Q7a
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.
6.6 Laboratory Control Records
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
6.61 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
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 实验室控制记录
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 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；
25
Q7a
● Out-of-specification (OOS) investigations
6.7 Batch Production Record Review
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.
6.71 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).
6.72 All deviation, investigation, and OOS reports should be reviewed as part of the batch record review before the batch is released.
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.
7. MATERIALS MANAGEMENT 7.1 General Controls
7.10 There should be written procedures describing the receipt, identification, quarantine, storage, handling, sampling, testing, and approval or rejection of materials.
7.11 Manufacturers of intermediates and/or APIs should have a system for evaluating the suppliers of critical materials.
7.12 Materials should be purchased against an agreed specification, from a supplier, or suppliers, approved by the quality unit(s).
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
● 原料药的所有稳定性测试； ● 不合格的调查。
6.7批生产记录审核
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 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 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 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. 物料管理 7.1 控制通则
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 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 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 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。
26
Q7a
the intermediate and/or API manufacturer.
7.14 Changing the source of supply of critical raw materials should be treated according to Section 13, Change Control.
7.2 Receipt and Quarantine
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.
7.21 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.
7.22 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
7.23 Large storage containers and their attendant manifolds, filling, and discharge lines should be appropriately identified.
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.
7.3 Sampling and Testing of Incoming Production Materials
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
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接收和待验
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 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 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 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 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 进厂物料的取样与测试
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
27
Q7a
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.
7.31 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.
7.32 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.
7.33 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.
7.34 Sampling should be conducted at defined locations and by procedures designed to prevent contamination of the material sampled and contamination of other materials.
7.35 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.
替代其他项目的测试。
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 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 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 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 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。
28