FDA-微生物实验室检查指南（中英文对照版）

GUIDE TO INSPECTIONS OF MICROBIOLOGICAL PHARMACEUTICAL QUALITY CONTROL LABORATORIES
微生物实验室检查指南

Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does not confer any rights, privileges, benefits, or immunities for or on any person(s). 
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I. INTRODUCTION介绍
The Guide to the Inspection of Pharmaceutical Quality Control Laboratories provided very limited guidance on the matter of inspection of microbiological laboratories. While that guide addresses many of the issues associated with the chemical aspect of laboratory analysis of pharmaceuticals, this document will serve as a guide to the inspection of the microbiology analytical process. As with any laboratory inspection, it is recommended that an analyst (microbiologist) who is familiar with the tests being inspected participate in these inspections.
质检化验室的检查指南重点强调了有关化学分析方面的内容，对于微生物检查的内容涉及比较少，本文将作为化验室检查中对微生物检查方面的指南。对于任何一次质检室的检查，我们都建议需要有熟悉这方面知识的分析学家或者微生物学家参与检查。

II. MICROBIOLOGICAL TESTING OF NON-STERILE PRODUCTS非无菌产品的微生物测试
For a variety of reasons, we have seen a number of problems associated with the microbiological contamination of topical drug products, nasal solutions and inhalation products. The USP Microbiological Attributes Chapter <1111> provides little specific guidance other than "The significance of microorganisms in non-sterile pharmaceutical products should be evaluated in terms of the use of the product, the nature of the product, and the potential hazard to the user." The USP recommends that certain categories be routinely tested for total counts and specified indicator microbial contaminants. For example natural plant, animal and some mineral products for Salmonella, oral liquids for E. Coli, topicals for P. aeruginosa and S. Aureus, and articles intended for rectal, urethral, or vaginal administration for yeasts and molds. A number of specific monographs also include definitive microbial limits.
由于种种理由，我们发现一些外用制剂、滴鼻剂和吸入剂会产生微生物污染的问题。但USP中有关微生物检测的章节<1111>对此方面只提到了“对于非无菌药品的微生物特性，应根据产品用途、产品特性以及对使用者产生的潜在危害进行评价”。USP建议对某些种类的药品应进行微生物污染总数及微生物鉴定方面的检测。例如，对植物药、动物药和某些矿物药应进行沙门氏菌的检测，对口服液应进行大肠杆菌的检测，对外用制剂应进行绿脓杆菌和金黄色葡萄球菌的检测，对供直肠、尿道或阴道用的制剂应进行酵母菌和霉菌的检测。在药典的一些各论中也包括了特定的微生物限度要求。
As a general guide for acceptable levels and types of microbiological contamination in products, Dr. Dunnigan of the Bureau of Medicine of the FDA commented on the health hazard. In 1970, he said that topical preparations contaminated with gram negative organisms are a probable moderate to serious health hazard. Through the literature and through our investigations, it has been shown that a variety of infections have been traced to the gram negative contamination of topical products. The classical example being the Pseudomonas cepacia contamination of Povidone Iodine products reported by a hospital in Massachusetts several years ago.
作为药品微生物污染可接受水平和类型的总指南，FDA药物局的Dunnigan博士对微生物所产生的健康危害作了评论。在1970年，他指出使用被革兰氏阴性菌污染的外用制剂会产生中度到重度的健康为害。通过文献的报道及我们的调查发现，多种感染都与外用制剂的革兰氏阴性菌污染有关。最典型的例子就是几年前在麻萨诸塞州的一家医院发生的洋葱假单胞菌污染聚维酮碘事件。
Therefore, each company is expected to develop microbial specifications for their non-sterile products. Likewise, the USP Microbial Limits Chapter <61> provides methodology for selected indicator organisms, but not all objectionable organisms. For example, it is widely recognized that Pseudomonas cepacia is objectionable if found in a topical product or nasal solution in high numbers; yet, there are no test methods provided in the USP that will enable the identification of the presence of this microorganism.
因此，每家公司都应该为他们的非无菌药品制定微生物限度标准。USP微生物限度章节<61>也提供了检测一些微生物的方法，但并不包括所有的致病菌。例如，在外用制剂或者滴鼻剂中如存在大量的洋葱假单胞菌会对人体产生危害，但是，在USP中却未能提供鉴别该微生物的方法。
A relevant example of this problem is the recall of Metaproterenol Sulfate Inhalation Solution. The USP XXII monograph requires no microbial testing for this product. The agency classified this as a Class I recall because the product was contaminated with Pseudomonas gladioli/cepacia. The health hazard evaluation commented that the risk of pulmonary infection is especially serious and potentially life-threatening to patients with chronic obstructive airway disease, cystic fibrosis, and immuno-compromised patients. Additionally, these organisms would not have been identified by testing procedures delineated in the general Microbial Limits section of the Compendia.
有关这个问题的相应例子还有对间羟异丙肾上腺素吸入剂的召回事件。USPXXII专论中规定对这种产品不需要进行微生物检测。但FDA将被唐菖蒲假单胞菌污染的间羟异丙肾上腺素吸入剂作为I类召回。不良反应评估指出这些污染菌对肺部感染的风险非常大，并且对患有慢性阻塞性呼吸道疾病、囊肿性纤维化和免疫功能低下的病人具有潜在的生命威胁。然而，药典中有关微生物限度检测章节中介绍的方法并不能检测出这种细菌。
The USP currently provides for retests in the Microbial Limits section <61> however there is a current proposal to remove the retest provision. As with any other test, the results of initial test should be reviewed and investigated. Microbiological contamination is not evenly dispersed throughout a lot or sample of product and finding a contaminant in one sample and not in another does not discount the findings of the initial sample results. Retest results should be reviewed and evaluated, and particular emphasis should be placed on the logic and rationale for conducting the retest.
现行的USP微生物限度章节<61>规定微生物检测要进行复测，但是现在也有人建议应取消这一规定。与其他检测一样，对初测的结果应进行回顾和检查。微生物污染不会均匀的分布在一批产品或取样的样品中，在一个样品发现微生物，而在另一个样品中没有发现微生物并不会对最初的检测结果产生影响。复测的结果应进行回顾和评价，但是更应该强调复测方法的基本原理和合理性。
In order to isolate specific microbial contaminants, FDA laboratories, as well as many in the industry, employ some type of enrichment media containing inactivators, such as Tween or lecithin. This is essential to inactivate preservatives usually present in these types of product and provides a better medium for damaged or slow growing cells. Other growth parameters include a lower temperature and longer incubation time (at least 5 days) that provide a better survival condition for damaged or slow-growing cells.
为了分离出产品中的微生物，FDA实验室与许多药品生产企业的实验室一样，采用一些含有抑制剂如吐温或卵磷脂的培养基。这种培养基能使产品中的防腐剂失效，并能为已受损的或生长缓慢的微生物细胞提供更好的生长环境。其它一些生长参数如较低的培养温度和较长的培养时间（至少5天）也能为受损细胞和生长缓慢的细胞提供更好的生长环境。
For example, FDA laboratories use the test procedures for cosmetics in the Bacteriological Analytical Manual (BAM), 6th Edition, to identify contamination in non-sterile drug products. This testing includes an enrichment of a sample in modified letheen broth. After incubation, further identification is carried out on Blood Agar Plates and MacConkey Agar Plates. Isolated colonies are then identified. This procedure allows FDA microbiologists to optimize the recovery of all potential pathogens and to quantitate and speciate all recovered organisms. Another important aspect of procedures used by FDA analysts is to determine growth promotion characteristics for all of the media used.
例如，FDA实验室采用《细菌分析指南》第6章中的化妆品检测方法来鉴别污染非无菌药品的微生物。这种方法包括在改良的letheen肉汤中进行微生物的聚集。经培养后，在血琼脂和麦康凯琼脂培养皿中作进一步的鉴别。这个鉴别方法要求FDA的微生物学家对所有潜在的致病菌的复苏进行最优化处理，并对复苏后的微生物进行计数和分类。这种方法的另外一个重要的作用就是用来确定在所有使用的培养基中微生物的生长特性。
The selection of the appropriate neutralizing agents are largely dependent upon the preservative and formulation of the product under evaluation. If there is growth in the enrichment broth, transfer to more selective agar media or suitable enrichment agar may be necessary for subsequent identification.
选择合适的中和剂很大程度上决定于产品的防腐剂及处方组成。如果在增菌培养肉汤中有菌落生长，那么应将该菌落转移到更具有选择性的琼脂培养基或者合适的增菌琼脂中继续培养，这对于接下来的微生物鉴别是很有必要的。
Microbiological testing may include an identification of colonies found during the Total Aerobic Plate Count test. Again, the identification should not merely be limited to the USP indicator organisms.
微生物检测应包括对细菌总数测试中发现的菌落进行鉴别，而且，这种鉴别应不仅仅局限于USP规定的鉴别方法。
The importance of identifying all isolates from either or both Total Plate Count testing and enrichment testing will depend upon the product and its intended use. Obviously, if an oral solid dosage form such as a tablet is tested, it may be acceptable to identify isolates when testing shows high levels. However, for other products such as topicals, inhalants or nasal solutions where there is a major concern for microbiological contamination, isolates from plate counts, as well as enrichment testing, should be identified.
对细菌总数测试和增菌测试中发现的菌落数进行鉴别的重要性取决于产品本身及预期用途。如果在检测口服固体制剂如片剂时，可以允许在微生物污染水平较高时才进行微生物的鉴别。但是，对于其它制剂，如外用制剂，吸入剂或者滴鼻剂，一旦在细菌总数测试和增菌测试中发现有菌落存在，就应该立即进行微生物鉴别。

III. FACILITIES, EQUIPMENT, AND  MEDIA设施、设备和培养基
Begin the inspection with a review of analyses being conducted and inspect the plates and tubes of media being incubated (caution should be exercised not to inadvertently contaminate plates or tubes of media on test). Be particularly alert for retests that have not been documented and “special projects” in which investigations of contamination problems have been identified. This can be evaluated by reviewing the ongoing analyses (product or environmental) for positive test results. Request to review the previous day’s plates and media, if available and compare your observations to the recorded entries in the logs. Inspect the autoclaves used for the sterilization of media. Autoclaves may lack the ability to displace steam with sterile filtered air. For sealed bottles of media, this would not present a problem. However, for non-sealed bottles or flasks of media, non-sterile air has led to the contamination of media. In addition, autoclaving less than the required time will also allow media associated contaminants to grow and cause a false positive result. These problems may be more prevalent in laboratories with a heavy workload.
检查开始前应对分析方法进行回顾，并检查用来培养微生物的培养皿和试管（对防止培养皿和试管被微生物污染应有警示说明）。要特别值得注意的是，复测项目是否形成文件，对微生物污染调查中的特殊项目是否确定。这些内容在回顾阳性结果的分析过程（产品因素或环境因素）都应该进行评价。应该要求对前一天的培养皿和培养基进行观察，并与之前的记录进行比较。对用于灭菌的压力蒸汽灭菌锅进行检查。压力蒸汽灭菌锅不能将蒸汽替代为无菌过滤空气，因此，对于密封的瓶装培养基来说，这是没有问题的。但是对于非密封性的培养器皿来说，非无菌空气就有可能会污染培养基。另外，灭菌时间少于规定时间也会使培养介质灭菌不彻底，引起检测结果的假阳性。这些问题在工作量大的实验室中是普遍存在的。
Check the temperature of the autoclave since overheating can denature and even char necessary nutrients. This allows for a less than optimal recovery of already stressed microorganisms. The obvious problem with potential false positives is the inability to differentiate between inadvertent medium contamination and true contamination directly associated with the sample tested.
过热会引起培养基中的营养物质变性或烧焦，因此应对压力蒸汽灭菌器的温度进行检查。温度应低于上述强调的微生物的最佳复原温度。对于假阳性结果的出现，最明显的问题就是不能区分这个结果是由操作疏忽导致的微生物污染引起的还是由样品的实际污染引起的。

IV. STERILITY TESTING无菌检测
On 10/11/91, the Agency published a proposed rule regarding the manufacture of drug products by aseptic processing and terminal sterilization. A list of contaminated or potentially contaminated drug products made by aseptic processing and later recalled was also made available. Many of the investigations/inspections of the recalled products started with a list of initial sterility test failures. FDA review of the manufacturers production, controls, investigations and their inadequacies, coupled with the evidence of product failure (initial sterility test failure) ultimately led to the action.
在1991年11月10日，FDA公布了一篇有关无菌生产制剂和最终灭菌制剂生产的议案。其中列举了一些无菌生产，但受到污染或者有可能被污染，后来被召回的一些制剂的名单。大多数对这些召回产品的调查都是从最初的无菌检测失败开始的。FDA对厂家的生产、质量控制、调查和失误的调查，以及产品质量事故的证据（无菌检测失败），最终导致了产品的召回。
The USP points out that the facilities used to conduct sterility tests should be similar to those used for manufacturing product. The USP states, "The facility for sterility testing should be such as to offer no greater a microbial challenge to the articles being tested than that of an aseptic processing production facility". Proper design would, therefore, include a gowning area and pass-through airlock. Environmental monitoring and gowning should be equivalent to that used for manufacturing product.
USP指出用于做无菌检测的设施应与用于生产的设施相同。USP中提到“与无菌生产的设施一样，用于无菌检测的设施也应进行微生物挑战试验和尘埃粒子监测”。对无菌检测设施的设计应考虑到洁净服和缓冲间。环境监测和洁净服应与产品生产的相一致。
Since a number of product and media manipulations are involved in conducting a sterility test, it is recommended that the inspection include actual observation of the sterility test even though some companies have tried to discourage inspection on the grounds that it may make the firms analyst nervous. The inspection team is expected to be sensitive to this concern and make the observations in a manner that will create the least amount of disruption in the normal operating environment. Nevertheless, such concerns are not sufficient cause for you to suspend this portion of the inspection.
由于在做无菌检测过程中要处理大量的产品和培养基，我们建议应实地检查无菌检测的操作，不过许多公司都会以当场操作会引起操作人员紧张为由阻止检查。检查组应该特别注意那些会对正常的操作环境产生破坏的操作，虽然这些方面还不足以使这部分的检查不合格。
One of the most important aspects of the inspection of a sterility analytical program is to review records of initial positive sterility test results. Request lists of test failures to facilitate review of production and control records and investigation reports. Particularly, for the high risk aseptically filled product, initial positive sterility test results and investigations should be reviewed. It is difficult for the manufacturer to justify the release of a product filled aseptically that fails an initial sterility test without identifying specific problems associated with the controls used for the sterility test.
检查无菌检测过程的一个重要方面就是检查初次实验中结果为阳性的那些记录。索要一份阳性结果检测的清单有助于检查生产和控制记录以及调查报告。对那些高风险的无菌灌装制剂，尤其要检查检测结果为阳性的批次及对此展开的调查研究记录。当无菌灌装制剂的初次检测结果为阳性时，生产厂家如不能确定是由无菌检测控制过程引起的，那么是很难确保可以将产品正常放行。
Examine the use of negative controls. They are particularly important to a high quality sterility test. Good practice for such testing includes the use of known terminally sterilized or irradiated samples as a system control. Alternatively, vials or ampules filled during media fills have also been used.
应检查使用阴性对照的过程。阴性对照对于无菌检测来说是很重要的。阴性对照最好是采用已高温灭菌或辐照灭菌的样品作为对照组。或者，也可以采用在培养基灌装过程中灌装安瓶或小瓶的方法。
Be especially concerned about the case where a manufacturer of aseptically filled products has never found an initial positive sterility test. While such situations may occur, they are rare. In one case, a manufacturers records showed that they had never found a positive result; their records had been falsified. Also, the absence of initial positives may indicate that the test has not been validated to demonstrate that there is no carryover of inhibition from the product or preservative.
要特别注意那些生产无菌灌装制剂却从来没有出现过初次无菌检测阳性结果的厂家，因为这种情况是很少见的。如果真的出现这种情况，那么他们的记录很有可能是伪造的。同样，无阳性结果也有可能是该检测方法未对产品或防腐剂本身对细菌的抑制作用进行验证。
Inspect robotic systems or isolation technology, such as La Calhene units used for sterility testing. These units allow product withdrawal in the absence of people. If an initial test failure is noted in a sample tested in such a system, it could be very difficult to justify release based on a retest, particularly if test controls are negative.
应检查自动操作系统或者隔离系统，如La Calhene公司的无菌隔离系统。这些设备可以达到无人操作。如果在这种系统中操作的无菌检测结果仍为阳性，那么即使通过复验也很难将产品放行，尤其在阴性对照试验结果为阴性的情况下。
Evaluate the time period used for sterility test sample incubation. This issue has been recently clarified. The USP states that samples are to be incubated for at least 7 days, and a proposal has been made to change the USP to require a period of 14 days incubation. You are expected to evaluate the specific analytical procedure and the product for the proper incubation period. Seven days may be insufficient, particularly when slow growing organisms have been identified. Media fill, environmental, sterility test results and other data should be reviewed to assure the absence of slow growing organisms. Also, you should compare the methods being used for incubation to determine if they conform to those listed in approved or pending applications.
应对样品的培养时间进行评价，有关这个方面的规定最近刚被确实。USP规定无菌检测样品至少要培养7天，有人建议将时间延长至14天。样品培养时间的长短应该由产品的性能和无菌检测的方法决定。7天有可能是不够的，尤其是当有生长缓慢的菌存在的时候。应对培养基灌装、检测环境、和无菌测试的结果进行回顾，确保不存在生长缓慢的细菌。同样，要对细菌培养的方法进行比较，确定是否符合经核准的或待申请的列表上的方法。

V. METHODOLOGY AND VALIDATION OF TEST PROCEDURES方法学与验证
Determine the source of test procedures. Manufacturers derive test procedures from several sources, including the USP, BAM and other microbiological references. It would be virtually impossible to completely validate test procedures for every organism that may be objectionable. However, it is a good practice to assure that inhibitory substances in samples are neutralized.
要明确无菌检测方法的出处。生产厂商会参考许多种方法，包括USP，BAM和其它微生物参考资料。实际上是不可能对所有的致病菌的检测方法都进行完全的验证。不过，检测方法最好要确保样品中的抑菌剂能被中和。 
During inspections, including pre-approval inspections, evaluate the methodology for microbiological testing. For example, we expect test methods to identify the presence of organisms such as Pseudomonas cepacia or other Pseudomonas species that may be objectional or present a hazard to the user. Where pre-approval inspections are being conducted, compare the method being used against the one submitted in the application. Also verify that the laboratory has the equipment necessary to perform the tests and that the equipment was available and in good operating condition on the dates of critical testing.
在检查过程中，也包括批准前的检查，应对微生物检测的方法学进行评价。例如，检测方法应能鉴别出洋葱假单胞菌或其他假单胞菌等致病菌属。在进行批准前的检查时，应将现场使用的方法与企业申报资料时所报的方法进行比较。同时也要确认实验室是否有做这些实验需要的设备，这些设备是否可用，在做实验的期间的状态是否良好。
The USP states that an alternate method may be substituted for compendial tests, provided it has been properly validated as giving equivalent or better results.
USP规定可以采用其它方法代替药典中规定的方法，但是要经过详细的验证证明两种方法具有等同性或者比规定的方法更好。
You may find that dehydrated media are being used for the preparation of media. Good practice includes the periodic challenge of prepared media with low levels of organisms. This includes USP indicator organisms as well as normal flora. The capability of the media to promote the growth of organisms may be affected by the media preparation process, sterilization (overheating) and storage. These represent important considerations in any inspection and in the good management of a microbiology laboratory.
在制备培养基时会使用到脱水的培养基，应对制备好的培养基定期做微生物挑战试验。其中包括USP中的微生物指示剂，还有正常菌种。培养基的制备过程、灭菌（过热）过程和储存过程都会影响到培养基培养微生物的能力。这些问题在检查时都应引起重视，同时对于一个管理良好的微生物实验室来说，也应充分考虑到这些因素。

VI. DATA STORAGE数据存储
Evaluate the test results that have been entered in either logbooks or on loose analytical sheets. While some manufacturers may be reluctant to provide tabulations, summaries, or printouts of microbiological test results, this data should be reviewed for the identification of potential microbial problems in processing. When summaries of this data are not available the inspection team is expected to review enough data to construct their own summary of the laboratory test results and quality control program.
微生物测试结果可以写在实验日志或者活页纸上，并进行分析。不过一些生产企业不能提供表格、汇总或者其它反应微生物测试结果的打印物，在进行鉴别潜在存在的微生物问题时这些数据是要用来作回顾分析的。当数据的汇总没有时，检查组应检查足够多的数据对实验室的检测结果和质量控制进行汇总评价。
Some laboratories utilize preprinted forms only for recording test data. Some laboratories have also pointed out that the only way microbiological test data could be reviewed during inspections would be to review individual batch records. However, in most cases, preprinted forms are in multiple copies with a second or third copy in a central file. Some companies use log-books for recording data. These logbooks should also be reviewed.
一些实验室利用预先打印好的表格来记录测试数据，检查过程中也有实验室指出只能在单个的批记录里才能看到微生物检测数据。然而，大多数情况是，预先印好的表格有很多复印件。一些企业采用日志本的方式来记录数据，对这些日志本也应进行检查。
Additionally, many manufacturers are equipped with an automated microbial system for the identification of microorganisms. Logs of such testing, along with the identification of the source of the sample, are also of value in the identification of potential microbial problems in processing.
另外，许多企业还配备了自动化的微生物鉴别系统。这类系统所进行的测试及鉴别的日志对于处理潜在微生物问题时也是很有用处的。
The utilization of automated systems for the identification of microorganisms is relatively common in the parenteral manufacturer where isolates from the environment, water systems, validation and people are routinely identified.
注射剂生产厂家常常会采用这种自动化的微生物鉴别系统，可以与环境、水处理系统和人员进行有效隔离。
Microbiologists in our Baltimore District are expert on the use of automated microbial analytical systems. They were the first FDA laboratory to use such equipment and have considerable experience in validating methods for these pieces of equipment. Contact the Baltimore District laboratory for information or questions about these systems. Plants with heavy utilization of these pieces of equipment should be inspected by individuals from the Baltimore District laboratory.
巴尔的摩实验室的微生物学家是使用自动化微生物分析系统的专家。他们是首批使用此类设备的FDA实验室，并且在对这些仪器的验证上有丰富的经验。对于这类分析系统的信息和问题可以直接联系巴尔的摩的实验室。如有些厂家使用大型的这类设备，就应该派巴尔的摩的实验室的人员参与检查。

VII. MANAGEMENT REVIEW质量管理
Microbiological test results represent one of the more difficult areas for the evaluation and interpretation of data. These evaluations require extensive training and experience in microbiology. Understanding the methodology, and more importantly, understanding the limitations of the test present the more difficult issues. For example, a manufacturer found high counts of Enterobacter cloacae in their oral dosage form product derived from a natural substance. Since they did not isolate E. coli, they released the product. FDA analysis found E. cloacae in most samples from the batch and even E. coli in one sample. In this case management failed to recognize that microbiological contamination might not be uniform, that other organisms may mask the presence of certain organisms when identification procedures are performed, and that microbiological testing is far from absolute. The inspection must consider the relationship between the organisms found in the samples and the potential for the existence of other objectionable conditions. For example, it is logical to assume that if the process would allow E. cloacae to be present, it could also allow the presence of the objectionable indicator organism. The microbiologist should evaluate this potential by considering such factors as methodology, and the growth conditions of the sample as well as other fundamental factors associated with microbiological analysis.
分析和解释微生物检测数据是确定检测结果中比较困难的一个方面，要求在微生物学方面有很丰富的知识和经验。要理解微生物检测的方法，更重要的是要理解该方法存在的局限性，而这往往又是难度比较大的。例如，生产厂家发现在天然药物的口服制剂中存在较大量的E.cloacae菌，由于他们没有检测出大肠杆菌，就将该批药品放行了。FDA检测时发现在这批的大多数样品中发现E.cloacae菌，在一个样品中甚至发现了大肠杆菌。在这个案例中，该企业没有认识到微生物的污染是不均一的，微生物测试方法是存在缺陷的，而在做鉴别测试时，其它微生物的存在会掩盖特定的微生物。检查时应了解样品中发现的微生物和可能存在的致病菌的关系。例如，如果操作过程中有E.cloacae菌存在，那么也有可能会存在指示剂能检测出的致病菌存在。生物学家应考虑一些因素如方法学、微生物在样品中的生长状态、其它的一些与微生物分析有关的基础性因素来评价这些潜在的因素。
Evaluate managements program to audit the quality of the laboratory work performed by outside contractors.
应评价外部委托实验室的管理程序来审计他们的工作质量。

VIII. CONTRACT TESTING  LABORATORIES委托检测实验室
Many manufacturers contract with private or independent testing laboratories to analyze their products. Since, these laboratories will conduct only the tests that the manufacturer requests, determine the specific instructions given to the contractor. Evaluate these instructions to assure that necessary testing will be completed. For example, in a recent inspection of a topical manufacturer, total plate count and testing for the USP indicator organisms were requested. The control laboratory performed this testing only and did not look for other organisms that would be objectionable based on the products intended use.
许多生产厂家会委托私人或者独立的实验室进行微生物检测。由于这些实验室只仅限于完成厂家要求的项目，因此要确定一份给委托实验室的特定的操作要求。应评价这些要求能保证必要的测试都能够进行。例如，在最近一次检查中，产品为局部外用药，要求做的检测项目为细菌总数和USP规定的指示微生物测试。委托实验室就只做了这些测试，却没有从产品的预期用途出发寻找有可能存在的其它致病菌。
Analytical results, particularly for those articles in which additional or retesting is conducted, should be reviewed. Test reports should be provided to the manufacturer for tests conducted. It is not unusual to see contract laboratories fail to provide complete results, with both failing as well as passing results.
委托实验室在检测后应提供检测报告，但是不管检测结果是合格的还是不合格的，常常会存在委托实验室不能提供完整的检测报告的现象。因此，应对检测结果尤其是有额外测试或者复测的项目进行检查。
Bacteriostasis/fungiostasis testing must be performed either by the contract lab or the manufacturer. These test results must be negative otherwise any sterility test results obtained by the contractor on the product may not be valid.
委托实验室或者生产厂家必须进行抑菌/抑真菌测试。这些测试结果必须为阴性，否则任何无菌测试的结果都是无效的。

       文章来源：药品微生物检测

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