欧盟GMP关于无菌室要求

 
 
stored and distributed in a manner which prevents microbial growth, for example by constant
circulation at a temperature above 70°C.
59.水处理厂与分配系统的设计,建造与维护应当确保可靠供应恰当质量的水。系
统的运行不可以超过设计的能力。注射用水的生产,储存和输送,应当以防止微
生物的生长的方式进行,例如在70°C以上持续循环。
60. All equipment such as sterilisers, air handling and filtration systems, air vent and gas
filters, water treatment, generation, storage and distribution systems should be subject to
validation and planned maintenance; their return to use should be approved.
60. 所有设备如灭菌器,空气处理和过滤系统,排风和气体过滤,水处理,生产,储存和
输送系统都应当经过验证和有计划地维护;其重新使用应当经过批准。
Sanitation卫生
61. The sanitation of clean areas is particularly important. They should be cleaned thoroughly
in accordance with a written programme. Where disinfectants are used, more than one type
should be employed. Monitoring should be undertaken regularly in order to detect the
development of resistant strains.
洁净区的卫生特别重要。要按照书面程序进行彻底清洁。如果需要消毒,应当
用一种以上的消毒剂。应当定期进行监测,以检查耐药菌的生长。
62. Disinfectants and detergents should be monitored for microbial contamination; dilutions
should be kept in previously cleaned containers and should only be stored for defined periods
unless sterilised. Disinfectants and detergents used in Grades A and B areas should be sterile
prior to use.
62.应当对清洁剂和消毒剂进行微生物污染监测;稀释溶液应当保存在预先清洁过
的容器内,除非进行灭菌,只能保存规定的期限。A/B区使用的清洁剂和消毒剂
在使用前应该是无菌的。
63. Fumigation of clean areas may be useful for reducing microbiological contamination in
inaccessible places.
63.对洁净区内难以进入的地方进行熏蒸是减少微生物污染的有用的方法。
Processing加工
64. Precautions to minimize contamination should be taken during all processing stages
including the stages before sterilisation.
在所有加工阶段,包括灭菌前各阶段,应当注意采取措施预防使污染**小。
65. Preparations of microbiological origin should not be made or filled in areas used for the
processing of other medicinal products; however, vaccines of dead organisms or of bacterial
extracts may be filled, after inactivation, in the same premises as other sterile medicinal
products.
微生物制品不应当在其它药品加工使用的区域进行制作或灌装;但是死的微生
物或细菌提取物的疫苗在灭活后可以在其它无菌产品生产的设施中进行灌装。
66. Validation of aseptic processing should include a process simulation test using a nutrient
medium (media fill).Selection of the nutrient medium should be made based on dosage form
of the product and selectivity, clarity, concentration and suitability for sterilisation of the
nutrient medium.
66.无菌过程的验证应当包括利用营养培养基进行的一个过程模拟试验(培养基灌
装)。应当根据产品的剂型与培养基的选择性,澄明度,浓度和灭菌的适应性来
选择使用培养基。
67. The process simulation test should imitate as closely as possible the routine aseptic
manufacturing process and include all the critical subsequent manufacturing steps. It should
also take into account various interventions known to occur during normal production as well
as worst-case situations.
67.模拟分装试验应当尽可能地接近日常的无菌制造工艺,包括关键的后续制造步
骤。同时要考虑在正常生产过程中的各种干扰,就如同**坏状况。
 
68. Process simulation tests should be performed as initial validation with three consecutive
satisfactory simulation tests per shift and repeated at defined intervals and after any
significant modification to the HVAC-system, equipment, process and number of shifts.
Normally process simulation tests should be repeated twice a year per shift and process.
68.模拟分装试验要作为**初的验证来进行,要每个班次连续做三次满意的模拟试验,
并在规定的时间间隔或空气处理系统,设备,生产方法和班次的任何重要改变
后,重复进行。通常每班和每个工艺每年应当重复进行两次模拟分装试验。
69. The number of containers used for media fills should be sufficient to enable a valid
evaluation. For small batches, the number of containers for media fills should at least equal
the size of the product batch. The target should be zero growth and the following should
apply:  
69.模拟分装试验中用于培养基灌装的容器的数量要足够进行有效的评估。对一个小批量,
用于培养基灌装的容器数量**少等于产品的批量。目标是零生长,以及随后应用:
 
• When filling fewer than 5000 units, no contaminated units should be detected.
         灌封数低于5000时,不得检出污染。
• When filling 5,000 to 10,000 units: 灌封数在5000**10000时:
a)  One (1) contaminated unit should result in an investigation, including#p#分页标题#e#
consideration of a repeat media fill;
a)当有1单位被污染时,需进行调查,并应考虑重复培养基灌封试验;
b)  Two (2) contaminated units are considered cause for revalidation, following
investigation.
b)当有2单位被污染时,需进行调查,并在调查后应进行再验证。
• When filling more than 10,000 units: 灌封数超过10000时:
a)  One (1) contaminated unit should result in an investigation;
a)当有1单位被污染时,需进行调查;
b)  Two (2) contaminated units are considered cause for revalidation, following
investigation.  
b)当有2单位被污染时,需进行调查,并应在调查后进行再验证。
70. For any run size, intermittent incidents of microbial contamination may be indicative of
low-level contamination that should be investigated. Investigation of gross failures should
include the potential impact on the sterility assurance of batches manufactured since the last
successful media fill.  
70.对于任何大小的运行,断断续续的微生物污染事件可能指示着低水平的污染,应
当对这些污染进行调查。对较大的失败进行的调查,调查应包括对从上一次模拟灌装试验合格后
所制造产品的潜在的无菌保证影响。
71. Care should be taken that any validation does not compromise the processes.
71.应当小心,任何验证都不会影响工艺。
72. Water sources, water treatment equipment and treated water should be monitored
regularly for chemical and biological contamination and, as appropriate, for endotoxins.
Records should be maintained of the results of the monitoring and of any action taken.
72. 水源,水处理设备与处理过的水,应当定期监测化学和微生物污染,在可能的情
况下,包括内毒素。对监测结果和采取的任何措施都应当保存记录。
73. Activities in clean areas and especially when aseptic operations are in progress should be
kept to a minimum and movement of personnel should be controlled and methodical, to avoid
excessive shedding of particles and organisms due to over-vigorous activity. The ambient
temperature and humidity should not be uncomfortably high because of the nature of the
garments worn.
73. 在洁净区内,特别是当无菌操作进行中,活动应当**少,并且人员的活动要受到
控制并按照方法,避免由于过多活动使尘埃颗粒脱落与微生物过度生长。因为
穿着工作服的性质,周围环境的温度和湿度不应当高到不舒服。
74. Microbiological contamination of starting materials should be minimal. Specifications
should include requirements for microbiological quality when the need for this has been
indicated by monitoring.
74.起始物料的微生物污染应当**小。当表明该项目需要监控时,规格标准应当包
括微生物方面的质量要求。
75. Containers and materials liable to generate fibres should be minimised in clean areas.
75.容易产生纤维的容器与物料应当**小限度的出现在洁净区。
76. Where appropriate, measures should be taken to minimize the particulate contamination of
the end product.
76.如果可能,应采取措施,使对终产品的尘埃粒子的污染**小。
77. Components, containers and equipment should be handled after the final cleaning process
in such a way that they are not recontaminated.
77.部件,容器与设备进行清洁应当处理过程中要避免再次污染。
78. The interval between the washing and drying and the sterilisation of components,
containers and equipment as well as between their sterilisation and use should be minimised
and subject to a time-limit appropriate to the storage conditions.
78.部件,容器与设备清洗和干燥以及灭菌之间的间隔时间,灭菌和使用之间的间隔
时间,应当**短并且在一定的储存条件下应有时间限度。
79. The time between the start of the preparation of a solution and its sterilisation or filtration
through a micro-organism-retaining filter should be minimised. There should be a set
maximum permissible time for each product that takes into account its composition and the
prescribed method of storage.
79.溶液开始准备到灭菌或微孔过滤处理的时间间隔应当尽可能短。应该根据产
品的组分和规定的储存方法,设定**长允许时间。
80. The bioburden should be monitored before sterilisation. There should be working limits
on contamination immediately before sterilisation, which are related to the efficiency of the
method to be used. Bioburden assay should be performed on each batch for both aseptically
filled product and terminally sterilised products. Where overkill sterilisation parameters are
set for terminally sterilised products, bioburden might be monitored only at suitable scheduled
intervals. For parametric release systems, bioburden assay should be performed on each batch
and considered as an in-process test. Where appropriate the level of endotoxins should be
monitored. All solutions, in particular large volume infusion fluids, should be passed through
a micro-organism-retaining filter, if possible sited immediately before filling.  
80.应监控灭菌前产品的微生物污染水平并确立控制标准,此标准与所采用灭菌方
法的功效相关。无论是无菌灌装产品还是**终灭菌产品,均应进行灭菌前微生
物污染水平的检查。采用过度杀灭程序的**终灭菌产品,灭菌前微生物污染水
平的检查也许可定期进行。对实施参数放行的产品而言,应将此试验视作中间
控制并须每批检查。必要时,还应监控热原的污染水平。可能情况下,应在紧挨#p#分页标题#e#
灌装点的位置,用除菌过滤器将所有药液,尤其是大容量注射剂进行除菌过滤。
81. Components, containers, equipment and any other article required in a clean area where
aseptic work takes place should be sterilised and passed into the area through double-ended
sterilisers sealed into the wall, or by a procedure which achieves the same objective of not
introducing contamination. Non-combustible gases should be passed through micro-organism
retentive filters.
81.部件,容器与设备以及其它无菌操作的洁净区内需要的物品,应该灭菌并且通过
穿墙安装的两端开门的灭菌柜,或通过能够达到同样目的但不带进污染的程序。
非易燃气体要通过微生物过滤器。
82. The efficacy of any new procedure should be validated, and the validation verified at
scheduled intervals based on performance history or when any significant change is made in
the process or equipment.
82.应当验证任何一个新程序的有效性,要根据运行历史定期地再验证核实,或当生产工艺或设
备有重大改变时,对验证的结果进行再核实。
Sterilisation灭菌
83. All sterilisation processes should be validated. Particular attention should be given when
the adopted sterilisation method is not described in the current edition of the European
Pharmacopoeia, or when it is used for a product which is not a simple aqueous or oily
solution. Where possible, heat sterilisation is the method of choice. In any case, the
sterilisation process must be in accordance with the marketing and manufacturing
authorisations.
83.应当对所有灭菌过程都进行验证。特别要注意现行欧洲药典没有收载的灭菌
方法,或当所灭菌的产品不是简单的水溶液或油状溶液。可能的情况下,加热
灭菌是一种可以选择的方法。任何情况下,灭菌方法必须与上市及制造许可规
定的方法一致。
84. Before any sterilisation process is adopted its suitability for the product and its efficacy in
achieving the desired sterilising conditions in all parts of each type of load to be processed
should be demonstrated by physical measurements and by biological indicators where
appropriate. The validity of the process should be verified at scheduled intervals, at least
annually, and whenever significant modifications have been made to the equipment. Records
should be kept of the results.
84.在采用任何一种灭菌方法前,该方法对产品的适应性,以及该方法对灭菌产品的各种装
载情况的每一个部分达到期望的灭菌状态的有效性,应当用实际的测量
或生物指示剂的方法进行证明。应当定期验证该过程的有效性,**少每年一次,并
且在设备进行重大改变时要验证确认。应当对验证结果进行记录。
85. For effective sterilisation the whole of the material must be subjected to the required
treatment and the process should be designed to ensure that this is achieved.
85.对于灭菌有效性,所有物料必须按照要求进行处理,工艺设计应能保证灭菌的有效性。
86. Validated loading patterns should be established for all sterilisation processes.
86. 应当为所有灭菌工艺建立经过验证的装载方式。
87. Biological indicators should be considered as an additional method for monitoring the
sterilisation. They should be stored and used according to the manufacturer’s instructions, and
their quality checked by positive controls. If biological indicators are used, strict precautions
should be taken to avoid transferring microbial contamination from them.
87.应当考虑将生物指示剂作为灭菌辅助监测手段。生物指示剂应当按其制造企
业的说明进行储存和使用,并利用阳性控制核实其质量。如果采用了生物指示
剂,应当采取严格的措施,防止由此所带来的微生物污染。
88. There should be a clear means of differentiating products which have not been sterilised
from those which have. Each basket, tray or other carrier of products or components should
be clearly labelled with the material name, its batch number and an indication of whether or
not it has been sterilised. Indicators such as autoclave tape may be used, where appropriate, to
indicate whether or not a batch (or sub-batch) has passed through a sterilisation process, but
they do not give a reliable indication that the lot is, in fact, sterile.
88.应当清楚的方法区分灭菌的和没有经过灭菌的产品。每一篮子,托盘或其它容
器装的产品或部件应当清楚标识物料名称,批号以及是否灭菌。在适当的地方,
可能使用灭菌指示剂如高压灭菌带,来表明一批(或亚批)产品是否经过灭菌处
理,但是,在实际上,它们不能可靠的指示该批产品无菌。
89. Sterilisation records should be available for each sterilisation run. They should be
approved as part of the batch release procedure.
89.每一次灭菌都应当有灭菌记录,并作为批产品放行程序的一部分进行批准。
Sterilisation by heat加热灭菌
90. Each heat sterilisation cycle should be recorded on a time/temperature chart with a
sufficiently large scale or by other appropriate equipment with suitable accuracy and
precision. The position of the temperature probes used for controlling and/or recording should
have been determined during the validation, and where applicable also checked against a
second independent temperature probe located at the same position.
90.、每一个加热灭菌循环都应当在有足够大刻度范围的时间/温度表上,或在其它有适#p#分页标题#e#
当精确度的设备上记录。用于控制,和/或,记录的温度探针的位置应当在验证
时予以确定,如果可能,要用另一个温度探针放在同一个位置进行核对。
91. Chemical or biological indicators may also be used, but should not take the place of
physical measurements.
91.化学或微生物指示剂可以使用,但不能代替物理检测。
92. Sufficient time must be allowed for the whole of the load to reach the required
temperature before measurement of the sterilising time-period is commenced. This time must
be determined for each type of load to be processed.
92.在开始测定灭菌时间前,必须有足够的时间让所有装载的产品达到规定的温
度。必须对每种装载都确定这个时间。
93. After the high temperature phase of a heat sterilisation cycle, precautions should be taken
against contamination of a sterilised load during cooling. Any cooling fluid or gas in contact
with the product should be sterilised unless it can be shown that any leaking container would
not be approved for use.
93.在加热灭菌的高温阶段后,应当在冷却阶段采取措施防止污染。任何与产品
接触的冷却剂或气体都应当进行灭菌,除非证明不使用任何有泄露的容器。
Moist heat湿热灭菌
94. Both temperature and pressure should be used to monitor the process. Control
instrumentation should normally be independent of monitoring instrumentation and recording
charts. Where automated control and monitoring systems are used for these applications they
should be validated to ensure that critical process requirements are met. System and cycle
faults should be registered by the system and observed by the operator. The reading of the
independent temperature indicator should be routinely checked against the chart recorder
during the sterilisation period. For sterilisers fitted with a drain at the bottom of the chamber,
it may also be necessary to record the temperature at this position, throughout the sterilisation
period. There should be frequent leak tests on the chamber when a vacuum phase is part of the
cycle.
94.应当同时使用温度和压力来监测灭菌过程。控制仪器与监测仪器和记录表应当各
自独立的。如果采用自动化的控制和监测系统,其应当经过验证,保证达到关
键工艺要求。系统的和周期性的故障应当通过系统进行记录和由操作者进行
观察。应当对照灭菌过程中的记录图纸,对独立的温度指示器的读取进行定
期检查。在底部有排水装置的灭菌器,在整个灭菌过程中也要记录这个位置
的温度。如果灭菌循环中有真空阶段,应当经常进行泄露检查。
95. The items to be sterilised, other than products in sealed containers, should be wrapped in a
material which allows removal of air and penetration of steam but which prevents
recontamination after sterilisation. All parts of the load should be in contact with the
sterilizing agent at the required temperature for the required time.
95.如果灭菌的产品不是在密封的容器里,应当用能够排除空气并让蒸汽渗入但
能够防止灭菌后再污染的材料进行包装。所有的装载的产品,都应当与灭菌
剂在规定的温度下接触达到规定的时间。
96. Care should be taken to ensure that steam used for sterilisation is of suitable quality and
does not contain additives at a level which could cause contamination of product or
equipment.
96.、应当注意保证灭菌所用蒸汽质量,保证其包含物不会污染产品或设备。
 
 
Dry heat干法灭菌
97. The process used should include air circulation within the chamber and the maintenance
of a positive pressure to prevent the entry of non-sterile air. Any air admitted should be
passed through a HEPA filter. Where this process is also intended to remove pyrogens,
challenge tests using endotoxins should be used as part of the validation.
97.该工艺应当包括在灭菌柜内的空气循环和保持正压以防止未灭菌空气的进
入。所有进入的空气应当通过HEPA过滤器。如果该工艺也用于除去热源。
用内毒素进行挑战性实验应当作为该工艺验证的一部分。
Sterilisation by radiation辐照灭菌
98. Radiation sterilisation is used mainly for the sterilisation of heat sensitive materials and
products. Many medicinal products and some packaging materials are radiation-sensitive, so
this method is permissible only when the absence of deleterious effects on the product has
been confirmed experimentally. Ultraviolet irradiation is not normally an acceptable method
of sterilisation.
98.辐照灭菌主要用于热敏感的物料或产品的灭菌。很多药品和包装材料是放射
敏感的,因此只有经过试验证明不对产品产生有害结果时,才采用这种方法。
紫外辐照方法通常不作为可接受的灭菌方法。
99. During the sterilisation procedure the radiation dose should be measured. For this purpose,
dosimetry indicators which are independent of dose rate should be used, giving a quantitative
measurement of the dose received by the product itself. Dosimeters should be inserted in the
load in sufficient number and close enough together to ensure that there is always a dosimeter
in the irradiator. Where plastic dosimeters are used they should be used within the time-limit
of their calibration. Dosimeter absorbances should be read within a short period after
exposure to radiation.
99.在灭菌过程中,放射剂量应当进行测定。因此,应当用独立于剂量率的放射量
测定指示器,对产品接受的剂量进行定量测量。应当足够数量的剂量计插入#p#分页标题#e#
产品中并保持足够近的距离,以保证总有一个剂量计在照射器内。当使用塑
料的剂量计时,应当确保在它们的校验期内。剂量计的吸光度应当在其暴露
在放射中很短一段时间后读取。
100. Biological indicators may be used as an additional control
100.可以用微生物指示剂作为辅助控制。
101. Validation procedures should ensure that the effects of variations in density of the
packages are considered.
101.验证过程应当保证所考虑到产品包装的密度不同的影响。
102. Materials handling procedures should prevent mix-up between irradiated and non-
irradiated materials. Radiation sensitive colour disks should also be used on each package to
differentiate between packages which have been subjected to irradiation and those which have
not.
102.物料处理程序应当防止辐照过与没有辐照过的物料混淆。在每个包装上应当
使用辐照敏感的色片,来区分已经辐照过的和未辐照的物料。
103. The total radiation dose should be administered within a predetermined time span.
103.应当在预先规定的时间范围内完成总的辐照剂量。
Sterilisation with ethylene oxide环氧乙烷灭菌
104. This method should only be used when no other method is practicable. During process
validation it should be shown that there is no damaging effect on the product and that the
conditions and time allowed for degassing are such as to reduce any residual gas and reaction
products to defined acceptable limits for the type of product or material.
104.这种方法应当只是在没有其它合适方法的情况下使用。在工艺验证过程中,
应当表明对产品没有破坏作用,允许脱气的条件和时间能够将任何残留气体
和反应产物降低到该类产品或材料规定的可接受标准。
105. Direct contact between gas and microbial cells is essential; precautions should be taken
to avoid the presence of organisms likely to be enclosed in material such as crystals or dried
protein. The nature and quantity of packaging materials can significantly affect the process.
105.气体和微生物细胞的直接接触是关键;应当注意避免包裹在诸如晶体或干的
蛋白质内的生物体。包装材料的性质和数量严重影响此工艺的效果。
106. Before exposure to the gas, materials should be brought into equilibrium with the
humidity and temperature required by the process. The time required for this should be
balanced against the opposing need to minimize the time before sterilisation.
106.在暴露气体前,物料应当要达到工艺要求的温度和湿度的平衡。需要的时间
应当同相反的需要平衡,从而使灭菌前时间**小。
107. Each sterilisation cycle should be monitored with suitable biological indicators, using the
appropriate number of test pieces distributed throughout the load. The information so
obtained should form part of the batch record.
107.每一次的灭菌循环都应当用合适的微生物指示剂进行监测,将合适数量的指
示剂分布在灭菌装载中。利用指示剂得到的信息应当作为产品批生产记录的
一部分。
108. For each sterilisation cycle, records should be made of the time taken to complete the
cycle, of the pressure, temperature and humidity within the chamber during the process and of
the gas concentration and of the total amount of gas used. The pressure and temperature
should be recorded throughout the cycle on a chart. The record(s) should form part of the
batch record.
108.每一个灭菌循环的记录应当包括完成灭菌循环的时间,在灭菌过程中灭菌器
内部的压力,温度,湿度,以及气体的浓度和总的用量。整个循环的温度和压力
应当记录在图纸上。记录应当作为批记录的一部分。
109. After sterilisation, the load should be stored in a controlled manner under ventilated
conditions to allow residual gas and reaction products to reduce to the defined level. This
process should be validated.
109.灭菌后,产品应当保存在经过验证的控制状态下,保持通风条件,使残留气体和
反应产物降低到规定的水平。此过程应当进行验证。
Filtration of medicinal products which cannot be sterilised in their
final container不能在**终容器内进行灭菌的产品的过滤
110. Filtration alone is not considered sufficient when sterilisation in the final container is
possible. With regard to methods currently available, steam sterilisation is to be preferred. If
the product cannot be sterilised in the final container, solutions or liquids can be filtered
through a sterile filter of nominal pore size of 0.22 micron (or less), or with at least equivalent
micro-organism retaining properties, into a previously sterilised container. Such filters can
remove most bacteria and moulds, but not all viruses or mycoplasmas. Consideration should
be given to complementing the filtration process with some degree of heat treatment.
110.当灭菌能在**终容器内进行的时候,只进行过滤是不充分的。就目前可用的
方法,蒸汽灭菌是较好的。如果产品不能在**终容器中进行灭菌,溶液或液体
可以用孔径为0.22微米(或更小)的无菌过滤器,或有相当的微生物滞留能力
的过滤器,过滤到预先灭菌的容器中。这样的过滤器可以除去大部分的细菌
和霉菌,但对病毒和支原体不能全部除去。应该考虑采取带有一定程度热处
理的过滤方法。
 
111. Due to the potential additional risks of the filtration method as compared with other
sterilization processes, a second filtration via a further sterilised micro-organism retaining#p#分页标题#e#
filter, immediately prior to filling, may be advisable. The final sterile filtration should be
carried out as close as possible to the filling point.
111.由于过滤方法与其它灭菌方法相比较有潜在的额外风险,可能建议在灌装前
用另一个无菌的微生物滞留过滤器进行第二次除菌过滤。终端无菌过滤应当
尽可能靠近灌装处。
112. Fibre-shedding characteristics of filters should be minimal.
112.过滤器应当尽可能不脱落纤维。
113. The integrity of the sterilised filter should be verified before use and should be
confirmed immediately after use by an appropriate method such as a bubble point, diffusive
flow or pressure hold test. The time taken to filter a known volume of bulk solution and the
pressure difference to be used across the filter should be determined during validation and any
significant differences from this during routine manufacturing should be noted and
investigated. Results of these checks should be included in the batch record. The integrity of
critical gas and air vent filters should be confirmed after use. The integrity of other filters
should be confirmed at appropriate intervals.
113.应该在使用前检查除菌过滤器的完整性,并且在使用后应当立即用适当的方
法,如气泡点,气散流,或压力保持试验等方法进行测试确认。过滤一定量溶液
所用的时间和过滤器两侧的压差应当在验证时确定,在正常生产时任何明显
的偏差都应当记录和进行调查。这些检查的结果应当包括在批记录内。关键
气体和空气的过滤器的完整性应当在使用后进行检查,其它的过滤器的完整性要在适当
的时间间隔内进行检查。
114. The same filter should not be used for more than one working day unless such use has
been validated.
114.同一个过滤器使用不应当超过一个工作日,除非有验证支持。
115. The filter should not affect the product by removal of ingredients from it or by release of
substances into it.
115.过滤器不应因为除去产品中成分或向产品中释放某些物质而影响产品质量。
Finishing of sterile products无菌产品的完成
116. Partially stoppered freeze drying vials should be maintained under Grade A conditions at
all times until the stopper is fully inserted.
116.部分盖好盖的冷冻干燥瓶应当所有时间都保持在A级条件下,直到盖完全盖上。
117. Containers should be closed by appropriately validated methods. Containers closed by
fusion, e.g. glass or plastic ampoules should be subject to 100% integrity testing. Samples
of other containers should be checked for integrity according to appropriate procedures.  
117.容器的密封应采用经验证的方法。熔封性容器,如玻璃或塑料安瓿,应进行
100%的完好性检查。应根据适当的方法对其它容器的样品进行密封完好性
检查。
118. The container closure system for aseptically filled vials is not fully integral until the
aluminium cap has been crimped into place on the stoppered vial. Crimping of the cap should
therefore be performed as soon as possible after stopper insertion.  
118.无菌灌装的小瓶在完成铝盖轧到瓶盖前,尚没形成完整的密封系统。因此,压
盖应尽快在加盖后完成。
119. As the equipment used to crimp vial caps can generate large quantities of non-viable
particulates, the equipment should be located at a separate station equipped with adequate air
extraction.  
119.由于小瓶的轧盖会产生大量的非活性微粒,因此,轧盖机应有隔离房间并有适
当的排风。
120. Vial capping can be undertaken as an aseptic process using sterilised caps or as a clean
process outside the aseptic core. Where this latter approach is adopted, vials should beprotected by Grade A conditions up to the point of leaving the aseptic processing area, and thereafter stoppered vials should be protected with a Grade A air supply until the cap has been crimped.
120.压盖可能作为一个无菌过程或在无菌核心之外的一个清洁过
程。当采用后一种方法,瓶应当在A条件级保护下直到离开无菌加工区域,因此
加塞的瓶应当在A级空气的保护下,直到盖帽轧好。
121. Vials with missing or displaced stoppers should be rejected prior to capping. Where
human intervention is required at the capping station, appropriate technology should be used
to prevent direct contact with the vials and to minimise microbial contamination.  
121.在压盖前应当挑出缺塞或掉塞的瓶。压盖区需要人工参与,应当使
用恰当的技术来防止人与瓶的直接接触并使微生物污染的风险**小。
122. Restricted access barriers and isolators may be beneficial in assuring the required
conditions and minimising direct human interventions into the capping operation.
122.限制进入的壁垒与隔离器可能对保证所需要的条件以及减少人工直接干涉
加盖操作十分有益。
123. Containers sealed under vacuum should be tested for maintenance of that vacuum after
an appropriate, pre-determined period.
123.在真空条件下密封的容器,应该在适当的预先确定的日期后检查真空保持度。
124. Filled containers of parenteral products should be inspected individually for extraneous
contamination or other defects. When inspection is done visually, it should be done under
suitable and controlled conditions of illumination and background. Operators doing the
inspection should pass regular eye-sight checks, with spectacles if worn, and be allowed
frequent breaks from inspection. Where other methods of inspection are used, the process#p#分页标题#e#
should be validated and the performance of the equipment checked at intervals. Results
should be recorded.
124.灌装了的注射剂的容器,要逐个检查有无异物污染或其它缺陷。如果用目视
检查,要在有合适的照明与背景下进行。进行目视检查的操作人员
要定期通过视力检查,可以佩戴眼镜,并定期休息。采用其他检
查方式时,应当进行方法验证,并对设备的性能进行定期检查,记录检查结果。
Quality control质量控制
125. The sterility test applied to the finished product should only be regarded as the last in a
series of control measures by which sterility is assured. The test should be validated for the
product(s) concerned.
125.对**终产品的无菌检查仅是一系列无菌保证控制措施的**后一步。对产品有
关的检查方法应进行验证。
126. In those cases where parametric release has been authorised, special attention should be
paid to the validation and the monitoring of the entire manufacturing process.
126.当授权进行参数放行时,应当特别注意对整个制造过程的验证和监测。
127. Samples taken for sterility testing should be representative of the whole of the batch, but
should in particular include samples taken from parts of the batch considered to be most at
risk of contamination, e.g.:  
127.无菌检验所取的样品应当代表整个批的产品,但特别应该包括从
污染风险**大的部分中所取的样品,例如:
a. for products which have been filled aseptically, samples should include containers filled at
the beginning and end of the batch and after any significant intervention,
a.对无菌灌装的产品,样品应包括容器灌装批的开始,结束以及中间任何
重要调整之后的样品,
b. or products which have been heat sterilised in their final containers, consideration should
be given to taking samples from the potentially coolest part of the load.
 
b.或对在**终容器中进行加热灭菌的产品,应该考虑从装载的**低温度
的地方取样。