应《网络安全法》要求，自2017年10月1日起，未进行实名认证将不得使用互联网跟帖服务。为保障您的帐号能够正常使用，请尽快对帐号进行手机号验证，感谢您的理解与支持！

24小时热门版块排行榜    

小木虫论坛-学术科研互动平台 » 生物医药区 » 药学 » USP中关于沉降菌检验频率
51/1返回列表
查看: 1279  |  回复: 11
只看楼主@他人 存档 新回复提醒 (忽略) 收藏    在APP中查看
当前主题已经存档。
当前只显示满足指定条件的回帖，点击这里查看本话题的所有回帖

feng1619

金虫 (小有名气)

小木虫管家

[交流] USP中关于沉降菌检验频率

各位专家，我国GMP规定沉降菌与浮游菌只检一样即可，请问USP是如何规定的，浮游菌在各种环境级别的检测频率是多少？100000级的标准是多少？
回复此楼

» 猜你喜欢
我是管家,有事情找我!
1楼2008-07-25 08:25:42
已阅   回复此楼   关注TA 给TA发消息 送TA红花 TA的回帖

huigenghao

至尊木虫 (著名写手)
表 5. 以cfu表示的控制环境中工作人员活动表面洁净指导方针。
级别                每接触板的cfu*

SI         U.S. 习惯                手套         工作人员衣着
& 装束
M3.5        100                3        5
M5.5        10,000                10        20
*  见表 4 下注 (*)。


活性空气播散微生物定量的方法学和仪器操作
控制环境中空气播散微生物能够对这些区域内半成品或最终产品的微生物质量起到影响。这一观点已被科学家们所普遍接受。另外人们也普遍接受这种观点，即空气播散微生物的估测也会受到执行这些分析所用仪器和相关操作的影响。因此，当方法和仪器有所变化时，应当确定其所获结果的一般等价转换。我们期待将来的技术进步可以带来革新，以提供比现有可用方法更高的精密度和敏感度，并且可用确定微生物数量检测中的变化绝对值。
目前，美国制药和医用器材工业最常用的取样器为嵌入式和离心取样器。以下所列取样器均可通过商业购买得到，仅作为信息提供。对特定取样器的选择、购买和充分利用则由使用者负责。
Slit-to-Agar空气取样器 (STA)— 这一取样器是依据多种控制环境表 3的微生物指导方针的一种仪器。其动力来源为附属可控真空装置。空气通过一个标准化的缝隙进入缝隙下面设置的缓慢回转式有盖培养皿，皿内含有营养琼脂。空气中的颗粒物质具有足够的质量撞击琼脂表面，使得活菌能够在其表面生长。通常用吸入稀疏空气的方法来减小空气层流区域的干扰。
滤网取样器（Sieve Impactor）— 此装置包括一个容器，可以调节含营养琼脂的有盖培养皿。装置的盖子有穿孔，穿孔的大小是预先设计好的。真空泵通过盖子的穿孔抽取已知体积的空气，空气中含有微生物的颗粒就与有盖培养皿内的琼脂培养基碰撞。一些取样器具有一系列串联级有孔容器，其穿孔按大小降序排列。这些装置能够依照尺寸范围分级测量含活性微生物的颗粒样品，因为颗粒是经过有大小尺寸的穿孔而到达琼脂平板表面的。
离心取样器（Centrifugal Sampler）— 此装置包括一个推进器或涡轮，以推动已知体积的空气进入装置内部，然后向外推进空气使其与独立设置在一个柔韧塑料基板上的营养琼脂条碰撞。
无菌微生物房（Sterilizable Microbiological Atrium）— 此装置是单孔滤网打入器的一种变型。装置的盖子含有均匀分布的约0.25英寸的小口。装置的基底适合于一个含营养琼脂的有盖培养皿。由真空泵来控制通过装置的空气运动，并可以应用多重装置控制中心和远距离取样探针。
表面空气系统取样器（Surface Air System Sampler）— 这是一种整合装置，包括一个适合琼脂接触板的进入部分。紧接着接触板的后面，是一个传动器和涡轮，可以推动空气穿过装置中琼脂接触板的有孔盖子，以及穿过传动器远端。也可以有多重包埋组合。
凝胶薄膜过滤取样器（Gelatin Filter Sampler）— 这一装置包括一个带有延长管的真空泵，延长管的终端是一个滤纸夹，此末端可以被放置于遥远的关键性空间。滤纸含有无规则明胶纤维，对空气播散微生物起到防卫作用。经过特定的暴露时间后，滤纸被无菌的移开，并用适当的稀释剂溶解，然后涂于适当的琼脂培养基上进行微生物含量的评价。
沉降皿（Settling Plates）— 作为一种简单和廉价的方法，仍被广泛用于延长暴露时间的环境品质评估。但是开放性琼脂填充培养皿或沉降皿的方法，不能用于对关键环境进行微生物污染的品质评估。
机械空气取样器的一个主要的缺陷是对被取样空气样本量的限制。如果一个控制环境的空气微生物水平期望值为不高于3 cfu 每立方米，那么就需要对几个立方米的空气进行测试，进而得到准确度和精确度合乎给定标准的结果。通常这是不切实际的。为了显示环境中存在的微生物数量不随时间而增加，可能就需要通过延长取样时间来确定取样时间是否是一个限制性因素。具代表性的有，slit-to-agar取样器具有每分钟80升的取样能力(对于表面空气系统，此能力有时可能会更高)。如果检测1立方米的空气，接着将需要暴露时间为15分钟。用这过多的15分钟取样时间，对于获得代表性的环境样品，可能是必需的。尽管报导有一些取样器，其取样体积比率能达到很高，可是这些情形中存在的对任何关键区域气流模式的潜在破坏性或是能够增加污染可能性的紊流形成，都应该给予考虑。
对于离心空气取样器，许多前期的研究表明，所取样品显示了对较大颗粒的选择性。这种类型取样器的应用，可能会由于其固有的选择性，引起比其它类型空气取样器更高的空气播散计数。
当选择离心取样器时，应当考虑到取样器对取样位置的控制区域气流线性的影响。如果忽略所用取样器的类型，则远距离探针的应用需要检测其额外的配管对活性空气播散计数没有不良影响。 如有影响，则应设法消除；如果无法消除，则应当在报告结果时引进校正系数。

测量控制环境内活性微生物污染表面取样的仪器和方法学
微生物环境控制程序的另一组成部分是这些环境中仪器、设备以及工作人员着装的表面取样。在制药工业中，表面取样方法和程序的标准化程度还不及空气取样程序的标准化程度广泛。3 为使对关键性操作的影响最小化，表面取样应该在该操作的结尾进行。表面取样可以通过应用接触平板或者水刷方法来完成。表面监测通常在于产品有关联的区域或与这些区域相邻近的区域表面进行。装有营养琼脂的接触平板通常应用于规则的或平坦的表面取样，并且在给定温度下直接孵育适当时间以对活菌进行定量检测。对于真菌、孢子等的特殊定量检测应当用专门的琼脂。
水刷方法可以用于不规则表面的取样，尤其是仪器表面。在规则表面，水刷法可作为接触平板方法的补充。取样后，将水刷置于适当的稀释剂冲之中，然后在适当的营养琼脂上或其中接种适当量以进行微生物计数评估。将要被刷的区域用适当大小的无菌模板确定。通常其大小在 24 到30 cm2范围内。对报告的每接触板或每刷进行微生物学评估。

微生物取样或定量用培养基及稀释剂
控制环境中用于微生物取样或定量的培养基类型是液体还是固体，取决于所用仪器和操作的过程。当需要固体培养基时，一般选用通用的大豆-酪蛋白消化琼脂培养基。其它固体和液体培养基见下表。
液体培养基*
固体培养基*

胰蛋白胨盐        大豆-酪蛋白消化琼脂
胨水        营养琼脂
缓冲盐水        胰蛋白胨葡萄糖浸液琼脂
缓冲明胶        卵磷脂琼脂
浓缩缓冲明胶        脑心浸液琼脂
脑心浸液        琼脂平板
大豆-酪蛋白培养基       
*  液体和固体培养基已用有效方法进行过灭菌处理.
这些培养基的脱水型都可以在市场上购买到。它们的即用型也能够买得到。当控制区域用了消毒剂或抗生素时，应当考虑应用具有适当灭活剂的培养基。
可以从上表中选择培养基，如果确证其能够有效到达预期目的。

来自环境控制程序的微生物隔离群的鉴别
环境控制程序包括对从样品中获得的菌丛进行适当标准的鉴别。具有控制环境中一般菌株的知识，能帮助我们预先确定被监测设备通常的微生物菌株；评估洁净和清洁卫生处理程序、方法及试剂的有效性；并恢复一些方法。通过鉴别程序收集的信息，在对污染源的调查中也是有用的，尤其是当其超过行动标准时。
鉴别从关键区域以及紧邻关键区域得到的隔离群，应当优先于对非关键区域微生物的鉴别。鉴别方法应当校验，而且即用试剂盒的质量与其预期目的相当。(见环境控制程序设计和实施中的相关关键因素)。

洁净室和其他控制环境中无菌填充产品微生物状况的操作评估
控制环境的监测是通过适当的环境监测程序进行的。为了确保得到最小生物负载，控制环境中微生物状况评估的额外信息，可以通过应用培养基填充来获得。一个可接受的培养基填充可以在生产线上对点及时成功模拟出产品的流程。然而，其它的因素也是重要的，比如适当的设备构建、环境监测以及人员培训。
当一套无菌操作系统被制定和安装时，通过至少连续三次成功的培养基填充以检测微生物状况的合格性通常是必需的。培养基填充是用生长培养基替代原产品，以检测微生物的生长。在培养基填充程序的发展过程中值得注意的问题如下：培养基填充过程、培养基的选择、填充体积、孵育时间和温度、填充装置的检查、文件证明、结果解释以及需要的可能改善行动。
由于设计培养基填充是为了模拟特定产品的无菌过程，使得培养基填充过程中，正常产品生产流程条件对其的影响显得重要了。这包括整个的工作人员、所有的加工处理步骤以及构成一般产品流程的原料。培养基填充生产期间，应当计划发生在实际产品生产流程期间的多种初始文件性干涉(如改变填充针、固定组件塞)。
为了增加安全域，可以选择性的进行可能条件的联合应用。实例可能包括频繁启动和停止顺序、非预期的处理系统修复、滤纸的替换等等。取得无菌操作资格不需要每一产品的检测，而应当对每一生产线进行检测。容器的几何形状(容器的大小和其开启)和流水线的速度都是无菌操作线上的可变因素，因此应当在生产线质控上对这些因素进行适当的结合，最好是在终端结合。产品应用的原则应当形成文件性指导。
1987年 FDA关于通过无菌操作生产无菌药物制剂的指导方针指出，培养基填充流程应覆盖对于生产线/产品/容器结合的所有生产换岗。这一指导方针应不仅仅被认为是培养基填充流程的质控，而且应看成是周期性再评估或再生效的指导。培养基填充程序还应当模拟扩展运行的生产实践。这可以通过在产品生产运作末端进行培养基填充运作来实现。
通常，像大豆酪蛋白牛肉汤这种已经用一系列水平低于100 cfu/unit的指示微生物 (见 无菌检查（Sterility Tests）á71ñ进行过促生长检验的通用丰富培养基，可以被应用。来自将要进行无菌操作生产的控制环境中的隔离群也可以被应用。培养基的无菌操作之后，填充容器被置于22.5 ± 2.5 或32.5 ± 2.5 进行孵育。所以填充培养基的容器至少应当孵育14天。如果培养基样品的孵育温度有两个，那么这些填充容器在每个温度下至少要孵育7天。孵育过后，应当对培养基填充容器进行生长检查。培养基填充隔离群以属进行鉴别，如果出于调查污染源为目的的需要，可能的话要鉴别到种。
在进行培养基填充时关键性问题有：使无菌操作质量合格的填充数量，每一培养基填充的单位数量，对结果的解释以及改善行动的实行。据以往经验，常在质控初始或设备初启时采取3个培养基填充运行来证明无菌操作线程的连贯性。0.1%污染率是一个成功培养基填充运行的可接受标准，用于证明污染率不超过0.1%的最小单位数至少应为3,000。应当强调指出， 美国以及其它国家的的许多生产商在单次培养基填充运行时填充单位超过了3,000。4 中试工厂用于制备临床批产品的设备，可以用较小的培养基填充。
许多国际性文件(即ISO 和EU-GMP)也已经引用了3,000培养基填充单位中期望零阳性检出在95%置信度。可是，公认的为了确证过程中实测污染率的统计真实性，就需要进行重复的培养基填充运行。
PDA 技术专题论文17期4的“当前无菌制造业实践的调查”表明，许多生产商认为他们的无菌操作过程能够使污染率低于0.1%
既然洁净室最关键的污染源是工作人员，那么在培养基填充过程中能够对相关生产活动中污染事件起到帮助的可视性文件就应得到支持。无菌测试隔离系统的广泛应用，已经表明无菌操作中去除人员确实能减少污染的发生。

目前出现的先进无菌操作技术综述
由于无菌操作中人员的参与和介入与产品污染潜在性之间存在密切的联系，所以设计并运行了可以使人员和关键区域相隔绝的生产系统。研究减少污染可能性的方法包括自动化装备、阻挡层以及隔离系统。采用这些先进无菌操作策略的设备现已投入运行。在应用这些设备的地方，人员已经被完全排除在关键区域之外，那么基于颗粒和环境微生物监测需求的洁净室分类的必需性可能就会明显的减少了。
以下是关于一些目前应用于无菌操作用以减少污染的系统的定义：
阻挡层（Barriers）— 在无菌操作系统里，阻挡层是一种装置，用来限制操作人员与阻挡层内被隔离无菌区域之间的接触。这些系统用于无菌填充，同时也用于医院药房、实验室以及照管动物设备。阻挡层可以是没有灭过菌的，并且不能总是有准许没有暴露在周围环境中的原料进出/出通行的传递系统。阻挡层可以是围住关键生产区域的塑料屏障，也可以是在现代无菌填充设备外建立的坚硬的外壳。阻挡层也可以结合一些元素，如手套孔、不完全工作服以及快速传递通道等。
Blow/Fill/Seal— 这种类型的系统将容器吹成型、产品填充以及单片设备加封操作相结合。从微生物学角度来看，使容器成型、装入无菌产品以及封盖的形成和应用这系列连续事件，达到了连续的无菌操作并使其于环境中的暴露最小化。这些系统的存在已有大约30年的历史，并且显示出使污染率到达低于0.1%的能力。当综合和分析组和培养基填充数据时，blow/fill/seal系统的污染率能够达到0.001%。
隔离器（Isolator）— 这一技术可有双重目的应用。一个是保护产品免受来自环境中的污染，包括装入和封闭过程中的人员方面污染；另一个是保护人员免受正在制造的有毒或有害产品的影响。
赞一下 回复此楼
10楼2008-07-27 12:00:55
 已阅   回复此楼   关注TA 给TA发消息 送TA红花 TA的回帖
查看全部 12 个回答

feng1619

金虫 (小有名气)

小木虫管家
奇怪，怎么只有人看，没有人回答呢？
赞一下 回复此楼
我是管家,有事情找我!
2楼2008-07-25 15:24:28
 已阅   回复此楼   关注TA 给TA发消息 送TA红花 TA的回帖

huigenghao

至尊木虫 (著名写手)
★ ★ ★ ★ ★ ★ ★ ★ ★ ★
feng1619(金币+10,VIP+0):非常感谢你的热心和你提供的资料！
再usp 116节有明确的说明，下面是29版的内容，请你参考

U.S. PHARMACOPEIA         USP29                                 
1116 MICROBIOLOGICAL EVALUATION OF CLEAN ROOMS AND OTHER CONTROLLED ENVIRONMENTS                               
The purpose of this informational chapter is to review the various issues that relate to aseptic processing of bulk drug substances, dosage forms, and in certain cases, medical devices; and to the establishment, maintenance, and control of the microbiological quality of controlled environments.                               
This chapter includes discussions on (1) the classification of a clean room based on particulate count limits; (2) microbiological evaluation programs for controlled environments; (3) training of personnel; (4) critical factors in design and implementation of a microbiological evaluation program; (5) development of a sampling plan; (6) establishment of microbiological Alert and Action levels; (7) methodologies and instrumentation used for microbiological sampling; (8) media and diluents used; (9) identification of microbial isolates; (10) operational evaluation via media fills; and (11) a glossary of terms. Excluded from this chapter is a discussion of controlled environments for use by licensed pharmacies in the preparation of sterile products for home use, which is covered under Pharmaceutical Compounding—Sterile Preparations 797.                               
There are alternative methods to assess and control the microbiological status of controlled environments for aseptic processing. Numerical values included in this chapter are not intended to represent absolute values or specifications, but are informational. Given the variety of microbiological sampling equipment and methods, one cannot reasonably suggest that the attainment of these values guarantees the needed level of microbial control or that excursions beyond values in this chapter indicate a loss of control. The improper application of microbiological sampling and analysis may cause significant variability and the potential for inadvertent contamination. Sampling media and devices, and methods indicated in this chapter, are not specifications but only informational.                               
A large proportion of sterile products are manufactured by aseptic processing. Because aseptic processing relies on the exclusion of microorganisms from the process stream and the prevention of microorganisms from entering open containers during filling, product bioburden as well as microbial bioburden of the manufacturing environment are important factors relating to the level of sterility assurance of these products.                               
                               
Establishment of Clean Room Classifications                               
The design and construction of clean rooms and controlled environments are covered in Federal Standard 209E. This standard of air cleanliness is defined by the absolute concentration of airborne particles. Methods used for the assignment of air classification of controlled environments and for monitoring of airborne particulates are included. This federal document only applies to airborne particulates within a controlled environment and is not intended to characterize the viable or nonviable nature of the particles.                               
The application of Federal Standard 209E to clean rooms and other controlled environments in the pharmaceutical industry has been used by manufacturers of clean rooms to provide a specification for building, commissioning, and maintaining these facilities. However, data available in the pharmaceutical industry provide no scientific agreement on a relationship between the number of nonviable particulates and the concentration of viable microorganisms.                               
The criticality of the number of nonviable particulates in the electronic industry makes the application of Federal Standard 209E a necessity, while the pharmaceutical industry has a greater concern for viable particulates (i.e., microorganisms) rather than total particulates as specified in Federal Standard 209E. A definite concern for counts of total particulates in injectable products exists in the pharmaceutical industry (see Particulate Matter in Injections 788).                               
The rationale that the fewer particulates present in a clean room, the less likely it is that airborne microorganisms will be present is accepted and can provide pharmaceutical manufacturers and builders of clean rooms and other controlled environments with engineering standards in establishing a properly functioning facility.                               
Federal Standard 209E, as applied in the pharmaceutical industry is based on limits of all particles with sizes equal to or larger than 0.5 µm. Table 1 describes Airborne Particulate Cleanliness Classes in Federal Standard 209E as adapted to the pharmaceutical industry. The pharmaceutical industry deals with Class M3.5 and above. Class M1 and M3 relate to the electronic industry and are shown in Table 1 for comparison purposes. It is generally accepted that if fewer particulates are present in an operational clean room or other controlled environment, the microbial count under operational conditions will be less, provided that there are no changes in airflow, temperature, and humidity. Clean rooms are maintained under a state of operational control on the basis of dynamic (operational) data.                               
Table 1. Airborne Particulate Cleanliness Classes*                               
Class Name        Particles equal to and larger than 0.5 µm                       
SI        U.S.        (m3)        (ft3)       
        Customary                       
M1        —        10        0.283       
M1.5        1        35.3        1       
M2        —        100        2.8       
M2.5        10        353        10       
M3        —        1,000        28.3       
M3.5        100        3,530        100       
M4        —        10,000        283       
M4.5        1,000        35,300        1,000       
M5        —        100,000        2,830       
M5.5        10,000        353,000        10,000       
M6                1,000,000        28,300       
M6.5        100,000        3,530,000        100,000       
M7        —        10,000,000        283,000       
*  Adapted from U.S. Federal Standard 209E, September 11, 1992—“Airborne Particulate Cleanliness Classes in Clean Rooms and Clean Zones.”
赞一下(4人) 回复此楼
3楼2008-07-27 11:17:51
 已阅   回复此楼   关注TA 给TA发消息 送TA红花 TA的回帖

huigenghao

至尊木虫 (著名写手)
Importance of a Microbiological Evaluation Program for Controlled Environments                               
Monitoring of total particulate count in controlled environments, even with the use of electronic instrumentation on a continuous basis, does not provide information on the microbiological content of the environment. The basic limitation of particulate counters is that they measure particles of 0.5 µm or larger. While airborne microorganisms are not free-floating or single cells, they frequently associate with particles of 10 to 20 µm. Particulate counts as well as microbial counts within controlled environments vary with the sampling location and the activities being conducted during sampling. Monitoring the environment for nonviable particulates and microorganisms is an important control function because they both are important in achieving product compendial requirements for Particulate Matter and Sterility under Injections 1.                               
Microbial monitoring programs for controlled environments should assess the effectiveness of cleaning and sanitization practices by and of personnel that could have an impact on the bioburden of the controlled environment. Microbial monitoring, regardless of how sophisticated the system may be, will not and need not identify and quantitate all microbial contaminants present in these controlled environments. However, routine microbial monitoring should provide sufficient information to ascertain that the controlled environment is operating within an adequate state of control.                               
Environmental microbial monitoring and analysis of data by qualified personnel will permit the status of control to be maintained in clean rooms and other controlled environments. The environment should be sampled during normal operations to allow for the collection of meaningful data. Microbial sampling should occur when materials are in the area, processing activities are ongoing, and a full complement of operating personnel is on site.                               
Microbial monitoring of clean rooms and some other controlled environments, when appropriate, should include quantitation of the microbial content of room air, compressor air that enters the critical area, surfaces, equipment, sanitization containers, floors, walls, and personnel garments (e.g., gowns and gloves). The objective of the microbial monitoring program is to obtain representative estimates of bioburden of the environment. When data are compiled and analyzed, any trends should be evaluated by trained personnel. While it is important to review environmental results on the basis of recommended and specified frequency, it is also critical to review results over extended periods to determine whether trends are present. Trends can be visualized through the construction of statistical control charts that include alert and action levels. The microbial control of controlled environments can be assessed, in part, on the basis of these trend data. Periodic reports or summaries should be issued to alert the responsible manager.                               
When the specified microbial level of a controlled environment is exceeded, a documentation review and investigation should occur. There may be differences in the details of the investigation, depending on the type and processing of the product manufactured in the room. Investigation should include a review of area maintenance documentation; sanitization documentation; the inherent physical or operational parameters, such as changes in environmental temperature and relative humidity; and the training status of personnel involved. Following the investigation, actions taken may include reinforcement of training of personnel to emphasize the microbial control of the environment; additional sampling at increased frequency; additional sanitization; additional product testing; identification of the microbial contaminant and its possible source; and an evaluation of the need to reassess the current standard operating procedures and to revalidate them, if necessary.                               
Based on the review of the investigation and testing results, the significance of the microbial level being exceeded and the acceptability of the operations or products processed under that condition may be ascertained. Any investigation and the rationale for the course of action should be documented and included as part of the overall quality management system.                               
A controlled environment such as a clean zone or clean room is defined by certification according to a relevant clean room operational standard. Parameters that are evaluated include filter integrity, air velocity, air patterns, air changes, and pressure differentials. These parameters can affect the microbiological bioburden of the clean room operation. The design, construction, and operation of clean rooms varies greatly, making it difficult to generalize requirements for these parameters. An example of a method for conducting a particulate challenge test to the system by increasing the ambient particle concentration in the vicinity of critical work areas and equipment has been developed by Ljungquist and Reinmuller.1 First, smoke generation allows the air movements to be visualized throughout a clean room or a controlled environment. The presence of vortices or turbulent zones can be visualized, and the airflow pattern may be fine-tuned to eliminate or minimize undesirable effects. Then, particulate matter is generated close to the critical zone and sterile field. This evaluation is done under simulated production conditions, but with equipment and personnel in place.                               
Proper testing and optimization of the physical characteristics of the clean room or controlled environment is essential prior to completion of the validation of the microbiological monitoring program. Assurance that the controlled environment is operating adequately and according to its engineering specifications will give a higher assurance that the bioburden of the environment will be appropriate for aseptic processing. These tests should be repeated during routine certification of the clean room or controlled environment and whenever changes made to the operation, such as personnel flow, processing, operation, material flow, air-handling systems, or equipment layout, are determined to be significant.                               
                               
Training of Personnel                               
Aseptically processed products require manufacturers to pay close attention to detail and to maintain rigorous discipline and strict supervision of personnel in order to maintain the level of environmental quality appropriate for the sterility assurance of the final product.                               
Training of all personnel working in controlled environments is critical. This training is equally important for personnel responsible for the microbial monitoring program, where contamination of the clean working area could inadvertently occur during microbial sampling. In highly automated operations, the monitoring personnel may be the employees who have the most direct contact with the critical zones within the processing area. Monitoring of personnel should be conducted before or after working in the processing area.                               
Microbiological sampling has the potential to contribute to microbial contamination due to inappropriate sampling techniques. A formal personnel training program is required to minimize this risk. This formal training should be documented for all personnel entering controlled environments.                               
Management of the facility must assure that all personnel involved in operations in clean rooms and controlled environments are well versed in relevant microbiological principles. The training should include instruction on the basic principles of aseptic processing and the relationship of manufacturing and handling procedures to potential sources of product contamination. This training should include instruction on the basic principles of microbiology, microbial physiology, disinfection and sanitation, media selection and preparation, taxonomy, and sterilization as required by the nature of personnel involvement in aseptic processing. Personnel involved in microbial identification will require specialized training on required laboratory methods. Additional training on the management of the environmental data collected must be provided to personnel. Knowledge and understanding of applicable standard operating procedures is critical, especially those standard operating procedures relating to corrective measures that are taken when environmental conditions so dictate. Understanding of regulatory compliance policies and each individual's responsibilities with respect to good manufacturing practices (GMPs) should be an integral part of the training program as well as training in conducting investigations and in analyzing data.                               
The major source of microbial contamination of controlled environments is the personnel. Contamination can occur from the spreading of microorganisms by individuals, particularly those with active infections. Only healthy individuals should be permitted access to controlled environments.
赞一下 回复此楼
4楼2008-07-27 11:18:30
 已阅   回复此楼   关注TA 给TA发消息 送TA红花 TA的回帖
查看全部 12 个回答
普通表情 龙 兔 虎 猫 高级回复(可上传附件)
信息提示
关闭
请填处理意见
关闭