要对原料药批号进行了充分的监控和测试，这些批号可以放行并用于最终制剂药的商业销售。
12.44 An exception can be made for retrospective validation well-established processes that have been used without significant changes to API quality due to changes in raw materials, equipment, systems, facilities, or the production process. This validation approach may be used where:
1. Critical quality attributes and critical process parameters have been identified
2. Appropriate in-process acceptance criteria and controls have been established
3. There have not been significant process/product failures attributable to causes other than operator error or equipment failures unrelated to equipment suitability
4. Impurity profiles have been established for the existing API 12.44 某些工艺已确立了很久，而且原料、设备、系统、设施或生产工艺的变化对原料药的质量没有明显的影响，此时就可以例外地进行回顾性验证。这一验证方法适合于下列情况：
1. 关键质量属性和关键工艺参数均已确定；
2. 已确立了合适的过程控制和认可标准；
3. 从来没有因为除了操作人员失误或设备故障这些与设备适应性无关的因素之外的原因而造成值得注意的工艺/产品的不合格；
4. 现有原料药的杂质概况已确定。
12.45 Batches selected for retrospective validation should be representative of all batches produced during the review period, including any batches that failed to meet specifications, and should be sufficient in number to demonstrate process consistency. Retained samples can be tested to obtain data to retrospectively validate the process. 12.45 回顾性验证选用的批号应当能够代表审核时段中的所有批号，包括任何不合格的批号，而且应当有足够的批数来证明工艺的稳定。可用测试留样来获取回顾性工艺验证数据。
12.5 Process Validation Program 12.5 工艺验证的程序
12.50 The number of process runs for validation should depend on the complexity of the process or the magnitude of the process change being considered. For prospective and concurrent validation, three consecutive successful production batches should be used as a guide, but there may be situations where additional process runs are warranted to prove consistency of the process (e.g., complex API processes or API processes with prolonged completion times). For retrospective validation, generally data from 10 to 30 consecutive batches should be examined to assess process consistency, but fewer batches can be examined if justified. 12.50 验证时生产工艺的运行次数，应当由工艺的复杂性或要考虑的工艺变更的大小来决定。作为一个指南，预验证和同步验证应当采用三个连续的、成功的批号，但可能在某些情况下需要更多的批号来保证工艺的一致性（例如，复杂的原料药生产工艺，或原料药工艺耗时很长）。回顾性验证一般应当审查从10到30个连续批号得到的数据来评估工艺的一致性，但是，如果有理由，审查的批数可以少些。
12.51 Critical process parameters should be controlled and monitored during process validation studies. Process parameters unrelated to quality, such as variables controlled to minimize energy consumption or equipment use, need not be included in the process validation. 12.51 在工艺验证研究时应当控制并监测关键的工艺参数。与质量无关的参数，例如为了将能量消耗或所用设备减到最低而控制的变量，无需包括在工艺验证中。
12.52 Process validation should confirm that the impurity profile for each API is within the limits specified. The impurity profile should be comparable to, or better than, historical data and, where applicable, the profile determined during process development or for batches used for pivotal clinical and toxicological studies. 12.52 工艺验证应当确认每一个原料药的杂质概况都在规定的限度内。杂质概况应当与以往的数据相似或更好，如果可能，应当与工艺开发阶段确定的杂质概况，或用于关键的临床和毒理研究的批号的数据相似或更好。
12.6 Periodic Review of Validated Systems 12.6验证系统的定期审核
12.60 Systems and processes should be periodically evaluated to verify that they are still operating in a valid manner. Where no significant changes have been made to the system or process, and a quality review confirms that the system or process is consistently producing material meeting its specifications, there is normally no need for revalidation. 12.60 应当对系统和工艺进行周期性的评价，以确认它们仍然能有效地运作。如果系统或工艺并没有大的变动，而质量回顾证实系统和工艺在稳定地生产着符合其质量标准的物料，通常就不必验证了。
12.7 Cleaning Validation 12.7 清洗验证
12.70 Cleaning procedures should normally be validated. In general, cleaning validation should be directed to situations or process steps where contamination or carryover of materials poses the greatest risk to API quality. For example, in early production it may be unnecessary to validate equipment cleaning procedures where residues are removed by subsequent purification steps. 12.70 通常应当验证清洗程序。一般来说，清洗验证应当针对那些如果受到污染或偶然带入异物就会对原料药的质量带来极大危险的情况或工序。例如，在生产的前期阶段，可能就无需验证设备的清洗程序，那里的残留物会被后面的纯化步骤除去。
12.71 Validation of cleaning procedures should reflect actual equipment usage patterns. If various APIs or intermediates are manufactured in the same equipment and the equipment is cleaned by the same process, a representative intermediate or API can be selected for cleaning validation. This selection should be based on the solubility and difficulty of cleaning and the calculation of residue limits based on potency, toxicity, and stability. 12.71 清洗程序的验证应当反映实际的设备使用情况。如果多个原料药或中间体都在同一设备内生产，而该设备用同一个程序清洗，那么就要选择代表性的中间体或原料药来作清洗验证。应当根据溶解性，清洗难度，以及依据效价、毒性和稳定性计算出来的残留物的限量来作选择。
12.72 The cleaning validation protocol should describe the equipment to be cleaned, procedures, materials, acceptable cleaning levels, parameters to be monitored and controlled, and analytical methods. The protocol should also indicate the type of samples to be obtained and how they are collected and labeled. 12.72 清洗验证方案应当描述要清洗的设备、程序、物料、可接受的清洗程度、要监测和控制的参数、以及分析方法。方案还应当指出要得到的样品的种类，和如何取样及标记。
12.73 Sampling should include swabbing, rinsing, or alternative methods (e.g., direct extraction), as appropriate, to detect both insoluble and soluble residues. The sampling methods used should be capable of quantitatively measuring levels of residues remaining on the equipment surfaces after cleaning. Swab sampling may be impractical when product contact surfaces are not easily accessible due to equipment design and/or process limitations (e.g., inner surfaces of hoses, transfer pipes, reactor tanks with small ports or handling toxic materials, and small intricate equipment such as micronizers and microfluidizers). 12.73 取样应当包括擦拭法、冲洗法或可供选择的方法（如直接萃取），如果合适的话，同时检测不溶性和可溶性的残留物。所用的取样方法应当能定量地检测出清洗之后留在设备表面的残留物质。当与产品接触的表面，由于设备的设计和/或工艺限制（如，软管的内表面，运输管道，反应釜的开口很小或装卸有毒物质，以及一些小的复杂的设备，如微粉粉碎机，流化床式微粉机），很难触及时，擦拭取样就无法实施。
12.74 Validated analytical methods having sensitivity to detect residues or contaminants should be used. The detection limit for each analytical method should be sufficiently sensitive to detect the established acceptable level of the residue or contaminant. The method’s attainable recovery level should be established. Residue limits should be practical, achievable, verifiable, and based on the most deleterious residue. Limits can be established based on the minimum known pharmacological, toxicological, or physiological activity of the API or its most deleterious component. 12.74 应当采用验证过的、具有检测残留物或污染物的灵敏度的分析方法。每一个分析方法的检测限度必须足够灵敏，来检测到残留物或污染物的规定的可接受水平。应当规定方法的可达到的回收率。残留物的限度切实可行的，可检测的，并由最有害的残留物来确定。可以根据原料药或其最有害的组分的已知最小药理、毒理或生理活性浓度来制定限度。
12.75 Equipment cleaning/sanitation studies should address microbiological and endotoxin contamination for those processes where there is a need to reduce total microbiological count or endotoxins in the API, or other processes where such contamination could be of concern (e.g., non-sterile APIs used to manufacture sterile products). 12.75 对于需要降低原料药中的总微生物数或内毒素的工艺，或担心此类污染的其它工艺（如，用于生产无菌产品的非无菌原料药），设备清洗/消毒的研究应当对付微生物和内毒素污染。
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