2022版欧盟GMP附录《无菌药品的生产》

2011年版中国GMP附录《无菌药品》

共11章295条款

共15章81条款

1.Scope范围

第一章范围

2.Principle原则

第二章原则

3.Pharmaceutical Quality System(PQS)制药质量体系PQS

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4.Premise设施

第七章厂房

第四章隔离操作技术（部分）

5.Equipment设备

第八章设备

6.Utilities公用系统

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7.Personnel人员

第六章人员

8.Production and specific technologies生产和特定技术

第四章隔离操作技术（部分）

第五章吹灌封技术

第九章消毒

第十章生产管理

第十一章灭菌工艺

第十二章灭菌方法

第十三章无菌药品的最终处理

9.Environmental and process monitoring环境和工艺监测

第三章洁净度级别及监测

10.Quality control(QC)质量控制（QC）

第十四章质量控制

11.Glossary术语

第十五章术语

关键词

频数

Cleanroom - 洁净室

91

Aseptic preparation/processing - 无菌制备 / 加工

58

Aseptic Process Simulation (APS) - 无菌过程模拟 (APS)

53

Contamination Control Strategy (CCS) - 污染控制策略 (CCS)

51

Sterile Product - 无菌产品

48

Isolator - 隔离器

48

Operator - 操作员

35

Pyrogen - 热原

32

Disinfection - 消毒

31

Endotoxin - 内毒素

29

Cleaning - 清洁

29

Restricted Access Barrier System (RABS) - 限制进入屏障系统 (RABS)

27

Critical zone - 关键区域

25

Unidirectional airflow - 单向气流

22

Airlock - 气闸

20

Bioburden - 生物负荷

19

Sterilising grade filter - 灭菌级过滤器

18

Decontamination - 去污

18

Bio-decontamination - 消毒

18

Single Use Systems (SUS) - 一次性使用系统 (SUS)

17

Colony Forming Unit (CFU) - 菌落形成单位 (CFU)

17

Alert level - 警戒限

17

Barrier - 隔离技术

16

Lyophilization - 冻干

15

Gowning qualification - 更衣确认

15

Blow-Fill-Seal (BFS) - 吹灌封技术

15

Action limit - 行动限

15

Manual aseptic processing- 手动无菌处理

14

Closed system - 密闭系统

12

Worst case - 最差情形

11

Form-Fill-Seal (FFS) - 成型 - 灌装 - 密封 (FFS)

10

Clean area - 洁净区

10

Water system - 水系统

9

Terminal Sterilisation - 终端灭菌

8

Parison - 半成品

8

Grade A air supply -A 级送风

7

First Air - 首过空气

7

Biological Indicators (BI) - 生物指示剂

7

Patient - 患者

6

Pass-through hatch - 传递舱

6

Intrinsic sterile connection device - 内在无菌连接装置

6

Cleanroom classification - 洁净室分类

6

D-value - D 值

5

Depyrogenation - 去热原

5

Critical intervention - 关键干预

5

Contamination - 污染

5

Cleanroom qualification - 洁净室确认

5

Turbulent airflow - 湍流

4

Raw material - 原材料

4

HEPA filter - HEPA 过滤器

4

Critical surfaces - 关键表面

4

Classified area - 分类区域

4

Bacterial retention testing - 细菌截留测试

4

Sporicidal agent - 杀孢子剂

3

Post-aseptic processing terminal heat treatment - 无菌加工后终端热处理

3

Leachables - 浸出物

3

Isokinetic sampling head - 等速采样头

3

Filter Integrity test - 过滤器完整性测试

3

Asepsis - 无菌

3

Z-value - Z 值

2

Unidirectional Airflow (UDAF) unit - 单向气流 (UDAF) 单元

2

Rapid Transfer System/Port (RTP) - 快速转移系统 / 端口 (RTP)

2

Overkill sterilisation - 过度杀灭灭菌

2

Local isolates - 本地分离物

2

Inherent interventions - 常规干预

2

Extractables - 可提取物

2

Equilibration time - 平衡时间

2

Decommission - 报废

2

Dead leg - 死角

2

Corrective intervention - 纠正性干预

2

Campaign manufacture - 连续生产

2

关键术语

Airlock - An enclosed space with interlocked doors, constructed to maintain air pressure control between adjoining rooms (generally with different air cleanliness standards). The intent of an airlock is to preclude ingress of particle matter and microorganism contamination from a lesser controlled area.

气闸 - 带有互锁门的封闭空间，用于保持相邻房间之间的气压控制（通常具有不同的空气清洁度标准）。气闸的目的是防止颗粒物质和微生物污染从控制较少的区域进入。

Action limit - An established relevant measure (e.g. microbial, or airborne particle limits) that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation.

行动限 - 既定的相关措施（例如微生物或空气中的颗粒物限制），当超过该限制时，应触发适当的调查和基于调查的纠正措施。

Alert level - An established relevant measure (e.g. microbial, or airborne particle levels) giving early warning of potential drift from normal operating conditions and validated state, which does not necessarily give grounds for corrective action but triggers appropriate scrutiny and follow-up to address the potential problem. Alert levels are established based on routine and qualification trend data and are periodically reviewed. The alert level can be based on a number of parameters including adverse trends, individual excursions above a set limit and repeat events.

警戒限 - 一种既定的相关措施（例如微生物或空气中的颗粒物水平），对从正常操作条件和验证状态的潜在漂移发出早期警告，不一定为纠正措施提供理由，但会触发适当的审查和后续行动以解决问题潜在的问题。警戒限是根据常规和确认趋势数据建立的，并定期进行审查。警报级别可以基于多个参数，包括不利趋势、超出设定限制的个别偏移和重复事件。

Aseptic preparation/processing - The handling of sterile product, containers and/or devices in a controlled environment in which the air supply, materials and personnel are regulated to prevent microbial, endotoxin/pyrogen and particle contamination.

无菌制备/加工——在受控环境中处理无菌产品、容器和/或装置，在该环境中对空气供应、材料和人员进行监管，以防止微生物、内毒素/热原和颗粒污染。

Aseptic Process Simulation (APS) - A simulation of the entire aseptic manufacturing process in order to verify the capability of the process to assure product sterility. Includes all aseptic operations associated with routine manufacturing, e.g. equipment assembly, formulation, filling, lyophilization and sealing processes as necessary.

无菌过程模拟 (APS) - 整个无菌生产过程的模拟，以验证该过程确保产品无菌的能力。包括与常规生产相关的所有无菌操作，例如必要时进行设备组装、配制、灌装、冻干和密封过程。

Asepsis - A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbial contamination of the exposed sterile product.

无菌 - 通过使用无菌工作区域并以排除暴露的无菌产品的微生物污染的方式进行活动而获得的控制状态。

Bacterial retention testing - This test is performed to validate that a filter can remove bacteria from a gas or liquid. The test is usually performed using a standard organism, such as Brevundimonas diminuta at a minimum concentration of 10⁷ Colony Forming Units/cm².

细菌截留测试- 执行此测试以验证过滤器是否可以从气体或液体中去除细菌。该测试通常使用标准生物体进行，例如最小浓度为 10⁷ 个菌落形成单位/cm2 的缺陷短波单胞菌。

Barrier - A physical partition that affords aseptic processing area (usually grade A) protection by separating it from the background environment. Such systems frequently use in part or totally the Barrier Technologies known as RABS or isolators.

隔离技术 - 通过将无菌处理区（通常为 A 级）与背景环境隔开来提供无菌处理区（通常为 A 级）保护的物理分区。此类系统经常部分或全部使用称为 RABS 或隔离器的屏障技术。

Bioburden - The total number of microorganisms associated with a specific item such as personnel, manufacturing environments (air and surfaces), equipment, product packaging, raw materials (including water), in-process materials, or finished products.

生物负荷 - 与特定项目相关的微生物总数，例如人员、生产环境（空气和表面）、设备、产品包装、原材料（包括水）、加工材料或成品。

Bio-decontamination - A process that eliminates viable bioburden via use of sporicidal chemical agents.

消毒 - 通过使用杀孢子化学试剂消除可行生物负载的过程。

Biological Indicators (BI) - A population of microorganisms inoculated onto a suitable medium (e.g. solution, container or closure) and placed within a steriliser or load or room locations to determine the sterilisation or disinfection cycle efficacy of a physical or chemical process. The challenge microorganism is selected and validated based upon its resistance to the given process. Incoming lot D-value, microbiological count and purity define the quality of the BI.

生物指示剂 (BI) - 接种到合适介质（例如溶液、容器或封闭物）上并放置在灭菌器或负载或房间位置的微生物群，以确定物理或化学过程的灭菌或消毒循环效率。挑战微生物是根据其对给定过程的抗性来选择和验证的。进货批次 D 值、微生物计数和纯度决定了 BI 的质量。

Blow-Fill-Seal (BFS) - A technology in which containers are formed from a thermoplastic granulate, filled with product, and then sealed in a continuous, integrated, automatic operation. The two most common types of BFS machines are the Shuttle type (with Parison cut) and the Rotary type (Closed Parison).

吹灌封技术(BFS) - 一种技术，其中容器由热塑性颗粒制成，填充产品，然后在连续、集成、自动操作中密封。两种最常见的 BFS 机器类型是梭式（带型坯切割）和旋转型（封闭型坯）。

Campaign manufacture - A manufacture of a series of batches of the same product in sequence in a given period of time with strict adherence to established and validated control measures.

连续生产 - 在给定的时间段内按顺序生产一系列批次的相同产品，并严格遵守既定且经过验证的控制措施。

Classified area - An area that contains a number of cleanrooms (see cleanroom definition).

分类区域 - 包含多个洁净室的区域（参见洁净室定义）。

Cleaning - A process for removing contamination e.g. product residues or disinfectant residues.

清洁 - 去除污染物的过程，例如产品残留物或消毒剂残留物。

Clean area - An area with defined particle and microbiological cleanliness standards usually containing a number of joined cleanrooms.

洁净区 - 具有明确的颗粒和微生物洁净度标准的区域，通常包含多个相连的洁净室。

Cleanroom - A room designed, maintained, and controlled to prevent particle and microbial contamination of drug products. Such a room is assigned and reproducibly meets an appropriate air cleanliness level.

洁净室——设计、维护和控制以防止药物产品受到颗粒和微生物污染的房间。这样的房间被分配并且可重复地满足适当的空气清洁度水平。

Cleanroom classification - A method of assessing the level of air cleanliness against a specification for a cleanroom or clean air equipment by measuring the total particle concentration.

洁净室分类 - 一种通过测量总颗粒浓度来根据洁净室或洁净空气设备规范评估空气洁净度水平的方法。

Cleanroom qualification - A method of assessing the level of compliance of a classified cleanroom or clean air equipment with its intended use.

洁净室确认 - 一种评估分类洁净室或洁净空气设备是否符合其预期用途的方法。

Closed system - A system in which the product is not exposed to the surrounding environment. For example, this can be achieved by the use of bulk product holders (such as tanks or bags) that are connected to each other by pipes or tubes as a system, and where used for sterile products, the full system is sterilised after the connections are made. Examples of these can be (but are not limited to) large scale reusable systems, such as those seen in active substance manufacturing, or disposable bag and manifold systems, such as those seen in the manufacture of biological products. Closed systems are not opened until the conclusion of an operation. The use of the term “closed systems” in this Annex does not refer to systems such as RABS or isolator systems.

密闭系统 - 产品不暴露于周围环境的系统。例如，这可以通过使用通过管道或管子相互连接的散装产品支架（例如罐或袋子）作为一个系统来实现，并且在用于无菌产品的情况下，整个系统在连接后进行消毒被制作。这些示例可以是（但不限于）大规模可重复使用系统，例如在活性物质生产中看到的那些，或一次性袋子和歧管系统，例如在生物产品生产中看到的那些。在操作结束之前，封闭的系统不会打开。本附录中使用的术语“封闭系统”并不指 RABS 或隔离系统等系统。

Colony Forming Unit (CFU) - A microbiological term that describes a single detectable colony that originates from one or more microorganisms. Colony forming units are typically expressed as CFU per ml for liquid samples, CFU per m³ for air sample and CFU per sample for samples captured on solid medium such as settle or contact plates.

菌落形成单位 (CFU) - 一个微生物学术语，描述源自一种或多种微生物的单个可检测菌落。对于液体样品，菌落形成单位通常表示为每毫升 CFU，对于空气样品，每立方米 CFU，对于在固体介质（如沉降或接触板）上捕获的样品，菌落形成单位通常表示为每样品 CFU。

Contamination - The undesired introduction of impurities of a microbiological nature (quantity and type of microorganisms, pyrogen), or of foreign particle matter, into or onto a raw material, intermediate, active substance or drug product during production, sampling, packaging or repackaging, storage or transport with the potential to adversely impact product quality.

污染 - 在生产、取样、包装或重新包装过程中，将微生物性质的杂质（微生物的数量和类型、热原）或外来颗粒物质不希望地引入原材料、中间体、活性物质或药物产品中或之上，可能对产品质量产生不利影响的储存或运输。

Contamination Control Strategy (CCS) - A planned set of controls for microorganisms, endotoxin/pyrogen and particles, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to active substance, excipient and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

污染控制策略 (CCS) - 一套针对微生物、内毒素/热原和颗粒的计划控制，源自对当前产品和工艺的理解，可确保工艺性能和产品质量。控制可以包括与活性物质、赋形剂和药品材料和组件、设施和设备操作条件、过程控制、成品规格以及相关的监测和控制方法和频率相关的参数和属性。

Corrective intervention - An intervention that is performed to correct or adjust an aseptic process during its execution. These may not occur at a set frequency in the routine aseptic process. Examples include such as clearing component jams, stopping leaks, adjusting sensors, and replacing equipment components.

纠正性干预——在执行过程中纠正或调整无菌过程的干预。这些可能不会在常规无菌过程中以设定的频率发生。示例包括清除组件堵塞、停止泄漏、调整传感器和更换设备组件。

Critical surfaces - Surfaces that may come directly into contact with, or directly affect, a sterile product or its containers or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation, and sterility is maintained throughout processing.

关键表面 - 可能直接接触或直接影响无菌产品或其容器或封闭件的表面。关键表面在生产操作开始前进行无菌处理，并在整个加工过程中保持无菌状态。

Critical zone - A location within the aseptic processing area in which product and critical surfaces are exposed to the environment.

关键区域——无菌加工区内产品和关键表面暴露于环境中的位置。

Critical intervention - An intervention (corrective or inherent) into the critical zone.

关键干预 - 对关键区域的干预（纠正或固有）。

D-value - The value of a parameter of sterilisation (duration or absorbed dose) required to reduce the number of viable organisms to 10 per cent of the original number.

D 值 - 将活生物的数量减少到原始数量的 10% 所需的灭菌参数值（持续时间或吸收剂量）。

Dead leg - Length of non-circulating pipe (where fluid may remain static) that is greater than 3 internal pipe diameters.

死角 - 大于 3 个内部管道直径的非循环管道（流体可能保持静止）的长度。

Decommission - When a process, equipment or cleanroom are closed and they will not be used again.

报废  - 当工艺、设备或洁净室关闭且不再使用时。

Decontamination - The overall process of removal or reduction of any contaminants (chemical, waste, residue or microorganisms) from an area, object, or person. The method of decontamination used (e.g. cleaning, disinfection, sterilisation) should be chosen and validated to achieve a level of cleanliness appropriate to the intended use of the item decontaminated. See also Bio-decontamination.

去污——从一个区域、物体或人中去除或减少任何污染物（化学物质、废物、残留物或微生物）的整个过程。应选择并验证所使用的去污方法（例如清洁、消毒、灭菌），以达到适合去污物品预期用途的清洁度水平。另见生物净化。

Depyrogenation - A process designed to remove or inactivate pyrogenic material (e.g. endotoxin) to a specified minimum quantity.

去热原 - 旨在将热原物质（例如内毒素）去除或灭活到指定的最小量的过程。

Disinfection - The process by which the reduction of the number of microorganisms is achieved by the irreversible action of a product on their structure or metabolism, to a level deemed to be appropriate for a defined purpose.

消毒——通过产品对其结构或新陈代谢的不可逆作用，将微生物数量减少到被认为适合特定目的的水平的过程。

Endotoxin - A pyrogenic product (i.e. lipopolysaccharide) present in the Gram negative bacterial cell wall. Endotoxin can lead to reactions in patients receiving injections ranging from fever to death.

内毒素 - 存在于革兰氏阴性细菌细胞壁中的热原产物（即脂多糖）。内毒素可导致接受注射的患者出现从发烧到死亡的反应。

Equilibration time - Period which elapses between the attainment of the sterilisation temperature at the reference measurement point and the attainment of the sterilisation temperature at all points within the load.

平衡时间——在参考测量点达到灭菌温度和负载内所有点达到灭菌温度之间经过的时间。

Extractables - Chemical entities that migrate from the surface of the process equipment, exposed to an appropriate solvent at extreme conditions, into the product or material being processed.

可提取物 - 从工艺设备表面迁移到极端条件下暴露于适当溶剂中的化学实体，进入正在加工的产品或材料中。

First Air - Refers to filtered air that has not been interrupted prior to contacting exposed product and product contact surfaces with the potential to add contamination to the air prior to reaching the critical zone.

首过空气 - 指在接触暴露的产品和产品接触表面之前没有中断的过滤空气，有可能在到达关键区域之前对空气增加污染。

Filter Integrity test - A test to confirm that a filter (product, gas or HVAC filter) retain their retentive properties and have not been damaged during handling, installation or processing.

过滤器完整性测试 - 确认过滤器（产品、气体或 HVAC 过滤器）保持其保持性能并且在处理、安装或加工过程中没有损坏的测试。

Form-Fill-Seal (FFS) -An automated filling process, typically used for terminally sterilised products, which constructs the primary container out of a continuous flat roll of packaging film while simultaneously filling the formed container with product and sealing the filled containers in a continuous process. FFS processes may utilize a single web system (where a single flat roll of film is wrapped around itself to form a cavity), or a dual web system (where two flat rolls of film are brought together to form a cavity), often with the aid of vacuum moulds or pressurised gases. The formed cavity is filled, sealed and cut into sections. Films typically consist of a polymeric material, polymeric coated foil or other suitable material.

成型-灌装-密封 (FFS) - 一种自动灌装工艺，通常用于最终灭菌的产品，该工艺由连续扁平的包装薄膜卷构成主容器，同时用产品填充成型容器并将填充的容器密封在连续过程。 FFS 工艺可以使用单幅系统（其中单个扁平薄膜卷缠绕在自身周围以形成空腔）或双幅系统（其中将两个扁平薄膜卷放在一起以形成空腔），通常使用借助真空模具或加压气体。形成的空腔被填充、密封并切成段。薄膜通常由聚合物材料、聚合物涂层箔或其他合适的材料组成。

Gowning qualification - A programme that establishes, both initially and on a periodic basis, the capability of an individual to don the complete gown.

更衣确认 - 一项计划，在初始和定期的基础上，确定个人完整更衣的能力。

Grade A air supply - Air which is passed through a filter qualified as capable of producing grade A total particle quality air, but where there is no requirement to perform continuous total particle monitoring or meet grade A viable monitoring limits. Specifically used for the protection of fully stoppered vials where the cap has not yet been crimped.

A 级送风 - 通过过滤器的空气能够产生 A 级总颗粒质量空气，但不需要执行连续总颗粒监测或满足 A 级可行监测限制。专门用于保护瓶盖尚未压接的全塞小瓶。

HEPA filter - High efficiency particulate air filter specified in accordance with a relevant international standard.

HEPA 过滤器 - 根据相关国际标准指定的高效微粒空气过滤器。

Inherent interventions - An intervention that is an integral part of the aseptic process and is required for either set-up, routine operation and/or monitoring (e.g. aseptic assembly, container replenishment, environmental sampling). Inherent interventions are required by procedure or work instruction for the execution of the aseptic process.

常规干预——作为无菌工艺不可分割的一部分，设置、常规操作和/或监控（例如，无菌组装、容器补充、环境采样）所需的干预。执行无菌过程的程序或工作指令需要固有的干预措施。

Intrinsic sterile connection device - A device that reduces the risk of contamination during the connection process; these can be mechanical or fusion sealing.

内在无菌连接装置——在连接过程中降低污染风险的装置；这些可以是机械密封或熔接密封。

Isokinetic sampling head - A sampling head designed to disturb the air as little as possible so that the same particles go into the nozzle as would have passed the area if the nozzle had not been there (i.e. the sampling condition in which the mean velocity of the air entering the sample probe inlet is nearly the same (± 20 percent) as the mean velocity of the airflow at that location).

等速采样头 - 一种采样头，设计用于尽可能少地扰动空气，以便进入喷嘴的相同颗粒在没有喷嘴的情况下会通过该区域（即采样条件中的平均速度进入样品探针入口的空气几乎与该位置的平均气流速度相同（± 20%）。

Isolator - An enclosure capable of being subject to reproducible interior bio-decontamination, with an internal work zone meeting grade A conditions that provides uncompromised, continuous isolation of its interior from the external environment (e.g. surrounding cleanroom air and personnel). There are two major types of isolators:

隔离器 - 能够进行可重复的内部生物净化的外壳，其内部工作区满足 A 级条件，可将其内部与外部环境（例如周围的洁净室空气和人员）毫不妥协地持续隔离。有两种主要类型的隔离器：

i. Closed isolator systems exclude external contamination of the isolator’s interior by accomplishing material transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding environment. Closed systems remain sealed throughout operations. 封闭式隔离器系统通过与辅助设备的无菌连接完成材料转移，而不是使用通往周围环境的开口，从而排除了隔离器内部的外部污染。封闭系统在整个操作过程中保持密封。

ii. Open isolator systems are designed to allow for the continuous or semi-continuous ingress and/or egress of materials during operations through one or more openings. Openings are engineered (e.g. using continuous overpressure) to exclude the entry of external contaminant into the isolator. 开放式隔离系统设计为允许材料在操作期间通过一个或多个开口连续或半连续进入和/或排出。设计开口（例如使用连续超压）以排除外部污染物进入隔离器。

Leachables - Chemical entities that migrate into products from the product contact surface of the process equipment or containers under normal condition of use and/or storage.

浸出物 - 在正常使用和/或储存条件下，从工艺设备或容器的产品接触表面迁移到产品中的化学实体。

Local isolates - Suitably representative microorganisms of the site that are frequently recovered through environmental monitoring within the classified zone/areas especially grade A and B areas, personnel monitoring or positive sterility test results.

本地分离物——通过分类区域/区域内的环境监测，特别是 A 级和 B 级区域内的环境监测、人员监测或阳性无菌检测结果，经常回收的具有代表性的现场微生物。

Lyophilization - A physical-chemical drying process designed to remove solvents, by way of sublimation, from both aqueous and non-aqueous systems, primarily to achieve product or material stability. Lyophilization is synonymous to the term freeze-drying.

冻干 - 一种物理化学干燥过程，旨在通过升华从水性和非水性系统中去除溶剂，主要是为了实现产品或材料的稳定性。冻干是术语冷冻干燥的同义词。

Manual aseptic processing- An aseptic process where the operator manually compounds, fills, places and /or seals an open container with sterile product.

手动无菌处理- 操作员手动混合、填充、放置和/或密封装有无菌产品的开口容器的无菌过程。

Operator - Any individual participating in the processing operation, including line set-up, filling, maintenance, or other personnel associated with manufacturing activities.

操作员 - 参与加工操作的任何个人，包括生产线设置、灌装、维护或与生产活动相关的其他人员。

Overkill sterilisation - A process that is sufficient to provide at least a 12 logw reduction of microorganisms having a minimum D-value of 1 minute.

过度杀灭灭菌 - 足以提供至少 12 logw 的微生物减少的过程，具有 1 分钟的最小 D 值。

Parison - The "tube" of polymer extruded by the BFS machine from which containers are formed.

半成品 - 由 BFS 机器挤出的聚合物“管”，从中形成容器。

Pass-through hatch - Synonymous with airlock (see airlock definition) but typically smaller in size.

传递舱 - 与气闸同义（参见气闸定义），但通常尺寸较小。

Patient - Human or animal including participants in a clinical trial.

患者 - 人类或动物，包括临床试验的参与者。

Post-aseptic processing terminal heat treatment - A terminal moist heat process employed after aseptic processing which has been demonstrated to provide a sterility assurance level (SAL) <10^-6 but where the requirements of steam sterilisation (for example, Fq>8 min) are not fulfilled. This may also be beneficial in the destruction of viruses that may not be removed through filtration.

无菌加工后终端热处理——无菌加工后采用的终端湿热工艺，已证明可提供 <10-6 的无菌保证水平 (SAL)，但需要蒸汽灭菌（例如，FQ>8 分钟）没有实现。这也可能有利于破坏可能无法通过过滤去除的病毒。

Pyrogen - A substance that induces a febrile reaction in patients receiving injections;

热原 - 一种在接受注射的患者中引起发热反应的物质；

Rapid Transfer System/Port (RTP) - A System used for the transfer of items into RABS or isolators that minimizes the risk to the critical zone. An example would be a rapid transfer container with an alpha/beta port.

快速转移系统/端口 (RTP) - 用于将物品转移到 RABS 或隔离器中的系统，可最大限度地降低对关键区域的风险。一个例子是带有 alpha/beta 端口的快速转运集装箱。

Raw material - Any ingredient intended for use in the manufacture of a sterile product, including those that may not appear in the final drug product.

原材料 - 用于生产无菌产品的任何成分，包括那些可能不会出现在最终药品中的成分。

Restricted Access Barrier System (RABS) - System that provides an enclosed, but not fully sealed, environment meeting defined air quality conditions (for aseptic processing grade A), and using a rigid-wall enclosure and integrated gloves to separate its interior from the surrounding cleanroom environment. The inner surfaces of the RABS are disinfected and decontaminated with a sporicidal agent. Operators use gloves, half suits, RTPs and other integrated transfer ports to perform manipulations or convey materials to the interior of the RABS. Depending on the design, doors are rarely opened, and only under strictly pre-defined conditions.

限制进入屏障系统 (RABS) - 提供封闭但非完全密封的环境，满足规定的空气质量条件（用于 A 级无菌加工），并使用刚性壁外壳和集成手套将其内部与周围环境隔开的系统洁净室环境。 RABS 的内表面使用杀孢子剂进行消毒和去污。操作员使用手套、半套装、RTP 和其他集成传输端口来执行操作或将材料传送到 RABS 内部。根据设计，门很少打开，只有在严格预先定义的条件下。

Single Use Systems (SUS) - Systems in which product contact components are used only once to replace reusable equipment such as stainless steel transfer lines or bulk containers. SUS covered in this document are those that are used in manufacturing processes of sterile products and are typically made up of disposable components such as bags, filters, tubing, connectors, storage bottles and sensors.

一次性使用系统 (SUS) - 产品接触部件仅使用一次以替换可重复使用的设备（如不锈钢传输线或散装容器）的系统。本文档中涵盖的 SUS 是用于无菌产品生产过程的那些，通常由一次性组件组成，例如袋子、过滤器、管道、连接器、储存瓶和传感器。

Sporicidal agent - An agent that destroys bacterial and fungal spores when used in sufficient concentration for specified contact time. It is expected to kill all vegetative microorganisms.

杀孢子剂 - 在指定接触时间内以足够浓度使用时可破坏细菌和真菌孢子的药剂。预计会杀死所有的植物性微生物。

Sterile Product - For purpose of this guidance, sterile product refers to one or more of the sterilised elements exposed to aseptic conditions and ultimately making up the sterile active substance or finished sterile product. These elements include the containers, closures, and components of the finished drug product. Or, a product that is rendered sterile by a terminal sterilisation process.

无菌产品——就本指南而言，无菌产品是指一种或多种暴露于无菌条件下并最终构成无菌活性物质或无菌成品的无菌元件。这些元素包括容器、封闭物和成品药的组件。或者，通过最终灭菌过程变得无菌的产品。

Sterilising grade filter - A filter that, when appropriately validated, will remove a defined microbial challenge from a fluid or gas producing a sterile effluent. Usually such filters have a pore size equal or less than 0.22 μ m.

灭菌级过滤器 - 一种过滤器，在经过适当验证后，将从产生无菌流出物的流体或气体中去除特定的微生物挑战。通常此类过滤器的孔径等于或小于 0.22 μm。

Terminal Sterilisation - The application of a lethal sterilising agent or conditions to a product in its final container to achieve a predetermined sterility assurance level (SAL) of 10 ⁶ or better (e.g. the theoretical probability of there being a single viable microorganism present on or in a sterilised unit is equal to or less than 1 x 1Q^-6 (one in a million)).

终端灭菌——在最终容器中对产品应用致命的灭菌剂或条件，以达到 10 6 或更高的预定无菌保证水平 (SAL)（例如，理论上存在单个活微生物的概率）灭菌单位等于或小于 1 x 1Q-6（百万分之一）。

Turbulent airflow - Air that is not unidirectional. Turbulent air in cleanrooms should flush the cleanroom via mixed flow dilution and ensure maintenance of acceptable air quality.

湍流 - 非单向的空气。洁净室中的湍流空气应通过混流稀释冲洗洁净室，并确保维持可接受的空气质量。

Unidirectional airflow - An airflow moving in a single direction, in a robust and uniform manner, and at sufficient speed, to reproducibly sweep particles away from the critical processing or testing area.

单向气流 - 以稳定且均匀的方式并以足够的速度在单一方向上移动的气流，可重复地将颗粒从关键处理或测试区域扫走。

Unidirectional Airflow (UDAF) unit - A cabinet supplied with filtered unidirectional airflow (previously referred to as a Laminar Airflow Unit or LAF).

单向气流 (UDAF) 单元 - 提供过滤单向气流的机柜（以前称为层流单元或 LAF）。

Worst case - A set of conditions encompassing processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared with ideal conditions). Such conditions have the highest potential to, but do not necessarily always result in product or process failure.

最差情形 - 包含工艺限制和环境的一组条件，包括标准操作程序中的条件，这些条件造成工艺或产品故障的可能性最大（与理想条件相比）。这种情况最有可能但不一定总是导致产品或过程失败。

Water system - A system for producing, storing and distributing water, usually compliant to a specific pharmacopeia grade (e.g. purified water and water for injection (WFI)).

水系统 - 用于生产、储存和分配水的系统，通常符合特定药典等级（例如纯净水和注射用水 (WFI)）。

Z-value - The temperature difference that leads to a 10-fold change in the D-value of the biological indicators.

Z 值 - 导致生物指示剂 D 值变化 10 倍的温差。