Clean-up Phase and Recovery Time - is there a Difference?

自净时间和恢复时间 - 有什么不同？

With the new Annex 1 and the ISO 14644 series, detailed guidelines apply to the planning and GMP-compliant operation of cleanrooms and theirHVAC systems. Nevertheless, or precisely because of this, in practice there is often the question of the "recovery time" and the required "clean-up phase". Are these different requirements, or are they the same? Do they only apply to sterile or also to non-sterile medicinal products? Do they have to be measured in operation or at rest?

新版EU GMP附录 1 和 ISO 14644 系列有详细的指南适用于洁净室及其HVAC系统的规划和符合 GMP 的操作。然而，或者正因为如此，在实践中经常存在“恢复时间”和所需的“自净时间”的问题。他们是相同还是不同？它们仅适用于无菌药品吗？还是也适用于非无菌药品？它们必须在动态还是静态时进行测试？

Clean-up phase

自净时间

The determination of the clean-up phase is a requirement of Annex 1. It is defined as the time that elapses until the ventilation system has cleaned the particle concentration in the operating state "in operation" to the limit value of the particle concentration for the operating state "at rest". Consequently, the clean-up time is measured starting in the operating state "in operation" and ending in the operating state "at rest". The requirement is that the clean-up phase is less than 20 minutes.

自净时间是附录1的一项要求。它被定义为在空调系统将“动态”条件下的颗粒浓度自净到“静态”条件的颗粒浓度限度之前经过的时间。因此，从“动态”条件开始测量自净时间，以“静态”条件结束。要求自净时间少于 20 分钟。

Annex 1 applies to the production of sterile medicinal products, but can also be used for the production of other forms. This is also extremely sensible, as especially in the dusty production of e.g. solid dosage forms, the avoidance of cross-contamination during a product change is essential. Besides cleaning the manufacturing equipment, the premises and the air in the rooms must also be cleaned before a new product is produced. So it must be known how long the ventilation system needs to reach the clean (at rest) state again. The clean-up phase is determined for premises of cleanliness classes B, C and D (not for zone A) as well as in the non-sterile production areas, as far as reasonable (risk analysis or contamination control strategy).

附录1适用于无菌药品的生产，但也可用于其他形式的生产。这也是非常明智的，因为特别是在固体制剂等产尘操作中，避免切换产品期间的交叉污染至关重要。除了清洁制造设备外，在生产新产品之前，还必须清洁房间内的场所和空气。因此，必须知道通风系统需要多长时间才能再次达到洁净（静态）状态。B，C和D级洁净区（不适用于A级）以及非无菌生产区域的自净时间在应确定在合理范围内（风险分析或污染控制策略）。

So, in addition to cleaning validation, compliance with the clean-up phase after product changeover is part of the answer to a GMP inspector's question: "How do you prevent cross-contamination?". And it isalso helpful to know the answer in the production of non-sterile, solid dosage forms.

因此，除了清洁验证之外，产品切换后的自净时间符合性也是GMP检查员问题的一部分：“如何防止交叉污染？在生产非无菌固体制剂时也很有帮助。

Recovery time

恢复时间

The recovery time is a requirement of ISO 14644. The recovery time test is performed to determine whether the cleanroom is capable of returning to its specified cleanliness class within a limited period of time after brief exposure to a source of airborne particles. This test is not recommended for low-turbulence displacement flow (as for the clean-up phase, see above). The recovery time is thus measured in the state at rest, after an amount of particles has been added. The recovery time also provides information on the locking times in airlocks. It is therefore not only recommended for production rooms, but for all rooms with turbulent dilution flow. There is no normative requirement for a recovery time; each company is obliged to define a recovery time. Also, no time interval for measuring the recovery time is specified, but it is carried out during the initial qualification (classification) and is repeated in the event of a change in the room or the air change rate.

恢复时间是 ISO 14644 的要求。进行恢复时间测试是为了确定洁净室在短暂暴露于空气颗粒源后，是否能够在限定的时间内恢复到规定的洁净度等级。此测试不建议用于低湍流度的置换流（见上文，自净时间）。因此，在添加一定量的粒子后，在静态条件下测试恢复时间。恢复时间还提供有关气闸互锁时间的信息。因此，它不仅适用于生产车间，而且适用于所有具有湍流稀释流的房间。对恢复时间没有规范性要求；每家公司都有义务确定恢复时间。此外，没有规定测量恢复时间的时间间隔，但它是在初始确认（级别确认）期间进行的，并且在房间或换气次数发生变化时重新测定。

Since both measurements are completely different, measurements of both the recovery time and the clean-up phasehave to be carried out.

由于两种测量完全不同，因此必须同时进行恢复时间和自净时间的测量。