ECA:欧盟附录1中，A级和B级的5 μ m粒子的限度要求

The 2022 EU GMP Annex 1 guideline is bringing some changes to cleanroom classification and monitoring, particularly about the 5µm particles in class A and B. This has led to a discussion within the industry regarding the interpretation and practical application of these requirements.
新版欧盟GMP指南附录1对洁净室分级和监测进行了一些更改，特别是关于A级和B级中的5 μ m粒子。这导致了行业内关于这些要求的解释和实际应用的讨论。

Classification vs. Monitoring 
分级与监测

Annex 1 differentiates between classification and monitoring for the 5 µm particles in class A and B. For cleanroom grades A, B, C, and D, the number of permissible particles correlates with room size, equipment, and personnel. These limits, derived from historical standards and current guidelines, are as follows:
附录1区分了A级和B级5µm粒子的分级和监测。对于A、B、C和D级洁净室的分级，允许的粒子数量与房间大小、设备和人员有关。这些限值源自于历史标准和现行指南，如下所示:

ISO 14644 states: Low 5 µm-values (> 5 µm are "macroparticles") - as 29 pcs - are for technical measurement reasons and statistically irrelevant and therefore - science and risk-based - cannot be the basis for a cleanroom classification.
ISO 14644规定:低5 μ m值(> 5 μ m是“大颗粒”)-例如29个-是出于技术测量原因，与统计无关，因此基于科学和风险，不能作为洁净室分类的基础。

"The occasional indication of macro particle counts, especially >= 5 µm, within grade A may be considered to be false counts due to electronic noise, stray light, coincidence loss etc. However, consecutive or regular counting of low levels may be indicative of a possible contamination event and should be investigated. Such events may indicate early failure of the room air supply filtration system, equipment failure, or may also be diagnostic of poor practices during machine set-up and routine operation."
“偶尔出现的大粒子，特别是>= 5µm，在A级区域内，可能被认为是由于电子噪声、杂散光、重合损失等原因造成的错误计数。然而，连续或周期性检测出较多 的小粒子可能表明可能发生污染事件，应进行调查。这些事件可能表明房间空气过滤系统的早期故障、设备故障，或者也可能是机器设置和日常操作过程中不良操作的诊断。”

Monitoring, however, demands continuous assessment to capture all interventions, transient events, and any system deterioration. The challenge lies in the volume of air to be monitored: While a cubic meter is the standard for classification, a cubic foot is often suggested for monitoring due to the practicality of existing equipment and the shorter measuring time.
然而，监测需要持续评估，以获知所有干预、瞬态事件和任何系统恶化。挑战在于要监测的空气体积：虽然立方米是分类的标准，但由于现有设备的实用性和较短的测量时间，通常建议监测立方英尺。

The 1 (one) Particle Alarm Dilemma

1个粒子报警的困境

When shifting the limit from cubic meter to cubic foot for 5µm particles, a single particle detection triggers an alarm. This essentially suggests a requirement for the absenceof any >= 5 µm particles. One approach to this stringent requirement is to study historical trends and adjust the limits: Increasing the 5µm particle limit above one and decreasing the 0.5µm particle limit below 100.

Historical Context and the FED 209D Specification

历史背景和FED 209D标准

Historical cleanroom standards, such as FED 209D, offer valuable insights.
历史上的洁净室标准，如FED 209D，提供了有价值的见解。

Continuous Monitoring Strategies

持续监测策略

Continuous monitoring does not imply continuous data but rather consistent sampling. Strategies to address the 1 particle/ft³ alarm include:

• 1. Extended Sampling Periods: Taking samples longer than one minute to reduce the multiplication factor.

  延长采样周期:采样时间超过一分钟，以减少乘法系数。

• 2. Rolling Averages: Responding based on a rolling average of several minutes' data.

  滚动平均值:基于几分钟数据的滚动平均值进行响应。

• 3. Frequent Short Samples: Taking shorter samples but averaging over time to mitigate false alarms.

  频繁的短样本:取较短的样本，但随着时间的推移取平均值，以减少误报。

• 4. Rate of Occurrence: Focusing on the frequency of particle counts rather than single instances, akin to viable particle monitoring in USP 1116.

  发生率:关注粒子计数的频率，而不是单个实例，类似于USP 1116中的浮游菌监测。

Conclusion 结论

The revised Annex 1 guidelines emphasizes the monitoring of >= 5µm particles, necessitating practical and scientifically sound approaches to compliance.
修订后的附录1强调监测>= 5 μ m颗粒，需要采取切实可行且科学合理的合规方法。