EU GMP ANNEX 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS （中英文对照）
(a) These are average values. （一）这些都是平均值。
(b) Individual settle plates may be exposed for less than 4 hours. （二）单个沉降皿放置的时间可以少于4小时。
20. Appropriate alert and action limits should be set for the results of particulate and microbiological monitoring. If these limits are exceeded operating procedures should prescribe corrective action。对尘埃粒子和微生物的监控结果，要设置适当的警戒限度和行动限度。当超出这些限度时，操作规程应说明需要采取的措施。
Isolator technology 隔离技术
21. The utilisation of isolator technology to minimize human interventions in processing areas may result in a significant decrease in the risk of microbiological contamination of aseptically manufactured products from the environment. There are many possible designs of isolators and transfer devices. The isolator and the background environment should be designed so that the required air quality for the respective zones can be realised. Isolators are constructed of various materials more or less prone to puncture and leakage. Transfer devices may vary from a single door to double door designs to fully sealed systems incorporating sterilization mechanisms. 在生产区采用人员方面的隔离技术，在无菌产品的生产中，会显著降低周围环境微生物污染的风险。有很多隔离和传递设施可供选择，隔离和背景环境的设计，必须保证各区域相应的空气质量要求。隔离设施的建造材料，多少有些易于穿孔和泄漏。传递设施可以是单门、双门或结合无菌机制的全封闭系统。
22. The transfer of materials into and out of the unit is one of the greatest potential sources of contamination. In general the area inside the 原材料的进出是污染的最大来源之一。尽管人们已经认可，层流罩不可能存在于所有隔离设施的工作区内，但是，通常隔离区内是
isolator is the local zone for high risk
manipulations, although it is recognised that
laminar air flow may not exist in the working zone
of all such devices.
高风险操作的局部区域。
23. The air classification required for the background environment depends on the design of the isolator and its application. It should be controlled and for aseptic processing it should be at least grade D. 背景环境的洁净级别，视隔离区的设计和应用而定。要控制无菌生产的背景环境，并且最低为D级
24. Isolators should be introduced only after appropriate validation. Validation should take into account all critical factors of isolator technology, for example the quality of the air inside and outside (background) the isolator, sanitisation of the isolator, the transfer process and isolator integrity. 在经过适当的验证之后，隔离器才能使用。验证必须将隔离技术的所有关键因素考虑在内，如：隔离器的内外部空气质量、隔离器的消毒，传递过程和隔离器的完整性。
25. Monitoring should be carried out routinely and should include frequent leak testing of the isolator and glove/sleeve system 必须进行常规监控，包括隔离室和手套/袖系统的泄漏检查。
Blow/fill/seal technologym. (26-27)吹/灌/封技术Terminally sterilised products (28-30) 最终灭菌产品Aseptic preparation 无菌制备
31. Components after washing should be handled in at least a grade D environment. Handling of sterile starting materials and components, unless subjected to sterilisation or filtration through a micro-organism-retaining filter later in the process, should be done in a grade A environment with grade B background.清洗后的材料要在最低D级环境下处理。无菌产品的原料和辅料，除非将在生产过程中进行灭菌或采用微生物滞留过滤器过滤除菌，要在B级环境下的A级区处理。
32. Preparation of solutions which are to be sterile filtered during the process should be done in a grade C environment; if not filtered, the preparation of materials and products should be done in a grade A environment with a grade B background.采用过滤除菌的溶液的制备，要在C级环境下进行，如果不过滤，要在B级环境下的A 级区处理。
33. Handling and filling of aseptically prepared products should be done in a grade A environment with a grade B background.通过无菌方法生产的产品，要在B级环境下的A级区处理和灌装。
34. Prior to the completion of stoppering, transfer of partially closed containers, as used in freeze 在完成加盖前，半密封容器的传递，如在冻干中使用的，要在B级环境下的A级区进行，
drying should be done either in a grade A
environment with grade B background or in sealed
transfer trays in a grade B environment.
或在B级环境中的密封的转移盘中进行。
35. Preparation and filling of sterile ointments, creams, suspensions and emulsions should be done in a grade A environment, with a grade B background, when the product is exposed and is not subsequently filtered. 如果产品有暴露和不再进行灭菌，软膏、霜剂、混悬剂、栓剂和乳剂的制备和灌装，要在B级环境下的A级区处理。
Personnel
36. Only the minimum number of personnel required should be present in clean areas; this is particularly important during aseptic processing. Inspections and controls should be conducted outside the clean areas as far as possible. 人员
只有工作需要的最低人数可以进入洁净区，这对无菌生产过程特别重要。检查和控制都要尽可能在洁净区外面进行。
37. All personnel (including those concerned with cleaning and maintenance) employed in such areas should receive regular training in disciplines relevant to the correct manufacture of sterile products. This training should include reference to hygiene and to the basic elements of microbiology. When outside staff who have not received such training (e.g. building or maintenance contractors) need to be brought in, particular care should be taken over their instruction and supervision. 所有在这些区域工作的人员（包括清洁和维护人员）都要定期进行与无菌药品生产有关的纪律培训。这些培训要包括卫生和微生物学的基本知识。当外来的没有接受培训的人员（如建造或维修人员）需要进入时，要特别注意给予指导和监督。
38. Staff who have been engaged in the processing of animal tissue materials or of cultures of micro-organisms other than those used in the current manufacturing process should not enter sterile-product areas unless rigorous and clearly defined entry procedures have been followed.从事动物组织加工处理或微生物培养的人员，不包括生产在用的材料，除非遵照严格明确的进入程序，不可进入洁净区。
39. High standards of personal hygiene and cleanliness are essential. Personnel involved in the manufacture of sterile preparations should be instructed to report any condition which may cause the shedding of abnormal numbers or types of contaminants; periodic health checks for such conditions are desirable. Actions to be taken about personnel who could be introducing undue microbiological hazard should be decided by a designated competent person. 高标准的人员卫生和清洁是非常关键的。要指导涉及生产的人员，及时报告可能产生异常污染的任何情况；要对人员定期进行健康检查。对可能带来微生物污染的人的处理措施，要由指定的合格的人员作出决定。
40. Wristwatches, make-up and jewellery should
not be worn in clean areas.
在洁净区内不准戴手表、首饰和化装。41. Changing and washing should follow a written 要按照书面的更换和清洗程序，尽可能降低
procedure designed to minimize contamination of clean area clothing or carry-through of contaminants to the clean areas. 对洁净区工作服的污染或将污染物带进洁净区。
42. The clothing and its quality should be appropriate for the process and the grade of the working area. It should be worn in such a way as to protect the product from contamination.工作服及其质量必须适应所从事的工作和工作场所的洁净级别。要正确穿戴，防止对产品产生污染。
43. The description of clothing required for each grade is given below: 下面对各个级别洁净区的工作服的要求进行说明：
Grade D: Hair and, where relevant, beard should be covered. A general protective suit and appropriate shoes or overshoes should be worn. Appropriate measures should be taken to avoid any contamination coming from outside the clean area.
Grade C: Hair and where relevant beard and moustache should be covered. A single or two-piece trouser suit, gathered at the wrists and with high neck and appropriate shoes or overshoes should be worn. They should shed virtually no fibres or particulate matter.
Grade A/B: Headgear should totally enclose hair and, where relevant, beard and moustache; it should be tucked into the neck of the suit; a face mask should be worn to prevent the shedding of droplets. Appropriate sterilised, non-powdered rubber or plastic gloves and sterilised or disinfected footwear should be worn. Trouser-legs should be tucked inside the footwear and garment sleeves into the gloves. The protective clothing should shed virtually no fibres or particulate matter and retain particles shed by the body. D级：头发和胡须要覆盖，要穿戴一般工作服和合适的工作鞋或鞋套。要采取适当措施防止污染物从外界进入洁净区。
C级要覆盖头发和所有胡须，要穿戴一件或两件套裤式、袖口收拢、高领的工作服，穿合适的工作鞋或鞋套。这些工作服都不得脱落纤维或颗粒。
A/B级：头套要覆盖所有的头发和胡须并要收紧在工作服领子内；要带口罩以防止液体飞沫的喷射。要穿戴正确消毒后的、不脱落粉尘的橡胶或塑料手套、灭菌或消毒的鞋子。袖口要塞进手套内，裤腿要塞进鞋子里。保护工作服要不脱落任何纤维或颗粒，并阻隔身体产生的颗粒。
44. Outdoor clothing should not be brought into changing rooms leading to grade B and C rooms. For every worker in a grade A/B area, clean sterile (sterilised or adequately sanitised) protective garments should be provided at each work session. Gloves should be regularly disinfected during operations. Masks and gloves should be changed at least for every working session. 外界的衣服不得带进通向B级和C级的更衣室。在A/B级区域工作的各个岗位工作的人员，要穿戴洁净服（灭菌的或充分消毒的）。在生产操作中要对手套定期消毒。每班都要更换口罩和手套。
45. Clean area clothing should be cleaned and handled in such a way that it does not gather additional contaminants which can later be shed. 洁净区工作服的清洁和处理的方法，要保证不吸附或携带随后又会脱落的污染物。这些操作要按照书面规程。这些工作服最好分开
These operations should follow written procedures. Separate laundry facilities for such clothing are desirable. Inappropriate treatment of clothing will damage fibres and may increase the risk of shedding of particles. 洗涤。对工作服不适当的处理方法会损害纤维、增加颗粒脱落的风险。
Premises 设施
46. In clean areas, all exposed surfaces should be smooth, impervious and unbroken in order to minimize the shedding or accumulation of particles or micro-organisms and to permit the repeated application of cleaning agents, and disinfectants where used. 在洁净区，所有暴露的表面都要光滑、不透水的和不破裂，以减少粉尘和微生物的脱落和累积，允许重复使用清洁剂和消毒剂。
47. To reduce accumulation of dust and to facilitate cleaning there should be no uncleanable recesses and a minimum of projecting ledges, shelves, cupboards and equipment. Doors should be designed to avoid those uncleanable recesses; sliding doors may be undesirable for this reason. 为减少粉尘的累积并且易于清洁，不能有清洁不到的角落，保持最少量的突出物、支架、厨柜和设备。门的设计要避免难清洁角落。该区域内不宜用拉门
48. False ceilings should be sealed to prevent
contamination from the space above them.
吊顶要密封，防止来自上面空间的污染。
49. Pipes and ducts and other utilities should be installed so that they do not create recesses, unsealed openings and surfaces which are difficult to clean. 管道和其他设施的安装不得产生死角、空隙或表面不易清洁。
50. Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture. In other areas air breaks should be fitted between the machine or sink and the drains. Floor drains in lower grade clean rooms should be fitted with traps or water seals to prevent back-flow. 用于无菌生产的A/B区不得设水池和地漏。其他区域的设备或水槽与排水系统间的空气要断路。低洁净级别区域的房间的地漏要有水弯或水封防止倒流。
51. Changing rooms should be designed as airlocks and used to provide physical separation of the different stages of changing and so minimize microbial and particulate contamination of protective clothing. They should be flushed effectively with filtered air. The final stage of the changing room should, in the at-rest state, be the same grade as the area into which it leads. The use of separate changing rooms for entering and leaving clean areas is sometimes desirable. In general hand washing facilities should be provided only in the first stage of the changing rooms. 更衣室要设计成气闸室，以提供不同阶段更衣的实际隔离，减少对工作服的微生物和尘埃粒子的污染。更衣室要经过过滤空气有效的冲洗。更衣室的最后阶段要与所进入的区域的洁净级别（静态）相一致。最好在进入洁净区和离开洁净区时使用不同的更衣室。一般洗手要在更衣的第一阶段。
52. Both airlock doors should not be opened simultaneously. An interlocking system or a visual and/or audible warning system should be operated 气闸室的两个门不可以同时打开。要有联锁装置，或视觉或听觉的报警装置，防止超过一个的门同时打开。
to prevent the opening of more than one door at a time.
53. A filtered air supply should maintain a positive pressure and an air flow relative to surrounding areas of a lower grade under all operational conditions and should flush the area effectively. Adjacent rooms of different grades should have a pressure differential of 10 – 15 pascals (guidance values). Particular attention should be paid to the protection of the zone of greatest risk, that is, the immediate environment to which a product and cleaned components which contact the product are exposed. The various recommendations regarding air supplies and pressure differentials may need to be modified where it becomes necessary to contain some materials, e.g. pathogenic, highly toxic, radioactive or live viral or bacterial materials or products. Decontamination of facilities and treatment of air leaving a clean area may be necessary for some operations. 过滤空气要对周围低级别区域保持相对的正气压和气流，并有效地冲洗整个区域。相邻的不同级别的房间要保持10-15 Pa的压差(指导值)。对高风险区域，即产品和与产品直接接触的洁净部件的暴露环境，要特别注意保护。对供气和压差方面的各种建议，在含有病原体、高毒性、放射性和有活病毒或活菌的原材料或产品的地方，可能需要修改。在一些操作中，对设备污染的清除和洁净区排风的处理是必要的
Equipment 设备
56. A conveyor belt should not pass through a partition between a grade A or B area and a processing area of lower air cleanliness, unless the belt itself is continually sterilised (e.g. in a sterilising tunnel). 传送带不可以穿过A/B级区和其他低洁净度处理区域的间隔，除非传送带被持续的灭菌（如在灭菌隧道中）。
57. As far as practicable equipment, fittings and services should be designed and installed so that operations, maintenance and repairs can be carried out outside the clean area. If sterilisation is required, it should be carried out, wherever possible, after complete reassembly. 设备、配件和设施要以能够在洁净区外面进行操作、维护和修理的方式进行设计和安装。重新安装后，如果需要消毒，在可能的地方要进行消毒
58. When equipment maintenance has been carried out within the clean area, the area should be cleaned, disinfected and/or sterilised where appropriate, before processing recommences if the required standards of cleanliness and/or asepsis have not been maintained during the work. 在洁净区内进行设备维护工作后，如果维修工作不能保持要求的清洁和无菌标准，要对该区域适当的地方进行清洁、消毒或灭菌。
59. Water treatment plants and distribution systems should be designed, constructed and maintained so as to ensure a reliable source of water of an appropriate quality. They should not be operated beyond their designed capacity. Water for injections should be produced, stored and 水处理和分配系统的设计、安装和维护要保证可靠的供水质量。系统的运行不可以超过设计的性能。注射用水的制备、储存和输送，要防止微生物的生长，例如在70°C以上持续循环。
distributed in a manner which prevents microbial growth, for example by constant circulation at a temperature above 70°C.
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. 所有设备如灭菌柜、空气处理和过滤系统、排风和气体过滤、水处理、制备、储存和输送系统都要进行验证和有计划地维护，重新使用要经过批准。
Sanitation 清洁卫生
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。在进行消毒的地方，要用一种以上的消毒剂。要定期进行监控，以检查抗性菌的生长。
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. 要对清洁剂和消毒剂进行微生物监控；稀释溶液要装在预先清洁的容器内，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. 对洁净区内难以进入的角落进行熏蒸是减少微生物污染的有用的方法。
Processing 生产
64. Precautions to minimize contamination should be taken during all processing stages including the stages before sterilisation. 在所有生产阶段，包括灭菌前各阶段，要注意采取措施预防和减少污染。
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. 微生物制品不能在其他药品生产使用的区域进行处理或灌装，但是死的微生物或细菌提取物的疫苗在灭活后可以在其他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. 无菌生产过程的验证，要包括利用营养培养基进行的模拟试验。要根据产品的剂型和培养基的选择性、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. 过程模拟试验要尽可能地接近正常的无菌生产程序，包括随后的各个关键生产步骤。同时要考虑在正常生产过程中的各种干预和挑战性状况。
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. 过程模拟试验在验证的开始阶段，要每个班次连续做三次满意的试验，在规定的时间间隔和空气处理系统、设备、生产工艺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重复两次过程模拟试验。
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: 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至少等于产品的批量。目标是零生长。并符合以下要求：
When filling fewer than 5000 units, no contaminated units should be detected. 当分装数量小于5000时，全部无菌.当分装数量在5000~10000之间时，出现一个染菌，应该调查，甚至考虑重新执行模拟测试；出现两个染菌就要重新验证，并调查原因。当分装数量大于10000时，出现一个染菌，应该调查原因；出现两个染菌就要重新验证，并调查原因。
When filling 5,000 to 10,000 units:
a) One (1) contaminated unit should result in an investigation, including consideration of a repeat media fill;
b) Two (2) contaminated units are considered cause for revalidation, following investigation.
When filling more than 10,000 units:
a) One (1) contaminated unit should result in an investigation;
b) Two (2) contaminated units are considered cause for revalidation, following investigation.
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. 对于任何批量，间歇性发生的微生物污染可能表明低程度的污染，应进行调查。调查应包括所有的潜在的影响因素，调查过程应该涉及自上次成功模拟测试以来的所有生产批次。
71. Care should be taken that any validation does
not compromise the processes.
应注意任何验证都不能危及生产过程。
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. 水源，水处理设备和制得的水应定期监测化学和生物污染，如有可能还应测试内毒素。监测的结果和采取的任何措施都应该记录。
73. Activities in clean area s 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. 在洁净区内，特别是当无菌生产在进行中，活动要尽可能少，人员的活动要受到控制并按照方法，避免由于过多活动带来尘埃颗粒和微生物的扩散。周围环境的温度和湿度不能高到不舒服，因为工作服是相当密封的。
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. 起始原料的微生物污染必须低。当指明该项目需要控制时，标准里要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. 容易产生纤维的容器和原料要尽量少进入洁净区
76. Where appropriate, measures should be taken to minimize the particulate contamination of the end product. 适当的条件下，要采取措施，减少对终产品的尘埃粒子的污染。
77. Components, containers and equipment should be handled after the final cleaning process in such a way that they are not recontaminated. 原辅料、容器和设备在进行清洁后，在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 minimized and subject to a time-limit appropriate to the storage conditions. 原辅料、容器、和设备的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，在规定的储存条件下要尽可能缩短，并控制在时间限度内。
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. 溶液的开始配制到灭菌或微孔过滤处理的时间间隔要尽可能短。应该根据产品的组分和规定的储存方法，设定最长允许时间。
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 在灭菌前要对微生物的含量进行监控。对于同灭菌方法的效果相关的灭菌前的步骤的污染，要有工作限度。适当的情况下，要对无热源进行监控。所有溶液，特别是大剂量注射液，要通过微生物过滤器，如果可能，过滤步骤紧接着灌装。
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.
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. 原辅料、容器、和设备以及其他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，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. 任何一个新程序的效果都要进行验证，要根据运行历史定期地，或当生产工艺或设备有重大改变时，对验证的结果进行再确认。
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. 所有灭菌过程都要进行验证，特别要注意现行欧洲药典没有采用的灭菌方法，或当所灭菌的产品不是简单的水溶液或油溶液时。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，灭菌方法必须与生产批文规定的方法一致。
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 在采用任何一种灭菌方法前，其对产品的适应性，和在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，要在适当情况下，用实际的测量或生物指示剂的方法进行证明。要定期验证过程的有效性，至少每年一次，并且在设备进行重大改变时要验证确认。对验证结果进行记录。
the results.
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. 为保持灭菌的有效性，所有的原料要按照要求进行处理，生产工艺的设计要保证这是能够实现的。
86. Validated loading patterns should be
established for all sterilisation processes.
要为所有的灭菌工艺建立验证的装载方式。
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. 要将生物指示作为灭菌监控的辅助手段。要按照操作指南进行储存和使用，并利用阳性控制检查其质量。如果采用了生物指示，要采取严格的措施，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 sterilized 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. 要有清楚的方法区分灭菌的和没有经过灭菌的产品。每一篮子、盘子或其他容器装的产品或原辅料要用物料名称、批号以及是否灭菌的指示清楚的标记。在适当的地方，可能使用灭菌指示带等指示来表明一批（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. 每一次灭菌都要有灭菌记录，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. 每一个加热灭菌循环都要在有足够大范围的时间/温度表上，或在其它有适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要在验证时予以确定，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. 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 在开始测定灭菌时间前，要有足够的时间让所有装载的产品达到规定的温度。对每种装
measurement of the sterilising time-period is
commenced. This time must be determined for
each type of load to be processed.
载要确定这个时间。
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. 在加热灭菌的高温阶段后，在冷却阶段要采取措施防止污染。任何与产品接触的冷却剂或气体都要进行灭菌，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. 使用温度和压力来监控灭菌过程。控制仪器与监控仪器和记录表是各自独立的。如果采用自动化的控制和监控系统，要进行验证，保证达到关键生产工艺要求。系统的和周期性的故障要通过系统进行记录和由操作者进行观察。要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柜，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，要经常进行泄露检查。
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. 如果灭菌的产品不是在密封的容器里，要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，都要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. 要注意保证灭菌所用的蒸汽的质量，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 该工艺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。所有进入的空气必须通过HEPA过滤器。如果该工艺也
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. 用于出去热源，用内毒素进行挑战性实验是验证的一部分
Sterilisation by radiation 辐射灭菌
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. 辐射灭菌主要用于热敏感的材料或产品的灭菌。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。紫外辐射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.在灭菌过程中，放射剂量要进行测定。因此，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。将足够数量的剂量计插入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，要确保在它们的校验期内。剂量计的吸光度要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
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.验证过程要保证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. 材料的处理要防止照射过的和没有照射过的材料的混淆。在每个包装上使用光敏感的色片，来区分已经照射过的和未照射的产品
103. The total radiation dose should be administered within a predetermined time span. 要在预先规定的时间范围内完成总的照射剂量
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 这种方法只是在没有其它合适方法的情况下使用。在验证过程中，要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。
reaction products to defined acceptable limits for the type of product or material.
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. 气体和微生物细胞的直接接触是关键；要注意避免生物体包裹在诸如晶体或干的蛋白质内。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. 在与气体接触前，材料要达到工艺要求的温度和湿度。需要的时间要同相反的需要平衡，从而使灭菌前时间最小。
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. 每一次的灭菌循环都要用合适的微生物指示剂进行监控，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要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. 每一个灭菌循环的记录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要记录在图纸上。记录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. 灭菌后，产品要保存在控制状态下，保持通风条件，使残留气体和反应产物降低到规定的水平。此过程要进行验证。
101. Validation procedures should ensure that the effects of variations in density of the packages are considered.验证过程要保证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. 材料的处理要防止照射过的和没有照射过的材料的混淆。在每个包装上使用光敏感的色片，来区分已经照射过的和未照射的产品
103. The total radiation dose should be administered within a predetermined time span. 要在预先规定的时间范围内完成总的照射剂量
Filtration of medicinal products which 不能在最终容器内进行灭菌的