USP36 1117 优良微生物检测规范（中英文2/2）

巴西木

SAMPLE HANDLING 样品制备

Viable microorganisms in most microbiology samples, particularly water, environmental monitoring and bioburden samples, are sensitive to handling and storage conditions. Critical parameters in these conditions include product (or sample) composition, container composition, time of storage, and temperature of storage. Therefore, it is important to minimize the amount of time between the sampling event and the initiation of testing and to control, as much as possible, the conditions of storage. If the sample is to be transported to a distant location for testing, then the conditions of transport (time, temperature, etc.) should be qualified as suitable for that test and sample. Guidance for water testing in this regard can be found in Water for Pharmaceutical Purposes 1231 . Product mixing before sampling may need to be evaluated and applied in order to ensure microbial dispersement and representation in the sample aliquot.

大多数微生物样品中的活菌，尤其是水样、环境监控样品和生物负载样品，对处置过程和存贮条件非常敏感。这些环境下的关键参数包括产品（或样品）成分、容器成份、存贮时长、存贮温度。因此，尽量缩短取样和检验开始的时间间隔非常重要，以及尽可能控制存贮环境。如果样品需要送到一个较远的检测场所，则传送条件（时间、温度等）应针对所做的检测和样品进行确认以保证其合适。有关水检测的指南参见1231制药用水。在取样前即进行混合的产品可能需要进行评估，以保证微生物水平及样品代表性。

All microbiological samples should be taken using aseptic techniques, including those taken in support of nonsterile products. If possible, all microbiological samples should be taken under full aseptic conditions in specialized sampling areas. The areas should be as close to the point of use as possible to minimize contamination during transit.

所有用于微生物检测的样品均应在无菌环境下取样，包括用于非无菌制剂的样品。如有可能，所有微生物检测用样品应在特定的无菌条件的取样区域取样，该区域应与使用时的环境尽可能接近，以最大程度降低转移过程中的污染。

Samples submitted to the microbiology laboratory should be accompanied by documentation detailing source of the sample, date the sample was taken, date of sample submission, person or department responsible for the submission, and any potentially hazardous materials associated with the sample. The testing department should acknowledge receipt of the sample and reconcile the identity and number of samples as part of this sample documentation.

样品传递至微生物化验室时应附有详细的记录，包括样品来源、取样日期、样品传递日期、传递人员或部门、样品可能会含有的危险物质。检验部分应告知样品收到，并核对编号和样品数量，在取样记录中注明。

MICROBIOLOGICAL MEDIA INCUBATION TIMES 微生物培养基培养时间

Incubation times for microbiological tests of less than 3 days' duration should be expressed in hours: e.g., “Incubate at 30 to 35 for 18 to 72 hours”. Tests longer than 72 hours' duration should be expressed in days: e.g., “Incubate at 30 to 35 for 3 to 5 days”. For incubation times expressed in hours, incubate for the minimum specified time, and exercise good microbiological judgment when exceeding the incubation time. For incubation times expressed in days, incubations started in the morning or afternoon should generally be concluded at that same time of day.

微生物测试的培养时间如果少于3天，则应表述为小时，例如“在30-35℃培养18-72小时”。如果大于72小时，则应表述为天数，例如“在30-35℃培养3-5天”。如果培养时间以小时计，则培养时间应为指定的最短时间，如果超出指定的培养时间，则需要应用好的微生物判断。如果培养时间以天计，则上午或下午开始进行培养一般会在结束天的同一时间进行判定。

TRAINING OF PERSONNEL 人员培训

Each person engaged in each phase of pharmaceutical manufacture should have the education, training, and experience to do his or her job. The demands of microbiological testing require that the core educational background of the staff, supervisors, and managers be in microbiology or a closely related biological science. They should be assigned responsibilities in keeping with their level of skill and experience.

参与药品生产各阶段活动的所有人员均需要进行教育、培训，具备其所操作岗位的经验。微生物检测岗位要求操作人员、主管和经理的基本教育背景为微生物学或相关生物学科。公司应根据人员的技能水平和经验赋予不同的责任。

A coherent system of standard operating procedures (SOPs) is necessary to run the microbiology laboratory. These procedures serve two purposes in a training program. Firstly, these SOPs describe the methodology that the microbiologist will follow to obtain accurate and reproducible results, and so serve as the basis for training. Secondly, by tracking the procedures in which a particular microbiologist has demonstrated proficiency, the procedure number or title also serves to identify what training the microbiologist has received specific to his or her job function.

要使微生物室正常运行，需要有一套条理分明的标准操作规程（SOP）。这些程序对于培训来说有两个目的，一是这些SOP描述了微生物化验员需要遵守以获得准确和可重复的结果的方法，从而作为培训的基础教材，二是在SOP中由指定的微生物化验员进行了专业描述，该SOP的编号和题目可以用以识别微生物化验员接受了其岗位所对应的培训。

Training curricula should be established for each laboratory staff member specific to his or her job function.

对各化验室人员，应根据其岗位要求制订相应的培训课程。

He or she should not independently conduct a microbial test until qualified to run the test. Training records should be current, documenting the microbiologist's training in the current revision to the particular SOP.

化验室人员在未获得资格前，不得独立进行微生物测试。培训记录应保持更新，记录微生物化验员根据特定SOP现行版本所进行的培训。

Periodic performance assessment is a wise investment in data quality. This performance testing should provide evidence of competency in core activities of the microbiology laboratory such as hygiene, plating, aseptic technique, documentation, and others as suggested by the microbiologist's job function.

对化验员进行周期性的绩效评估是对数据品质的明智投资。这种行为测试应提供微生物核心活动合格的证据，如卫生、铺碟、无菌操作、记录和其它微生物化验员工作内容的活动。

Microbiologists with supervisory or managerial responsibilities should have appropriate education and inhouse training in supervisory skills, laboratory safety, scheduling, budgeting, investigational skills, technical report writing, relevant SOPs, and other critical aspects of the company's processes as suggested in their role of directing a laboratory function.

微生物室具有监督或管理职责的人员应具有适当的教育背景，以及公司内部培训，内容包括监管技巧、化验室安全、制订计划、制订预算、调查技巧、技术报告书写、相关SOP、公司程序所要求其岗位应具体的领导化验室的职责的其它关键方面。

Competency may be demonstrated by specific course work, relevant experience, and routinely engaging in relevant continuing education. Achieving certification through an accredited body is also a desirable credential. Further, it is expected that laboratory supervisors and managers have a demonstrated level of competence in microbiology at least as high as those they supervise. Expertise in microbiology can be achieved by a variety of routes in addition to academic course work and accreditation. Each company is expected to evaluate the credentials of those responsible for designing, implementing, and operating the microbiology program. Companies can thus ensure that those responsible for the program understand the basic principles of microbiology, can interpret guidelines and regulations based on good science, and have access to individuals with theoretical and practical knowledge in microbiology to provide assistance in areas in which the persons responsible for the program may not have adequate knowledge and understanding. It should be noted that microbiology is a scientifically based discipline that deals with biological principles substantially different from those of analytical chemistry and engineering disciplines.

人员是否合格可以通过特定工作、相关经验和日常从事相关持续教育进行证明。获得相关机构的证书也是一种理想的方法。另外，最好化验室主管和经理能具备其所监管的微生物工作的至少同样水平的能力。除通过专业课程和专业机构证书外，也可以通过不同的方法达到微生物专业水平。公司应评估负责微生物程序设计、实施和操作的负责人员的证书，从而保证这些人员具备基本的微生物原理，可以对指南和法规基于科学理论进行解释，并知晓哪些人具备理论和实践微生物知识，能在负责某程序的人不具备充分知识和理解时提供相关的帮助。需要注意的是，微生物学是一门科学严谨的学问，是与生物原则相关的学科，根本区别于分析化学和工程学原理。

Many times it is difficult for individuals without specific microbiological training to make the transition.

一个人如果没有特定的微生物培训知识，要进行知识传递是非常困难的。

LABORATORY RESOURCES 化验室资源

The laboratory management is responsible for ensuring that the laboratory has sufficient resources to meet the existing testing requirements. This requires some proficiency in budget management and in determining appropriate measures of laboratory performance. A measure of laboratory performance is the number of investigations performed on tests conducted by the laboratory, but this measure alone is not sufficient. In addition to tracking investigations, the period of time between sample submission and initiation of testing should be tracked, as well as the period of time between end of test and report release (or test closure). Significant delays in these measures are also indications of an under-resourced laboratory staff.

实验室管理人员应保证实验室具有充足的资源，以满足现有的检测要求。要做到这点，需要有充足的预算以及对化验室表现做出适当的评估。化验室表现的评估标准之一是化验室所做检测的调查数量，但仅采用该标准是不够的。除了追踪调查之外，还应追踪样品传送间隔和检测开始时间，以及检测结束到出具报告（或检测关闭）的时间间隔。这些行为的延迟也说明化验室人员未满足资源要求。

The laboratory management should have sufficient budget to meet testing requirements. Particular measures of budgetary requirements will be specific to the given laboratory, but budgetary considerations related directly to the need of the laboratory for sufficient resources must be addressed to ensure reliable testing results.

化验室管理应具备充足的预算，以满足检测的要求，预算应细化针对各特定的化验室，与化验室资源是否充分直接相关的预算要求则必须进行说明，以保证获得可靠的检测结果。

DOCUMENTATION 文件记录

Documentation should be sufficient to demonstrate that the testing was performed in a laboratory and by methods that were under control. This includes, but is not limited to, documentation of the following:

应有充分文件证明微生物检测是根据受控的方法、在受控的化验室完成的。文件包括，但不限于以下

—       Microbiologist training and verification of proficiency

—       微生物检验人员培训和熟练度确认

—       Equipment validation, calibration, and maintenance

—       仪器验证、校正和维护

—       Equipment performance during test (e.g., 24-hour/7-day chart recorders)

—       测试期间仪器性能（例如24小时/7天连续记录）

—       Media preparation, sterility checks, and growth-promotion and selectivity capabilities

—       培养基制备、灭菌检查和促生长试验及选择性检查

—       Media inventory and control testing

—       培养基库存和控制检测

—       Critical aspects of test conducted as specified by a procedure

—       根据程序进行的检测的关键部分

—       Data and calculations verification

—       数据和计算复核

—       Reports reviewed by QAU or a qualified responsible manager

—       报告由QA部门或负责人审核

—       Investigation of data deviations (when required)

—       对偏差数据进行调查（如果必要）

MAINTENANCE OF LABORATORY RECORDS 化验室记录保存

Proper recording of data and studies is critical to the success of the microbiology laboratory. The over-riding principle is that the test should be performed as written in the SOP, the SOP should be written to reflect how the test is actually performed, and the laboratory notebook should provide a record of all critical details needed to reconstruct the details of the testing and confirm the integrity of the data. At a minimum, the laboratory write-up should include the following:

对数据和研究进行适当的记录是微生物化验室成功的关键。首要原则是必须根据书面SOP要求进行检测，SOP必须是书面的，反映真实操作。化验室记录本应记录所有关键细节，以便重现检测操作，确认数据的完整性。化验室记录至少应包括以下内容

—       Date

—       日期

—       Material tested

—       检测样品名

—       Microbiologist's name

—       微生物名称

—       Procedure number

—       程序编号

—       Document test results

—       记录检测结果

—       Deviations (if any)

—       偏差（如有）

—       Documented parameters (equipment used, microbial stock cultures used, media lots used)

—       记录参数（所用仪器、所用微生物库存培养、所用培养基批号）

—       Management/Second review signature

—       管理者/复核签字

Every critical piece of equipment should be noted in the write-up, and all should be on a calibration schedule documented by SOP and maintenance records. Where appropriate, logbooks or forms should be available and supportive of the laboratory notebook records. Equipment temperatures (water baths, incubators, autoclaves) should be recorded and traceable.

所有关键设备均应记录，且应具有SOP所规定的校正计划和维护记录。适当时，设备日志或记录表格应在现场，并与化验室记录本内容一致。设备温度（水浴、培养箱、灭菌器）应有记录并可追踪。

The governing SOP and revision should be clearly noted in the write-up. Changes in the data should be crossed off with a single line and initialed. Original data should not be erased or covered over.

所执行的SOP及其版本应记录清楚。数据修正应对原数据划单删除线，在旁边另书写正确认数据。原始数据应保持不被擦除或覆盖。

Test results should include the original plate counts, allowing a reviewer to recreate the calculations used to derive the final test results. Methods for data analysis should be detailed in cited SOPs. If charts or graphs are incorporated into laboratory notebooks, they should be secured with clear tape and should not be obstructing any data on the page. The chart or graph should be signed by the person adding the document, with the signature overlapping the chart and the notebook page. Lab notebooks should include page numbers, a table of contents for reference, and an intact timeline of use.

检测结果应包括原始碟计数结果，使审核人员可以重新计算结果。数据分析方法应在SOP中详细说明。如果检验记录中需要引入图表，这些图表应采用透明胶带保护，且不能遮挡该记录页上的任何其它数据。将图表附入记录的人员应在图表上签字，签字应在图表和记录本之间骑缝。化验室记录本应编有页码，索引表，使用起止时间。

All laboratory records should be archived and protected against catastrophic loss. A formal record retention and retrieval program should be in place.

所有化验室数据应归档，并防止不可恢复的损坏。应有正式的记录保管和检索程序。

INTERPRETATION OF ASSAY RESULTS 含量结果解释

Analytical microbiological assay results can be difficult to interpret for several important reasons: (1) Microorganisms are ubiquitous in nature, and common environmental contaminants—particularly organisms associated with humans—predominate in many types of microbiological analysis; (2) the analyst has the potential to introduce contaminating organisms during sample handling or processing in the laboratory; (3) microorganisms may not be homogeneously distributed within a sample or an environment; and (4) microbiological assays are subject to considerable variability of outcome. Therefore, apparent differences from an expected outcome may not be significant.

微生物含量结果可能很难进行解释，重要原因如下：

（1）     微生物在自然界中无所不在，常见环境污染---特别是由人类携带的微生物---在许多微生物分析中占主导地位

（2）     分析员可能会在样品在化验室内操作或处理过程中带入污染菌

（3）     微生物在样品或环境中可能并不均匀存在

（4）     微生物含量会产生很大的结果差异

因此，与期望结果产生差异可能比较显著。

Because of these characteristics of microbiological analysis, laboratory studies should be conducted with the utmost care to avoid exogenous contamination as previously discussed in this chapter. Equally important, results must be interpreted from a broad microbiological perspective, considering not only the nature of the putative contaminant, but the likelihood of that organism(s) surviving in the pharmaceutical ingredient, excipient, or environment under test. In addition, the growth characteristics of the microorganism should be considered (especially in questions of the growth of filamentous fungi in liquid media).

由于微生物分析的这些特性，化验室在进行研究时需要非常注意以避免本章中已讨论的外来污染。同样重要的是，应从广义的微生物角度对结果进行解释，不仅要考虑假定污染的特性，也要考虑微生物在药用成份、辅料或测试环境下存活的可能性，还要考虑微生物生长特性（尤其是液体培养基中丝状真菌生长的问题）。

When results are observed that do not conform to a compendial monograph or other established acceptance criteria, an investigation into the microbial data deviation (MDD) is required. There are generally two distinct reasons for the observation of microbial contamination that does not comply with a target or requirement: There may be either a laboratory error or laboratory environmental conditions that produced an invalid result, or the product contains a level of contamination or specific types of contaminants outside established levels or limits. In either case, laboratory management and, in most cases, the Quality Unit should be notified immediately.

如果所得到的结果与药典各论或其它已有可接受标准不符合，则需要对微生物数据偏差（MDD）进行调查。一般来说会有两个原因导致微生物污染使得结果不符合要求的结果，第一个可能是化验操作错误或化验室环境条件导致无效结果，第二个可能是产品受到一定程度污染、或特定污染超出了既定水平或限度。不管是何种情况，应立即通知化验室管理人员和，在多数情况下，质量部门。

A full and comprehensive evaluation of the laboratory situation surrounding the result should be undertaken.

应对结果相关的所有化验室条件进行综合全面评估。

All microbiological conditions or factors that could bring about the observed condition should be fully considered, including the magnitude of the excursion compared to established limits or levels. In addition, an estimate of the variability of the assay may be required in order to determine whether the finding is significant.

所有可能会导致所观察到的条件的微生物条件或因素均需要进行充分考虑，包括与已有限度或水平的重大偏离。另外，可能需要对含量变动性进行评估以决定所发现的问题是否重大。

The laboratory environment, the protective conditions in place for sampling, historical findings concerning the material under test, and the nature of the material, particularly with regard to microbial survival or proliferation in contact with the material, should be considered in the investigation. In addition, interviews with the laboratory analyst(s) may provide information regarding the actual conduct of the assay that can be valuable in determining the reliability of the result and in determining an appropriate course of action. If laboratory operations are identified as the cause of the nonconforming test outcome, then a corrective action plan should be developed to address the problem(s). Following the approval and implementation of the corrective action plan, the situation should be carefully monitored and the adequacy of the corrective action determined.

化验室环境、取样时防护条件、与受检物料相关的历史信息、物料属性、尤其是与物料接触后微生物存活或增生情况，均应在调查时进行考虑。另外，与化验员进行面谈可能会提供与实际操作相关的信息，这些信息在确认结果可靠性和操作适当性方面会很有价值。如果化验室操作经确认是检测结果不符合要求的原因，则需要针对该问题制订纠正措施。在纠正措施及实施计划批准后和实施后，应对改善后的条件进行监控，确认纠正措施的充分性。

If assay results are invalidated on the basis of the discovery of an attributable error, this action must be documented. Laboratories also should have approved procedures for confirmatory testing (retesting), and if necessary, resampling where specific regulatory or compendial guidance does not govern the conduct of an assay investigation.

如果含量结果由于无归属的错误而无效，由该措施应进行记录。化验室应批准进行确认检测（复测），必要时，如果相关法规或药典指南未要求实施含量异常调查，进行重新取样。

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(GCM2010) General Chapters - Microbiology

USP36 1117 优良微生物检测规范（中英文1/2）
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-------翻译人：Julia

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