stored and distributed in a manner which prevents microbial growth, for example by constant
circulation at a temperature above 70°C.
59.水處理廠與分配系統的設計,建造與維護應當確保可靠供應恰當質量的水。系
統的運行不可以超過設計的能力。注射用水的生產,儲存和輸送,應當以防止微
生物的生長的方式進行,例如在70°C以上持續循環。
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. 所有設備如滅菌器,空氣處理和過濾系統,排風和氣體過濾,水處理,生產,儲存和
輸送系統都應當經過驗證和有計劃地維護;其重新使用應當經過批準。
Sanitation衛生
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.
潔凈區的衛生特別重要。要按照書面程序進行徹底清潔。如果需要消毒,應當
用一種以上的消毒劑。應當定期進行監測,以檢查耐藥菌的生長。
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.應當對清潔劑和消毒劑進行微生物污染監測;稀釋溶液應當保存在預先清潔過
的容器內,除非進行滅菌,只能保存規定的期限。A/B區使用的清潔劑和消毒劑
在使用前應該是無菌的。
63. Fumigation of clean areas may be useful for reducing microbiological contamination in
inaccessible places.
63.對潔凈區內難以進入的地方進行熏蒸是減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.
在所有加工階段,包括滅菌前各階段,應當注意采取措施預防使污染**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.
微生物制品不應當在其它藥品加工使用的區域進行制作或灌裝;但是死的微生
物或細菌提取物的疫苗在滅活后可以在其它無菌產品生產的設施中進行灌裝。
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.無菌過程的驗證應當包括利用營養培養基進行的一個過程模擬試驗(培養基灌
裝)。應當根據產品的劑型與培養基的選擇性,澄明度,濃度和滅菌的適應性來
選擇使用培養基。
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.模擬分裝試驗應當盡可能地接近日常的無菌制造工藝,包括關鍵的后續制造步
驟。同時要考慮在正常生產過程中的各種干擾,就如同**壞狀況。
 
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.模擬分裝試驗要作為**初的驗證來進行,要每個班次連續做三次滿意的模擬試驗,
并在規定的時間間隔或空氣處理系統,設備,生產方法和班次的任何重要改變
后,重復進行。通常每班和每個工藝每年應當重復進行兩次模擬分裝試驗。
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.模擬分裝試驗中用于培養基灌裝的容器的數量要足夠進行有效的評估。對一個小批量,
用于培養基灌裝的容器數量**少等于產品的批量。目標是零生長,以及隨后應用:
 
• When filling fewer than 5000 units, no contaminated units should be detected.
         灌封數低于5000時,不得檢出污染。
• When filling 5,000 to 10,000 units: 灌封數在5000**10000時:
a)  One (1) contaminated unit should result in an investigation, including#p#分頁標題#e#
consideration of a repeat media fill;
a)當有1單位被污染時,需進行調查,并應考慮重復培養基灌封試驗;
b)  Two (2) contaminated units are considered cause for revalidation, following
investigation.
b)當有2單位被污染時,需進行調查,并在調查后應進行再驗證。
• When filling more than 10,000 units: 灌封數超過10000時:
a)  One (1) contaminated unit should result in an investigation;
a)當有1單位被污染時,需進行調查;
b)  Two (2) contaminated units are considered cause for revalidation, following
investigation.  
b)當有2單位被污染時,需進行調查,并應在調查后進行再驗證。
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.對于任何大小的運行,斷斷續續的微生物污染事件可能指示著低水平的污染,應
當對這些污染進行調查。對較大的失敗進行的調查,調查應包括對從上一次模擬灌裝試驗合格后
所制造產品的潛在的無菌保證影響。
71. Care should be taken that any validation does not compromise the processes.
71.應當小心,任何驗證都不會影響工藝。
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,水處理設備與處理過的水,應當定期監測化學和微生物污染,在可能的情
況下,包括內毒素。對監測結果和采取的任何措施都應當保存記錄。
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. 在潔凈區內,特別是當無菌操作進行中,活動應當**少,并且人員的活動要受到
控制并按照方法,避免由于過多活動使塵埃顆粒脫落與微生物過度生長。因為
穿著工作服的性質,周圍環境的溫度和濕度不應當高到不舒服。
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應當**小。當表明該項目需要監控時,規格標準應當包
括微生物方面的質量要求。
75. Containers and materials liable to generate fibres should be minimised in clean areas.
75.容易產生纖維的容器與物料應當**小限度的出現在潔凈區。
76. Where appropriate, measures should be taken to minimize the particulate contamination of
the end product.
76.如果可能,應采取措施,使對終產品的塵埃粒子的污染**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,容器與設備進行清潔應當處理過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,容器與設備清洗和干燥以及滅菌之間的間隔時間,滅菌和使用之間的間隔
時間,應當**短并且在一定的儲存條件下應有時間限度。
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.溶液開始準備到滅菌或微孔過濾處理的時間間隔應當盡可能短。應該根據產
品的組分和規定的儲存方法,設定**長允許時間。
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.應監控滅菌前產品的微生物污染水平并確立控制標準,此標準與所采用滅菌方
法的功效相關。無論是無菌灌裝產品還是**終滅菌產品,均應進行滅菌前微生
物污染水平的檢查。采用過度殺滅程序的**終滅菌產品,滅菌前微生物污染水
平的檢查也許可定期進行。對實施參數放行的產品而言,應將此試驗視作中間
控制并須每批檢查。必要時,還應監控熱原的污染水平。可能情況下,應在緊挨#p#分頁標題#e#
灌裝點的位置,用除菌過濾器將所有藥液,尤其是大容量注射劑進行除菌過濾。
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,容器與設備以及其它無菌操作的潔凈區內需要的物品,應該滅菌并且通過
穿墻安裝的兩端開門的滅菌柜,或通過能夠達到同樣目的但不帶進污染的程序。
非易燃氣體要通過微生物過濾器。
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.應當驗證任何一個新程序的有效性,要根據運行歷史定期地再驗證核實,或當生產工藝或設
備有重大改變時,對驗證的結果進行再核實。
Sterilisation滅菌
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.應當對所有滅菌過程都進行驗證。特別要注意現行歐洲藥典沒有收載的滅菌
方法,或當所滅菌的產品不是簡單的水溶液或油狀溶液。可能的情況下,加熱
滅菌是一種可以選擇的方法。任何情況下,滅菌方法必須與上市及制造許可規
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.在采用任何一種滅菌方法前,該方法對產品的適應性,以及該方法對滅菌產品的各種裝
載情況的每一個部分達到期望的滅菌狀態的有效性,應當用實際的測量
或生物指示劑的方法進行證明。應當定期驗證該過程的有效性,**少每年一次,并
且在設備進行重大改變時要驗證確認。應當對驗證結果進行記錄。
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.對于滅菌有效性,所有物料必須按照要求進行處理,工藝設計應能保證滅菌的有效性。
86. Validated loading patterns should be established for all sterilisation processes.
86. 應當為所有滅菌工藝建立經過驗證的裝載方式。
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.應當考慮將生物指示劑作為滅菌輔助監測手段。生物指示劑應當按其制造企
業的說明進行儲存和使用,并利用陽性控制核實其質量。如果采用了生物指示
劑,應當采取嚴格的措施,防止由此所帶來的微生物污染。
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.應當清楚的方法區分滅菌的和沒有經過滅菌的產品。每一籃子,托盤或其它容
器裝的產品或部件應當清楚標識物料名稱,批號以及是否滅菌。在適當的地方,
可能使用滅菌指示劑如高壓滅菌帶,來表明一批(或亞批)產品是否經過滅菌處
理,但是,在實際上,它們不能可靠的指示該批產品無菌。
89. Sterilisation records should be available for each sterilisation run. They should be
approved as part of the batch release procedure.
89.每一次滅菌都應當有滅菌記錄,并作為批產品放行程序的一部分進行批準。
Sterilisation by heat加熱滅菌
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.、每一個加熱滅菌循環都應當在有足夠大刻度范圍的時間/溫度表上,或在其它有適#p#分頁標題#e#
當精確度的設備上記錄。用于控制,和/或,記錄的溫度探針的位置應當在驗證
時予以確定,如果可能,要用另一個溫度探針放在同一個位置進行核對。
91. Chemical or biological indicators may also be used, but should not take the place of
physical measurements.
91.化學或微生物指示劑可以使用,但不能代替物理檢測。
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.在開始測定滅菌時間前,必須有足夠的時間讓所有裝載的產品達到規定的溫
度。必須對每種裝載都確定這個時間。
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.在加熱滅菌的高溫階段后,應當在冷卻階段采取措施防止污染。任何與產品
接觸的冷卻劑或氣體都應當進行滅菌,除非證明不使用任何有泄露的容器。
Moist heat濕熱滅菌
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.應當同時使用溫度和壓力來監測滅菌過程。控制儀器與監測儀器和記錄表應當各
自獨立的。如果采用自動化的控制和監測系統,其應當經過驗證,保證達到關
鍵工藝要求。系統的和周期性的故障應當通過系統進行記錄和由操作者進行
觀察。應當對照滅菌過程中的記錄圖紙,對獨立的溫度指示器的讀取進行定
期檢查。在底部有排水裝置的滅菌器,在整個滅菌過程中也要記錄這個位置
的溫度。如果滅菌循環中有真空階段,應當經常進行泄露檢查。
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.如果滅菌的產品不是在密封的容器里,應當用能夠排除空氣并讓蒸汽滲入但
能夠防止滅菌后再污染的材料進行包裝。所有的裝載的產品,都應當與滅菌
劑在規定的溫度下接觸達到規定的時間。
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.、應當注意保證滅菌所用蒸汽質量,保證其包含物不會污染產品或設備。
 
 
Dry heat干法滅菌
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.該工藝應當包括在滅菌柜內的空氣循環和保持正壓以防止未滅菌空氣的進
入。所有進入的空氣應當通過HEPA過濾器。如果該工藝也用于除去熱源。
用內毒素進行挑戰性實驗應當作為該工藝驗證的一部分。
Sterilisation by radiation輻照滅菌
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.輻照滅菌主要用于熱敏感的物料或產品的滅菌。很多藥品和包裝材料是放射
敏感的,因此只有經過試驗證明不對產品產生有害結果時,才采用這種方法。
紫外輻照方法通常不作為可接受的滅菌方法。
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.在滅菌過程中,放射劑量應當進行測定。因此,應當用獨立于劑量率的放射量
測定指示器,對產品接受的劑量進行定量測量。應當足夠數量的劑量計插入#p#分頁標題#e#
產品中并保持足夠近的距離,以保證總有一個劑量計在照射器內。當使用塑
料的劑量計時,應當確保在它們的校驗期內。劑量計的吸光度應當在其暴露
在放射中很短一段時間后讀取。
100. Biological indicators may be used as an additional control
100.可以用微生物指示劑作為輔助控制。
101. Validation procedures should ensure that the effects of variations in density of the
packages are considered.
101.驗證過程應當保證所考慮到產品包裝的密度不同的影響。
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.物料處理程序應當防止輻照過與沒有輻照過的物料混淆。在每個包裝上應當
使用輻照敏感的色片,來區分已經輻照過的和未輻照的物料。
103. The total radiation dose should be administered within a predetermined time span.
103.應當在預先規定的時間范圍內完成總的輻照劑量。
Sterilisation with ethylene oxide環氧乙烷滅菌
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.這種方法應當只是在沒有其它合適方法的情況下使用。在工藝驗證過程中,
應當表明對產品沒有破壞作用,允許脫氣的條件和時間能夠將任何殘留氣體
和反應產物降低到該類產品或材料規定的可接受標準。
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.氣體和微生物細胞的直接接觸是關鍵;應當注意避免包裹在諸如晶體或干的
蛋白質內的生物體。包裝材料的性質和數量嚴重影響此工藝的效果。
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.在暴露氣體前,物料應當要達到工藝要求的溫度和濕度的平衡。需要的時間
應當同相反的需要平衡,從而使滅菌前時間**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.每一次的滅菌循環都應當用合適的微生物指示劑進行監測,將合適數量的指
示劑分布在滅菌裝載中。利用指示劑得到的信息應當作為產品批生產記錄的
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.每一個滅菌循環的記錄應當包括完成滅菌循環的時間,在滅菌過程中滅菌器
內部的壓力,溫度,濕度,以及氣體的濃度和總的用量。整個循環的溫度和壓力
應當記錄在圖紙上。記錄應當作為批記錄的一部分。
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.滅菌后,產品應當保存在經過驗證的控制狀態下,保持通風條件,使殘留氣體和
反應產物降低到規定的水平。此過程應當進行驗證。
Filtration of medicinal products which cannot be sterilised in their
final container不能在**終容器內進行滅菌的產品的過濾
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.當滅菌能在**終容器內進行的時候,只進行過濾是不充分的。就目前可用的
方法,蒸汽滅菌是較好的。如果產品不能在**終容器中進行滅菌,溶液或液體
可以用孔徑為0.22微米(或更小)的無菌過濾器,或有相當的微生物滯留能力
的過濾器,過濾到預先滅菌的容器中。這樣的過濾器可以除去大部分的細菌
和霉菌,但對病毒和支原體不能全部除去。應該考慮采取帶有一定程度熱處
理的過濾方法。
 
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#分頁標題#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.由于過濾方法與其它滅菌方法相比較有潛在的額外風險,可能建議在灌裝前
用另一個無菌的微生物滯留過濾器進行第二次除菌過濾。終端無菌過濾應當
盡可能靠近灌裝處。
112. Fibre-shedding characteristics of filters should be minimal.
112.過濾器應當盡可能不脫落纖維。
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.應該在使用前檢查除菌過濾器的完整性,并且在使用后應當立即用適當的方
法,如氣泡點,氣散流,或壓力保持試驗等方法進行測試確認。過濾一定量溶液
所用的時間和過濾器兩側的壓差應當在驗證時確定,在正常生產時任何明顯
的偏差都應當記錄和進行調查。這些檢查的結果應當包括在批記錄內。關鍵
氣體和空氣的過濾器的完整性應當在使用后進行檢查,其它的過濾器的完整性要在適當
的時間間隔內進行檢查。
114. The same filter should not be used for more than one working day unless such use has
been validated.
114.同一個過濾器使用不應當超過一個工作日,除非有驗證支持。
115. The filter should not affect the product by removal of ingredients from it or by release of
substances into it.
115.過濾器不應因為除去產品中成分或向產品中釋放某些物質而影響產品質量。
Finishing of sterile products無菌產品的完成
116. Partially stoppered freeze drying vials should be maintained under Grade A conditions at
all times until the stopper is fully inserted.
116.部分蓋好蓋的冷凍干燥瓶應當所有時間都保持在A級條件下,直到蓋完全蓋上。
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.容器的密封應采用經驗證的方法。熔封性容器,如玻璃或塑料安瓿,應進行
100%的完好性檢查。應根據適當的方法對其它容器的樣品進行密封完好性
檢查。
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.無菌灌裝的小瓶在完成鋁蓋軋到瓶蓋前,尚沒形成完整的密封系統。因此,壓
蓋應盡快在加蓋后完成。
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.由于小瓶的軋蓋會產生大量的非活性微粒,因此,軋蓋機應有隔離房間并有適
當的排風。
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.壓蓋可能作為一個無菌過程或在無菌核心之外的一個清潔過
程。當采用后一種方法,瓶應當在A條件級保護下直到離開無菌加工區域,因此
加塞的瓶應當在A級空氣的保護下,直到蓋帽軋好。
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.在壓蓋前應當挑出缺塞或掉塞的瓶。壓蓋區需要人工參與,應當使
用恰當的技術來防止人與瓶的直接接觸并使微生物污染的風險**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.限制進入的壁壘與隔離器可能對保證所需要的條件以及減少人工直接干涉
加蓋操作十分有益。
123. Containers sealed under vacuum should be tested for maintenance of that vacuum after
an appropriate, pre-determined period.
123.在真空條件下密封的容器,應該在適當的預先確定的日期后檢查真空保持度。
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#分頁標題#e#
should be validated and the performance of the equipment checked at intervals. Results
should be recorded.
124.灌裝了的注射劑的容器,要逐個檢查有無異物污染或其它缺陷。如果用目視
檢查,要在有合適的照明與背景下進行。進行目視檢查的操作人員
要定期通過視力檢查,可以佩戴眼鏡,并定期休息。采用其他檢
查方式時,應當進行方法驗證,并對設備的性能進行定期檢查,記錄檢查結果。
Quality control質量控制
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.對**終產品的無菌檢查僅是一系列無菌保證控制措施的**后一步。對產品有
關的檢查方法應進行驗證。
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.當授權進行參數放行時,應當特別注意對整個制造過程的驗證和監測。
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.無菌檢驗所取的樣品應當代表整個批的產品,但特別應該包括從
污染風險**大的部分中所取的樣品,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.對無菌灌裝的產品,樣品應包括容器灌裝批的開始,結束以及中間任何
重要調整之后的樣品,
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.或對在**終容器中進行加熱滅菌的產品,應該考慮從裝載的**低溫度
的地方取樣。