¡Manos a la masa!

4.1.2 Risk Mitigation 风险降低

Risk mitigation should be based on the level of risk tolerance determined during the risk assessment. Depending on the level of risk tolerance, mitigation efforts may include:

风险降低应基于在风险评估中确定的风险容忍度水平。根据不同的级别的风险容忍度,缓解措施可能包括：

• Pre-SIP and pre-use system integrity tests SIP 前和系统使用前完整性检测

• Additional monitoring points and biological indicators (if any) used during cycle development 程序开发期间额外监控点和使用的生物指示剂

• Additional safety factors built into the SIP cycle SIP 程序的额外安全系数

• Additional alarm points and/or control limits for temperature and pressure.

温度和压力的额外报警点和/或控制限

4.1.3 Cycle Development Data 周期开发数据

The amount of cycle development data needed to determine the key and critical parameter levels should be commensurate with the overall system risk. A high-risk system should have extensive data before proceeding to qualif ication; Other than routine commissioning tests, a low -risk system may need little or no cycle development data to proceed to qualification.

为确定关键和重要参数水平所需要的程序开发数据应该与整个系统的风险相称。在进行程序确认之前，高 风险的系统应该有大量的数据来确定参数;除了常规调试测试,一个低风险的系统可能需要很少或没有程序 开发数据就可以进行确认工作。

4.1.4 Testing 测试

Some routine tests that might be performed during cycle development:

在程序开发期间可进行一些常规测试

• Perform temperature mapping to determine cold and hot spots in the system.

进行温度分布测试以确定系统的冷点和热点

• Verify that excessive condensate is not building up at any points (e.g., low point drains, filter housings) in the system. The use of thermal imaging instruments can be used for this. Adjust/modify steam traps and system bleeds as necessary.

确认系统在任何点(如。排水口,过滤器外壳点)都不存在过度冷凝。使用热成像仪器可以用于此检测。

必要时调整/修改疏水阀和系统抽气装置。

• Verify that valve timing and sequence of operations are as described in the automation control systems ’ detailed design specification.

确认阀定时和操作顺序与自动化控制系统详细设计规范所述一致

• Determine time and temperature required to achieve an appropriate FP HYS value.

确定获得 FP HYS值所需的时间和温度

• Biological challenge, to ensure that an adequate F_BIO is achieved before proceeding to qualification of high-risk systems.

在对高风险系统进行确认前进行生物挑战测试，确保能获得足够的 FBIO

4.2 Cycle Parameter Determination 程序参数确定

Critical operating parameters for SIP cycles include time, temperature, and pressure. These parameters are manipulated to achieve the desired degree of sterilization or sanitization. Time, temperature, and pressure parameters should be determined for each phase of the SIP cycle (see Table 5.0-1 for typical cycle phases). Table 5.2-1 provides the operating procedure for each phase, as well as a brief description of the time, temperature, and pressure set points.

SIP 程序的关键操作参数包括时间、温度和压力。通过操纵这些参数来实现所需程度的灭菌或消毒。应该 确定 SIP 周期每个阶段的时间、温度、和压力参数 (见表 5.0 - 1 典型的周期阶段)。表 5.2 - 1 提供了操作过 程的每个阶段,以及一个简短的描述的时间,温度和压力设置点。

Table 5.2-1 also describes time, temperature, and pressure parameters for the optional System Integrity Test that may be performed before and/or after SIP of a system. Although there are several System Integrity Test methods (e.g., Pressure Hold, Mass Flow, and Tracer Gas), Table 5.2-1 only includes the most common System Integrity Test: the Pressure Hold Test.

表 5.2 - 1 还描述了可选系统 SIP 前和/后完整性检测的时间、温度、压力参数。虽然有几个系统完整性测试 方法(如压力保持、质量流量,示踪气体),表 5.2 - 1 只包括最常见的系统完整性测试:压力保持测试。

Table 5.2-1 Example of Typical SIP Cycle Operational Parameters

Pre-SIP System Integrity Test (optional) SIP 前完整性检测（可选）

Pressure

The system pressure is brought to a predetermined set point. All valves are shut off and the system is held for a predetermined amount of time. Pressure drop over that time is measured.

使系统压力达到预定的值。所有阀门都关闭,保压至一段时间。测量压力下降至一定水平所需要的时间

Time 时间

There are typically three time periods defined for a pressure hold test: pressurization time, stabilization time, and hold time. Each time period during a pressure hold test should be monitored and controlled.

通常有三个时间段定义压力保持测试:增压时间、稳定时间和保持时间。每个时间段都应该进行监控。

Pressurization Time is the time required to pressurize the system to the operating pressure for the pressure hold test. It is dependent on the volume of the system and the capacity (liters per minute at a given pressure drop) of the compressed gas supply. M ost procedures set an upper limit for pressurization time, as extended pressurization time may indicate a significant loss of system integrity.

增压时间是压力保持测试时对系统进行增压达到操作压力所需的时间。它是依赖于系统压缩气体供应的体积和容量(给定的压降下：升/分钟)。大多数程序设置一 个上限增压时间，因为延长加压时间可能表明系统完整性已遭到明显破坏。

Stabilization Time is a brief period—typically around 5 minutes—allowing the pressure within the system to equilibrate and any temperature increases due to pressurization of the system to stabilize.

稳定时间是一个短暂的时间，通常约 5 分钟，为系统内压力平衡时间，及由于系统增压后稳定系统引起温度上升。

Hold Time is defined by system size, system pressure, and the size of leak to be detected. Hold times should be minimized to avoid excessive temperature fluctuations.

保持时间是由系统大小、系统压力、检测到泄漏的大小决定的。保持时间应该最小化,以避免过度的温度波动

Temperature 温度

The system temperature is monitored (typically at ambient temperature) throughout the test to minimize false positives (“virtual leaks”) or false negatives caused by temperature fluctuations.

系统温度在整个测试过程中进行监测(通常在环境温度)以减少温度波动引起的假阳性(“虚拟泄漏”)或假阴性。

NOTE: Gay-Lussac’s Law: The pressure of a fixed amount of gas at a fixed volume is directly proportional to its temperature in degrees Kelvin. (P1/T1 = P2/T2).

注意：盖•吕萨克定律: 在固定的体积下，固定量的气体压力与开尔文温度成正比。(P 1 / T 1 = P 2 / T 2)。

When specifying the temperature for a pressure hold test, system characteristics such as jacketing, insulation, measuring instrument accuracy and ambient temperature of the surrounding area and the compressed gas supply should be considered.

当指定了压力保持测试的温度,应考虑系统特性如夹套、绝缘、测量仪器精度和环境温度和压缩气体供应。

Pressure 压力

The system is typically pressurized to a pressure less than or equal to the system pressure during the SIP cycle.

该系统通常是加压到压力小于或等于 SIP 期间系统压力。

The pressure hold period begins after pressurization and the system pressure is allowed to stabilize for a few minutes.

系统压力加压后开始压力保持期，允许压力稳定几分钟。

The allowable pressure loss during the pressure hold period is based on several factors including system volume, system design, and system criticality.

在压力保持期允许的压力损失是基于几个因素,包括系统体积、系统设计和系统重要程度。

Except during initial pressurization, system pressure is monitored, but not controlled.

除了在初始增压阶段外，其他时间应监测系统压力,而不用控制系统压力。

SIP Step SIP 步骤

Parameters 参数

Considerations 注意事项

Heat-Up/Air Displacement (Gravity Displacement or Vacuum/Steam Pulses) 加热/空气置换（重力置换或真空/蒸汽脉冲）

Gravity Displacement Method (typical Method used) 重力置换方法

（典型方法）

Procedure 程序

Steam is introduced into the high points of the system. Density differences cause the heated steam to displace trapped air in the system downward. Steam traps and constant bleeds at low points in the system allow the trapped air and condensate to exit.