USP30-1211翻译-灭菌和无菌保证

1211STERILIZATION AND STERILITY ASSURANCE OF COMPENDIAL ARTICLES
灭菌和无菌保证纲要条款
This informational chapter provides a general description of the concepts and principles involved in the quality control of articles that must be sterile. Any modifications of or variations in sterility test procedures from those described under Sterility Tests 71should be validated in the context of the entire sterility assurance program and are not intended to be methods alternative to those described in that chapter.
报告章节规定涉及到条款质量控制总的概念描述和原则是必须是无菌的.
从无菌测试<71>的章节描述中,无菌保证程序的整个上下文中规定没有可选择的方法,任何有关无菌测试程序变更或修改应该得到验证.
Within the strictest definition of sterility, a specimen would be deemed sterile only when there is complete absence of viable microorganisms from it. However, this absolute definition cannot currently be applied to an entire lot of finished compendial articles because of limitations in testing. Absolute sterility cannot be practically demonstrated without complete destruction of every finished article.
在最严格的无菌定义里,仅当它不含有任何可存的微生物,样品才被认为无菌.然而, 因为测试的局限性，这个绝对的定义不能普遍应用到整个纲要条款中。

实际上每个灭菌的物品没有完全的破坏，绝对无菌性不能得到论证。

The sterility of a lot purported to be sterile is therefore defined in probabilistic terms, where the likelihood of a contaminated unit or article is acceptably remote. Such a state of sterility assurance can be established only through the use of adequate sterilization cycles and subsequent aseptic processing, if any, under appropriate current good manufacturing practice, and not by reliance solely on sterility testing. The basic principles for validation and certification of a sterilizing process are enumerated as follows:
许多无菌状态据说是消过毒的,因此是或然论的定义污染的个体和物品可能性是在可以接受的细小范围的.这样一个无菌状态保证,仅能通过适当的灭菌周期和无菌的后续加工,即便要,在当前合适的GMP程序下,无菌测试也不可靠.一个无菌过程验证的基本原理如下:
1. Establish that the process equipment has capability of operating within
the required parameters. 确定加工设备的操作性能处在正确的参数.
2. Demonstrate that the critical control equipment and instrumentation
are capable of operating within the prescribed parameters for the
process equipment. 证明关键控制设备和使用仪器是能够在具有效力
参数下操作.
3. Perform replicate cycles representing the required operational range of
the equipment and employing actual or simulated product.
Demonstrate that the processes have been carried out within the
prescribed protocol limits and finally that the probability of microbial
survival in the replicate processes completed is not greater than the
prescribed limits. 执行可重复的循环表现在设备必需的操作范围和使用
真实或可模拟的产品.证明加工是在给定协议范围下执行,而且最后在可
重复的加工完成下微生物存活的可能性不能超过给定协议范围.
4. Monitor the validated process during routine operation. Periodically as
needed, requalify and recertify the equipment. 在常规的操作期间监控
验证程序.根据需要定期,重新证明和保证设备正常.
5. Complete the protocols, and document steps (1) through (4) above. 完
善协议,证明以上步骤1-4.
The principles and implementation of a program to validate an aseptic processing procedure are similar to the validation of a sterilization process. In aseptic processing, the components of the final dosage form are sterilized separately and the finished article is assembled in an aseptic manner.
验证一个无菌处理程序的法则和执行和灭菌过程确实认是相似的.在无菌处理中,最终剂量组成成分是分别灭菌的,最后物品的组装是在无菌方式完成的.
Proper validation of the sterilization process or the aseptic process requires a high level of knowledge of the field of sterilization and clean room technology. In order to comply with currently acceptable and achievable limits in sterilization parameters, it is necessary to employ appropriate instrumentation and equipment to control the critical parameters such as temperature and time, humidity, and sterilizing gas concentration, or absorbed radiation.灭菌过程或无菌程序正确确认要求较高的灭菌和绝对无尘室技术领域的知识水平. An important aspect of the validation program in many sterilization procedures involves the employment of biological indicators (see Biological Indicators 1035).在许多灭菌程序一个重要确实认纲要方面包括生物指示
剂的使用(参见生物指示剂<1035>-).The validated and certified process should be revalidated periodically; however, the revalidation program need not necessarily be as extensive as the original program.验证和鉴定的程序应当定时性地重新生效,然而,重新生效程序不必像原始文件那样广泛.
A typical validation program, as outlined below, is one designed for the steam autoclave, but the principles are applicable to the other sterilization procedures discussed in this informational chapter. The program comprises several stages.一个典型确实认程序如以下大纲,一个蒸汽高压灭菌锅设计而作,但原理也是适用于其它的灭菌程序,将在报告章节讨论.
The installation qualification stage is intended to establish that controls and other instrumentation are properly designed and calibrated. Documentation should be on file demonstrating the quality of the required utilities such as steam, water, and air.限定时期安装目的建立调节装置和其它的使用仪器能够得到适当设计和校准.文件能够记录下来备查证明要求效用的质量像蒸汽,水,空气.The operational qualification stage is intended to confirm that the empty chamber functions within the parameters of temperature at all of the key chamber locations prescribed in the protocol.可操作资格的时期是打算确认在
协议规定的所有关键锅室区域在温度参数以内的锅室功能.It is usually appropriate to develop heat profile records, i.e., simultaneous temperatures in the chamber employing multiple temperature-sensing devices.它通常适用于显示压力剖面的记录也就是在锅室使用多种温度敏感装置 A typical acceptable range of temperature in the empty chamber is ±1when the chamber temperature is not less than 121. 当锅室温度不少于121,一个典型的可接受的锅室温度幅度范围是±1.The confirmatory stage of the validation program is the actual sterilization of materials or articles. 确认程序确实认时期是原料或物品实际灭菌期.This determination requires the employment of
temperature-sensing devices inserted into samples of the articles, as well as either samples of the articles to which appropriate concentrations of suitable test microorganisms have been added, or separate BIs in operationally fully loaded autoclave configurations. 决定要求温度敏感装置嵌入到物品样本中,除了添加微生物测试需要的适当的物品浓度,或在操作上二度单独的装满物品的高压灭菌锅装置. The effectiveness of heat delivery or penetration into the actual articles and the time of the exposure are the two main factors that determine the lethality of the sterilization process. The final stage of the validation program requires the documentation of the supporting data developed in executing the program.热传递或穿透实际物品的效力和曝光时间是两个主要的因素决定灭菌程序的破坏性.确认的最终阶段需要执行程序的数据支持文件发展更新.
It is generally accepted that terminally sterilized injectable articles or critical devices purporting to be sterile, when processed in the autoclave, attain a 10–6 microbial survivor probability, i.e., assurance of less than 1 chance in 1 million that viable microorganisms are present in the sterilized article or dosage form. 一般公认的是末尾已灭菌的可注射的商品或关键设备声明是无菌的.在高压灭菌锅程序到达10–6细菌存活率也就是说保证在已灭菌的物品或配药形式上可存活的微生物一百万个不超过一个的几率.With heat-stable articles, the approach often is to considerably exceed the critical time necessary to achieve the 10–6
microbial survivor probability (overkill). 随着热稳定的物品,方法通常是相当超
越需要的临界温度到达10–6细菌存活率(过度杀灭).However, with an article where extensive heat exposure may have a damaging effect, it may not be feasible to employ this overkill approach.然而随着物品曝露在过度压力下可能有一个破坏性的作用. In this latter instance, the development of the sterilization cycle depends heavily on knowledge of the microbial burden of the product, based on examination, over a suitable time period, of a substantial number of lots of the presterilized product.在后面的例子,灭菌周期的发展很大程度上依靠基于检验,适当的时间周期,许多实质预先消毒的产品微生物负担的知识.
The D value is the time (in minutes) required to reduce the microbial population by 90% or 1 log cycle (i.e., to a surviving fraction of 1/10), at a specific temperature. D-值是在特效的温度下需要的时间(分钟)减少微生物群体,或大约90% or log1周期(也就是1/10存活部分) .Therefore, where the D value of a BI preparation of, for example, Bacillus stearothermophilus spores is 1.5 minutes under the total process parameters, e.g., at 121, if it is treated for 12 minutes under the same conditions, it can be stated that the lethality input is 8D. 然而一个BI,D值的地方,例如嗜热脂肪杆菌孢子在总的程序参数下为1.5分钟,举例来说,在121.下相同的条件下如果加热12分钟,规定的致命性的输入是8D. The effect of applying this input to the product would depend on the initial microbial burden. 应用这个输入产品的效果依靠最初的微生物耐热负荷.Assuming that its resistance to sterilization is equivalent to that of the BI, if the microbial burden of the product in question is 102 microorganisms, a lethality input of 2D yields a microbial burden of 1 (10theoretical), and a further 6D yields a calculated microbial survivor probability of 10–6. 假设它抵抗灭菌等同BI耐热能力,如果产品的微生物负担BI 可商榷的是102微生物,一个2D产量致命输入一个微生物1担子(理论上是10),进一步的6D 产量一个计算出的存活几率是10–6. (Under the same conditions, a lethality input of 12D may be used in a typical “overkill” approach.) (在相同的条件下,一个12D致死输入量可能是在一个典型
的过度杀伤方法)Generally, the survivor probability achieved for the article under the validated sterilization cycle is not completely correlated with what may occur with the BI. For valid use, therefore, it is essential that the resistance of the BI be greater than that of the natural microbial burden of the article sterilized.通常,有效的灭菌时间对物品而言存活概率取得，不能完全和BI 联系起来。

为有效利用，因此BI 的抗性是比已灭菌物品上的自然界微生物大。

It is then appropriate to make a worst-case assumption and treat the microbial burden as though its heat resistance were equivalent to that of the BI, although it is not likely that the most resistant of a typical microbial burden isolates will demonstrate a heat resistance of the magnitude shown by this species, frequently employed as a BI for steam sterilization. 于是进行最差的假设和测试微生物负担是合适的好象它的热抵抗力等同于BI ，尽管不是类似于大多数典型微生物担子隔离证明一个物种显示的巨大热抵抗。

对蒸汽灭菌而言，经常作为一个BI 。

In the above example, a 12-minute cycle is considered adequate for sterilization if the product had a microbial burden of 102 microorganisms. 在上面的例子如果产品有一个102微生物担子，12分钟的时间被认为是合适的灭菌时间。

However, if the indicator originally had 106 microorganisms content, actually a 10–2 probability of survival could be expected; i.e., 1 in 100 BIs may yield positive results. 然而，如果最初的指示剂有106微生物含量，实际上，预期10–2存活率，也就是说100 BIs 有1个，产生阳性结果。

This type of situation may be avoided by selection of the appropriate BI. Alternatively, high content indicators may be used on the basis of a predetermined acceptable count reduction.通过适当的BI选择，这个典型情况可以防止。

择二为一，高容量的指示剂可用于以预定的可接受的数量减少为基础。

The D value for the Bacillus stearothermophilus preparation determined or verified for these conditions should be reestablished when a specific program of validation is changed. Determination of survival curves (see Biological Indicators 1035), or what has been called the fractional cycle approach, may be employed to determine the D value of the biological indicator preferred
for the specific sterilization procedure. 当确认的特效程序改变时为这些条件决定或校验对嗜热脂肪杆菌预备的D值应当是重建.The fractional cycle approach, may also be used to evaluate the resistance of the microbial burden. Fractional cycles are studied either for microbial count-reduction or for fraction negative achievement. 部分时间方法也可以用来估计微生物担子抵抗力.These numbers may be used to determine the lethality of the process under production conditions. 在产品到达要求的情况下这些数字可以用来确定程序的致死量. The data can be used in qualified production equipment to establish appropriate sterilization cycles. A suitable biological indicator such as the Bacillus stearothermophilus preparation may be employed also during routine sterilization. 在具有资格的产品设备这数据能用来确定合适的灭菌时间.一个适当的微生物指示剂例如嗜热脂肪杆菌预备在常规的灭菌期间也可以使用.Any microbial burden method for sterility assurance requires adequate surveillance of the microbial resistance of the article to detect any changes, in addition to periodic surveillance of other attributes.除了定期监督其它品质,为无菌保证任何微生物担子方法要求适当物品微生物抗性监督探测任何改变.
METHODS OF STERILIZATION
灭菌方法
In this informational chapter, five methods of terminal sterilization, including removal of microorganisms by filtration and guidelines for aseptic processing, are described. 在这报告的章节描述,终端灭菌的五种方法,包括微生物清除,通
过过滤和无菌处理的指导.Modern technological developments, however, have led to the use of additional procedures. These include blow-molding (at high temperatures), forms of moist heat other than saturated steam and UV irradiation, as well as on-line continuous filling in aseptic processing. 然而,现代科技的发展已经引导附加程序的运用.这些包括吹塑法(在高温) The choice of the appropriate process for a given dosage form or component requires a high level of knowledge of sterilization techniques and information concerning any
effects of the process on the material being sterilized.1对一个给定的配药形式或成份的合适的程序选择要求灭菌技术和有关影响原料灭菌程序的信息的较高的知识水平。

Steam Sterilization
蒸汽灭菌
The process of thermal sterilization employing saturated steam under pressure is carried out in a chamber called an autoclave利用饱和水蒸汽在锅室下由压力携带的热灭菌方法叫高压灭菌锅。

It is probably the most widely employed sterilization process.2它是利用最广泛的灭菌程序。

The basic principle of operation is that the air in the sterilizing chamber is displaced by the saturated steam, achieved by employing vents or traps. 工作的基本原理是在灭菌室通过通风孔和携带物由饱和水蒸汽取代空气。

In order to displace air more effectively from the chamber and from within articles, the sterilization cycle may include air and steam evacuation stages. 为了更加有效率从锅室和物品里置换出空气，灭菌时间可以包括空气和水蒸汽排开时间。

The design or choice of a cycle for given products or components depends on a number of factors, including the heat lability of the material, knowledge of heat penetration into the articles, and other factors described under the validation program (see above). 给定的产品或成分的灭菌时间的设计或选择取决于很多因素，包括材料的热不稳定性，热渗透物品的知识，和在确认程序下描述的其它因素〔参见上述〕。

Apart from that description of sterilization cycle parameters, using a temperature of 121, the F0 concept may be appropriate. 除了灭菌时间参数描述外，使用温度为121，F0的概念可能是适合的。

The F0 , at a particular temperature other than 121, is the time (in minutes) required to provide the lethality equivalent to that provided at 121for a stated time.除了121,在特殊温度F0，是时间〔分钟〕要求在121适合即定时间提供使微生物带来致命性等同条件。

Modern autoclaves g比enerally operate with a control system that is significantly more
responsive than the steam reduction valve of older units that have been in service for many years.现代化高压灭菌锅通常带有控制系统操作，比服务很多年的旧式蒸汽降低阀是引起值得注目地反响。

In order for these older units to achieve the precision and level of control of the cycle discussed in this chapter, it may be necessary to upgrade or modify the control equipment and instrumentation on these units. 为了这些旧的单元到达精确和这章节讨论的时间控制水平，升级和修改控制装备以及这些单元的使用设备是必要的。

This modification is warranted only if the chamber and steam jacket are intact for continued safe use and if deposits that interfere with heat distribution can be removed. 仅如果为了持续地安全利用和驱除存放物干扰热分配，锅室和蒸汽套是完整无缺，修改被批准。

Dry-Heat Sterilization
干热灭菌
The process of thermal sterilization of Pharmacopeial articles by dry heat is usually carried out by a batch process in an oven designed expressly for that purpose.药典条款热灭菌程序通常通过在一个特别设计的烤炉进行干热来实现到达灭菌的目的。

A modern oven is supplied with heated, filtered air, distributed uniformly throughout the chamber by convection or radiation and employing a blower system with devices for sensing, monitoring, and controlling the critical parameters. 一个现代烤箱提供热，过滤过的空气，均一分布在锅室，通过利用一个吹风机系统装置传送或发散适用于感知，监测和控制临界参数。

The validation of a dry-heat sterilization facility is carried out in a manner similar to that for a steam sterilizer described earlier. Where the unit is employed for sterilizing components such as containers intended for intravenous solutions, care should be taken to avoid accumulation of particulate matter in the chamber. 干热灭菌设备确实认通过与早期的蒸汽灭菌器相似的方式实现。

为这灭菌成分例如用来盛装注射静脉内溶液的容器，应当注意防止锅室颗粒物质的积聚。

A typical acceptable range in temperature in the empty chamber is ±15
when the unit is operating at not less than 250.在空的锅室，一个典型可接受的温度范围是±15，当它工作时，温度不小于250。

In addition to the batch process described above, a continuous process is frequently employed to sterilize and depyrogenate glassware as part of an integrated continuous aseptic filling and sealing system. 除了以上描述的一炉程序外，一个连续的程序是频繁地使用灭菌和热原的玻璃器具作为一个综合的持续的无菌的添充物和密封系统的一部分。

Heat distribution may be by convection or by direct transfer of heat from an open flame. 热发送通过传送或从一个明火直接热传递。

The continuous system usually requires a much higher temperature than cited above for the batch process because of a much shorter dwell time. 因为一个较短的保压时间，连续的系统对锅炉程序通常要求比以上引证的更高的温度。

However, the total temperature input during the passage of the product should be equivalent to that achieved during the chamber process. 然而，在产品通过期间总的温度输入应当与锅室程序取得等效。

The continuous process also usually necessitates a rapid cooling stage prior to the aseptic filling operation.持续的程序通常也是使一个快速冷却阶段先于无菌填充物实成为必要。

In the qualification and validation program, in view of the short dwell time, parameters for uniformity of the temperature, and particularly the dwell time, should be established.在资格和确认程序，考虑到短的保压时间，温度的同样参数，特别是保压时间，应当确定。

A microbial survival probability of 10–12 is considered achievable for
heat-stable articles or components. An example of a biological indicator for validating and monitoring dry-heat sterilization is a preparation of Bacillus subtilis spores. Since dry heat is frequently employed to render glassware or containers free from pyrogens as well as viable microbes, a pyrogen challenge, where necessary, should be an integral part of the validation program, e.g., by inoculating one or more of the articles to be treated with 1000 or more USP Units of bacterial endotoxin. The test with Limulus lysate could be used to demonstrate that the endotoxic substance has been inactivated to not more
than 1/1000 of the original amount (3 log cycle reduction). For the test to be valid, both the original amount and, after acceptable inactivation, the remaining amount of endotoxin should be measured. For additional information on the endotoxin assay, see Bacterial Endotoxins Test 85 .
对热稳定物品或者成分，10–12的微生物的存活概率被认为可以实现。

对于干热灭菌确实认和监测，一个生物指示剂的例子就是枯草芽孢杆菌孢子的制备。

自从干热灭菌频繁地用于玻璃器具以及容器的的热原以及可活化的微生物的清除，除去热原是必要的，应当成为确认程序的主要部分，例如通过接种用1000或者更大USP单位的细菌内毒素处理过的一种或更多物品。

鲎试剂测试可以用于证明内毒素物质已经活性丧失到不超过原来总量的1/1000〔降低了3 log数量级〕。

由于该测试被证明有效，不管是原始量还是可接受的失活量，内毒素的残留量都应该测量。

关于内毒素分析的更多信息，参见细菌内毒素测试85 .
Gas Sterilization
气体灭菌法
The choice of gas sterilization as an alternative to heat is frequently made when the material to be sterilized cannot withstand the high temperatures obtained in the steam sterilization or dry-heat sterilization processes. The active agent generally employed in gaseous sterilization is ethylene oxide of acceptable sterilizing quality. Among the disadvantages of this sterilizing agent are its highly flammable nature unless mixed with suitable inert gases, its mutagenic properties, and the possibility of toxic residues in treated materials, particularly those containing chloride ions. The sterilization process is generally carried out in a pressurized chamber designed similarly to a steam autoclave but with the additional features (see below) unique to sterilizers employing this gas. Facilities employing this sterilizing agent should be designed to provide adequate post sterilization degassing, to enable microbial survivor monitoring, and to minimize exposure of operators to the potentially harmful gas.3
气体灭菌法作为一种替代在蒸汽和干热灭菌程序加热频繁地用于不能经受高温材料灭菌的方法。

通常用于气体灭菌的活性剂是有合格消毒质量的环氧乙烷。

这种灭菌作用剂的弊端有高度易燃的性质，除非混有适量的惰性气体，还有诱变特性，以及在处理过材料上的残留量引起中毒的可能性，特别是那些含有氯离子。

灭菌程序是在一个如高压蒸汽灭菌器设计但又有独有的使用该气体灭菌特点〔如下〕的加压空间内实现。

使用这种灭菌作用剂的设备应当被设计成能提供足够的灭菌脱气，以确定残存微生物检测，并尽量减少设备操作人员对潜在有害气体的暴露。

Qualification of a sterilizing process employing ethylene oxide gas is accomplished along the lines discussed earlier. However, the program is more comprehensive than for the other sterilization procedures, since in addition to temperature, the humidity, vacuum/positive pressure, and ethylene oxide concentration also require rigid control. An important determination is to demonstrate that all critical process parameters in the chamber are adequate during the entire cycle. Since the sterilization parameters applied to the articles to be sterilized are critical variables, it is frequently advisable to precondition the load to achieve the required moisture content in order to minimize the time of holding at the required temperature before placement of the load in the ethylene oxide chamber. The validation process is generally made employing product inoculated with appropriate (BIs) such as spore preparations of Bacillus subtilis. For validation they may be used in full chamber loads of product, or simulated product. The monitoring of moisture and gas concentration requires the utilization of sophisticated instrumentation that only knowledgeable and experienced individuals can calibrate, operate, and maintain. The BI may be employed also in monitoring routine runs.
As is indicated elsewhere in this chapter, the BI may be employed in a fraction negative mode to establish the ultimate microbiological survivor probability in designing an ethylene oxide sterilization cycle using inoculated product or inoculated simulated product.
使用环氧乙烷气体灭菌程序的条件通过使用前面讨论的方法得到完成。

不过，相对于其他灭菌程序该方法更加广泛，因为在除了温度，湿度，真空/正压力，环氧乙烷的浓度需要更加严格的控制。

一个重要的测定是要说明，在灭菌空间内的所有关键的工艺参数在整个时间中都是恰当的。

由于应用到物品灭菌的参数是至关重要的变数，预准备装载量，到达所需的水分含量以减少在装载环氧乙烷灭菌容器布置之前到达必需温度的保留时间是经常的可取的。

The validation process is generally made employing product inoculated with appropriate (BIs) such as spore preparations of Bacillus subtilis.确认程序通常被用于灌输有适当(BIs的)产品，例如枯草芽孢杆菌的孢子的准备。

为了确认，用于装满产品或模拟产品锅室。

湿度和气体浓度的检测需要利用精密仪表，只有知识渊博、经验丰富的人才能够校准、操作和维护。

Bl也可以用于常规流程的检测。

正如在本文所指出，Bl可用于一个小的阴性模式，以确定在通过的预防注射产物或者模拟产物得方法设置好的环氧乙烷程序中的最终的微生物存活概率。

One of the principal limitations of the ethylene oxide sterilization process is the limited ability of the gas to diffuse to the innermost product areas that require sterilization. Package design and chamber loading patterns therefore must be determined so that there is minimal resistance to gas diffusion.
环氧乙烷的最重要的局限之一是气体扩散到需要灭菌的产品最里面的能力是有限的。

因此必需决定包装设计和锅室装载模式从而对于气体扩散产生最小的阻力。

Sterilization by Ionizing Radiation
电离辐射灭菌法
The rapid proliferation of medical devices unable to withstand heat sterilization and the concerns about the safety of ethylene oxide have resulted in increasing applications of radiation sterilization. It is applicable also to drug substances and final dosage forms. The advantages of sterilization by irradiation include low chemical reactivity, low measurable residues, and the fact that there are fewer variables to control. In fact, radiation sterilization is
unique in that the basis of control is essentially that of the absorbed radiation dose, which can be precisely measured. Because of this characteristic, new procedures have been developed to determine the sterilizing dose. These, however, are still under review and appraisal, particularly with regard to the need, or otherwise, for additional controls and safety measures. Irradiation causes only a minimal temperature rise but can affect certain grades and types of plastics and glass.不能抗热力灭菌医疗用具的快速增加，还有环氧乙烷的安全性问题，使得辐射灭菌得到越来越多的应用。

这种方法同样适合药品和最终剂型。

辐射灭菌的优点包括：化学反应少、可测的残渣少和控制的变量少。

事实上，辐射消毒之所以出众，是因为它的基础是控制辐射吸收剂量，而辐射吸收剂量能被精确测量。

因为有此特征，已有新的程序已经发展来确定灭菌剂量。

然而，这些只是还处于回忆和评价阶段，特别是在关于需求或者额外控制和安全措施方面。

辐射只会导致温度稍微升高，不过能够对一定级别和类型的塑料和玻璃产生影响。

The two types of ionizing radiation in use are radioisotope decay (gamma radiation) and electron-beam radiation. In either case the radiation dose established to yield the required degree of sterility assurance should be such that, within the range of minimum and maximum doses set, the properties of the article being sterilized are acceptable.目前使用的两种电离辐射是放射性
同位素衰变〔γ辐射〕和电子束辐射。

无论使用哪种方法，都要求保证一定的无菌度，只要无菌度在最低限量和最高限量之间，结果就可接受。

For gamma irradiation, the validation of a procedure includes the establishment of article materials compatibility, establishment of product loading pattern and completion of dose mapping in the sterilization container (including identification of the minimum and maximum dose zones), establishment of timer setting, and demonstration of the delivery of the required sterilization dose. For electron-beam irradiation, in addition, the on-line control of voltage, current, conveyor speed, and electron beam scan dimension must be validated.于γ辐射，程序确实认包括物品材料相容性的制
定、产物装填模式的制定和完成在灭菌器中剂量的测绘制定〔包括最小和最大剂型带的鉴定〕、时间的制定和对呈递必需的灭菌剂量的证实。

此外，对于电子束辐射，必须确认电压即时控制、电流、输送速度和电子束扫描维度。

For gamma radiation sterilization, an effective sterilizing dose that is tolerated without damaging effect should be selected. 对于γ辐射灭菌，灭菌的有效剂量是在没有破坏作用时才被允许选择。

Although 2.5 megarads (Mrad) of absorbed radiation was historically selected, it is desirable and acceptable in some cases to employ lower doses for devices, drug substances, and finished dosage forms.虽然2.5 兆拉德〔 mrad 〕吸收的辐射是先前被选定的，它在某些情况下是可取的和可接受的，对设备，药物和成品剂型，运用较低剂量。

In other cases, however, higher doses are essential.在其他情况下，高剂量也是至关重要的。

In order to validate the efficacy particularly of the lower exposure levels, it is necessary to determine the magnitude (number, degree, or both) of the natural radiation resistance of the microbial population of the product. 在为了验证显著的疗效，尤其是低曝光水平，确定产品的微生物群体的自然辐射抗性大小〔数量，程度，或两者〕是有必要的。

Specific product loading patterns must be established, and absorbed minimum and maximum dosage distribution must be determined by use of chemical dosimeters.必须建立特定产品的装载模式和由化学放射剂量探测器确定吸收的最低和最高剂量分布。

(These dosimeters are usually dyed plastic cylinders, slides, or squares that show color intensification based directly on the amount of absorbed radiation energy; they require careful calibration.)〔这些放射量测定器通常是染色的塑料圆筒，斜体，或正方形显示颜色的明暗程度，基于直接吸收辐射能量的数量，它们需要仔细校准〕。

The setting of the preferred absorbed dose has been carried out on the basis of pure cultures of resistant microorganisms and employing inoculated product, e.g., with spores of Bacillus pumilus as biological indicators.在抗性的微生物和。