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7.40 Materials should be handled and stored in a manner to prevent degradation, contamination, and cross-contamination.
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.
7.42 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.
7.43 Certain materials in suitable containers can be stored outdoors, provided identifying labels remain legible and containers are appropriately cleaned before opening and use.
7.44 Rejected materials should be identified and controlled under a quarantine system designed to prevent their unauthorized use in manufacturing.
7.5 Re-evaluation
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).
8. PRODUCTION AND IN-PROCESS CONTROLS
8.1 Production Operations
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.
8.11 If a material is subdivided for later use in production operations, the container receiving the material should be suitable and should be so
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 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 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 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 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重新评估
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. 生产和过程控制
8.1 生产操作
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 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：
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identified that the following information is available:
● 物料的名称和/或货号； ● Material name and/or item code
● 接收号或控制号； ● Receiving or control number
● Weight or measure of material in the new ● 新容器中物料的重量或计量；
container
● 如有必要，标明复验期。 ● Re-evaluation or retest date if appropriate
8.12 Critical weighing, measuring, or 8.12 关键的称重、测量或分装操作应当有人subdividing operations should be witnessed or 作证或接受相应的控制。使用前，生产人员subjected to an equivalent control. Prior to use, 应当确认该物料是要生产的中间体或原料药production personnel should verify that the 的批记录中指定的。 materials are those specified in the batch record for the intended intermediate or API.
8.13 Other critical activities should be 8.13 其它关键活动应当有人作证或接受相应witnessed or subjected to an equivalent control. 的控制。
8.14 Actual yields should be compared with 8.14 在生产过程中的指定步骤，实际收率应expected yields at designated steps in the 当与预计的收率作比较。具有合适范围的预production process. Expected yields with 计收率应当根据以前的实验室、中试规模或appropriate ranges should be established based 生产的数据来确定。应当调查与关键工艺步on previous laboratory, pilot scale, or 骤有关的收率偏差，以确定其对相关批号最manufacturing data. Deviations in yield 终质量的影响或潜在影响。 associated with critical process steps should be investigated to determine their impact or potential impact on the resulting quality of affected batches.
8.15 Any deviation should be documented and 8.15 任何偏差都应当记录，并作解释。任何explained. Any critical deviation should be 关键的偏差应当作调查。 investigated.
8.16 The processing status of major units of 8.16 应当标明主要设备的生产状态，可以标equipment should be indicated either on the 在每个设备上，或者用文件、计算机控制系individual units of equipment or by appropriate 统或其它替代的方法。 documentation, computer control systems, or alternative means.
8.17 Materials to be reprocessed or reworked 8.17 对需要进行返工或重新加工的物料应当should be appropriately controlled to prevent 适当地加以控制，防止未经许可就使用。 unauthorized use. 8.2 Time Limits 8.2 时限
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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.
8.21 Intermediates held for further processing should be stored under appropriate conditions to ensure their suitability for use.
8.3 In-process Sampling and Controls
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.
8.31 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).
8.32 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).
8.33 In-process controls can be performed by qualified production department personnel and
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 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 工序间的取样和控制
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 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 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 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
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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.
8.34 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.
8.35 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.
8.36 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.
8.4 Blending Batches of Intermediates or APIs
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.
8.41 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.
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 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 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 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 中间体或原料药的混批
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 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。
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8.42 Acceptable blending operations include, 8.42 可接受的混合操作包括但不限于： but are not limited to:
● Blending of small batches to increase batch ● 将小批混合，增大批量；
size
● Blending of tailings (i.e., relatively small ● 将多批同一中间体或原料药的尾料（例
quantities of isolated material) from 如，分离出的相对较少的量）混合成为一batches of the same intermediate or API to 个批号。 form a single batch
8.43 Blending processes should be adequately 8.43 混合过程应当充分控制并记录，混合后controlled and documented, and the blended 的批号应当根据情况进行测试，以确认是否batch should be tested for conformance to 达到质量标准。 established specifications, where appropriate.
8.44 The batch record of the blending process 8.44 混合过程的批记录应当允许追溯到参与should allow traceability back to the individual 混合的每个单独批号。 batches that make up the blend.
8.45 Where physical attributes of the API are 8.45 如果原料药的物理性质至关重要（例如，critical (e.g., APIs intended for use in solid oral 用于固体口服制剂或混悬剂的原料药），混合dosage forms or suspensions), blending 工艺应当验证，以显示混合后批号的均匀性。operations should be validated to show 验证应当包括测试可能受混合过程影响的关homogeneity of the combined batch. Validation 键属性（例如，粒度分布，堆密度和振实密should include testing of critical attributes (e.g., 度）。 particle size distribution, bulk density, and tap density) that may be affected by the blending process.
8.46 If the blending could adversely affect 8.46 如果混合会对稳定性有不良影响，应当stability, stability testing of the final blended 对最终混合批号进行稳定性测试。 batches should be performed.
8.47 The expiry or retest date of the blended 8.47 混合批号的有效期或复验期应当以混合batch should be based on the manufacturing 中生产日期最早的尾料或批次的批号为基date of the oldest tailings or batch in the blend. 准。 8.5 Contamination Control 8.5 污染控制
8.50 Residual materials can be carried over into 8.50 在得到充分控制的前提下，上一批号的successive batches of the same intermediate or 同一中间体或原料药的剩余物可以带入下几API if there is adequate control. Examples 个连续批号。例如，黏附在微粉机壁上的残include residue adhering to the wall of a 留，离心出料后残留在离心机筒体内的潮湿micronizer, residual layer of damp crystals 的结晶，将物料转至下一步工序时无法从反remaining in a centrifuge bowl after discharge, 应器中彻底放尽的物料。此类带入不应当导
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