12. Change control 变更控制
12.1 Changes should be controlled in accordance with a SOP as changes may have an impact on a quali?ed utility, system or piece of equipment, and a validated process and/or procedure.
因为变更可能会对确认过的公用工程、系统或设备、已验证的工艺和/或程序产生影响，所以要按照SOP对变更进行控制。
12.2 The procedure should describe the actions to be taken, including the need for and extent of quali?cation or validation to be done.
在变更的控制程序中，应说明需要采取的措施，包括阐明是否需要确认或验证，以及需要执行的确认或验证的等级。
12.3 Changes should be formally requested, documented and approved before implementation. Records should be maintained.
应正式提出变更请求，而后对变更进行记录和审批，最后得到批准的变更方可执行。变更记录要保存。 53 Personnel 人员
13.1 Personnel should demonstrate that they are appropriately quali? ed, where relevant.
应证明人员拥有相应的资格。
13.2 Personnel requiring quali?cation include, for example: 以下是需要进行资格确认的人员的例子：
54 — laboratory analysts; 试验室的检验员；
55 — personnel following critical procedures; 实施关键步骤的人员；
56 — personnel doing data entry in computerized systems; and 负责将数据录入计算机系统的人员；以及 57 — risk assessors. 风险评估员。
Appendix 1 附录 1
Validation of heating, ventilation and air-conditioning systems
采暖、通风和空气净化系统的验证
58 General 概要
59 Commissioning 试运行 60 Quali?cation 确认
61 Reference 参考资料
1. General 概要
1.1 The heating, ventilation and air-conditioning (HVAC) system plays an important role in the protection of the product, the personnel and the environment. 采暖、通风和空气净化（HVAC）系统在保护产品、人员和环境上扮演着重要的角色。
1.2 For all HVAC installation components, subsystems or parameters, critical parameters and non-critical parameters should be determined.
应确定HVAC的所有安装部件、下游系统或参数、关键参数和非关键参数。 1.3 Some of the parameters of a typical HVAC system that should be quali? ed include:
需要确认的典型的HVAC系统的某些参数有：
62 — room temperature and humidity; 室内温度和湿度；
63 — supply air and return air quantities; 供风和回风量；
64 — room pressure, air change rate, ?ow patterns, particle count and cleanup rates; and
室内压力、空气交换率、气流类型、粒子计数和清除率；以及 65 — unidirectional ?ow velocities and HEPA ?lter penetration tests. 单向气流的流速和HEPA过滤器的渗透试验。
2. Commissioning 试运行
2.1 Commissioning should involve the setting up, balancing, adjustment and testing of the entire HVAC system, to ensure that the system meets all the requirements, as speci?ed in the user requirement speci? cation, and capacities as speci?ed by the designer or developer.
试运行应包括整个HVAC系统的安装、平衡、调整和测试，以确保该系统符合用户需要说明书中规定的所有要求，并证明该系统可实现设计者或研发者所定义的性能。
2.2 The installation records of the system should provide documented evidence of all measured capacities of the system.
系统的安装记录应包括已测试的该系统的所有性能的资料。
2.3 The data should include items such as the design and measured ?gures for air?ows, water ?ows, system pressures and electrical amperages. These should be contained in the operating and maintenance manuals (O & M manuals).
需要记录的数据应当包括气流、水流、系统压力和电流的设计值和测量值。这些数据在操作和维护手册（O&M手册）中都有说明。
2.4 Acceptable tolerances for all system parameters should be speci? ed prior to commencing the physical installation.
安装系统之前，应阐明所有系统参数的可接受公差。
2.5 Training should be provided to personnel after installation of the system, and should include how to perform operation and maintenance.
安装系统之后，应对人员进行包括如何进行系统操作和维护的知识在内的培训。
2.6 O & M manuals, schematic drawings, protocols and reports should be maintained as reference documents for any future changes and upgrades to the system.
应将O&M手册、系统图纸、方案和报告作为参考资料保存，以备将来的变更和系统更新使用。
2.7 Commissioning should be a precursor to system quali?cation and validation. 试运行应当先于系统确认和验证执行。 Quali?cation 资格
3.1 Manufacturers should qualify HVAC systems using a risk-based ap-proach. The basic concepts of quali?cation of HVAC systems are set out in Fig. 1 below. 制造商应当在风险评估的基础上对HVAC系统进行确认。HVAC系统确认的基本概念见图1。
3.2 The quali?cation of the HVAC system should be described in a validation master plan (VMP).
应使用验证主文件（VMP）说明HVAC系统的确认工作。
3.3 The validation master plan should de?ne the nature and extent of testing and the test procedures and protocols to be followed.
在验证主文件中，应当阐明试验的性质和试验执行的程度，且要说明需要遵循的试验程序和方案。
3.4 Stages of the quali?cation of the HVAC system should include de-sign quali?cation (DQ), installation quali?cation (IQ), operational quali? -cation (OQ), and performance quali? cation (PQ).
HVAC系统的确认程序应包括设计确认（DQ）、安装确认（IQ）、运行确认（OQ）和性能确认（PQ）。
3.5 Critical and non-critical parameters for all HVAC installation com-ponents, subsystems and controls should be determined by means of a risk analysis.
应以风险分析的方法，确定HVAC系统的所有安装部件、下游系统和控制装置的关键和非关键参数。
3.6 Any parameter that may affect the quality of the pharmaceutical product should be considered a critical parameter.
任何可能对药品质量构成影响的参数都应视作关键参数。
3.7 All critical parameters should be included in the quali? cation process. 应确认所有关键参数。 Figure 1 图 1
Quali?cation is a part of validation 确认是验证的组成部分
Note: A realistic approach to differentiating between critical and non-critical parameters is required, to avoid making the validation process unnecessarily complex. Example:
注：为了给验证过程减少不必要的赘余步骤，应建立可区分关键和非关键参数的现实方法。
例：
66 The humidity of the room where the product is exposed should be considered a critical parameter when a humidity-sensitive product is being manufactured. The humidity sensors and the humidity monitoring system should, therefore, be quali?ed. The heat transfer system, chemi-cal drier or steam humidi?er, which is producing the humidity-controlled air, is further removed from the product and may not require operational quali? cation.
如产品对湿度敏感，那么，与产品有接触的区域内的室内湿度也应视为关键参数。在这种情况下，湿度探测器和湿度监控系统都需要确认；而空气湿度控制装置，如热交换系统、化学干燥器或蒸汽增湿器，因为远离产品，因而也可以不必进行运行确认。
67 A room cleanliness classi? cation is a critical parameter and, therefore, the room air-change rates and high-ef?ciency particulate air (HEPA) ?lters should be critical parameters and require quali?cation. Items such as the fan generating the air?ow and the primary and second-ary ?lters are non-critical parameters, and may not require operational quali? cation.
考虑到室内洁净级别是一个关键参数，因此，室内的空气交换次数和高效空气过滤器（HEPA）都是需要确认的关键参数；而产生气流的风扇、一级和二级过滤器都不是关键参数，也不要求运行确认。
3.8 Non-critical systems and components should be subject to good engineering practice (GEP) and may not necessarily require full quali? cation.
对于不一定需要全面确认的非关键系统和部件，应遵守工程设计规范的要求。 3.9 A change control procedure should be followed when changes are planned to the HVAC system, its components, and controls, that may affect critical parameters. 计划对HVAC系统和该系统的部件、控制装置实施可能对关键参数构成影响的变更时，应遵循变更控制程序。
3.10 Acceptance criteria and limits should be de?ned during the design stage. 在设计阶段，应制定合格标准和限度。
3.11 The manufacturer should de?ne design conditions, normal operat-ing ranges, operating ranges, and alert and action limits.
制造商应说明设计条件、正常运行范围、运行范围、警戒和行动限度。 3.12 Design condition and normal operating ranges should be identi?ed and set to realistically achievable parameters.
应说明设计条件和正常运行范围，并将之设置成现实可行的参数。
3.13 All parameters should fall within the design condition range during system operational quali?cation. Conditions may go out of the design condition range during normal operating procedures but they should remain within the operating range. 在系统运行确认期间，所有参数都应在设计条件范围内。正常运行时，条件参数可能会超出条件的设计范围，但不超出运行范围。
3.14 Out-of-limit results (e.g. action limit deviations) should be recorded and form part of the batch manufacturing records.