法规解读| ECA《GMP/GDP问答指南》3.0版发布：灯检与可见异物检查

2026年9月，ECA Academy正式发布《The GMP/GDP Questions & Answers Guide》Version 3.0。这份指南以问答形式汇集了GMP/GDP实践中的常见疑难问题，覆盖从生产、质量到供应链的多个合规领域，是制药行业应对法规解读差异的重要参考。

 

在最新版中，第6.1节“Questions and Answers on Visual Inspections”专门聚焦注射剂灯检与可见异物检查，内容涵盖人工检查、自动检查、确认/验证/再确认、测试集、AQL测试、缺陷分类、特殊产品、监管事务以及过程控制/SPC，几乎覆盖了灯检合规的全部关键环节，值得药企灯检相关岗位重点关注！

 

本文将中英文对照整理如下，中文翻译忠于原文，供行业同仁参考。如需了解更详细的法规解读，请联系我们。

 

 

 

 

 

 

 

 

 

 

 

 

 

6.1 Questions and Answers on Visual Inspections/关于视觉检查的问答

MI1 According to Annex 1 of the EU-GMP-Guideline, operators doing the inspection for particles and other defects should make frequent breaks from inspection. Are there any regulations concerning rest times and time intervals? 

根据欧盟-GMP-指南附录 1，检查颗粒物和其他缺陷的操作员应经常中断检查。是否有关于休息时间和时间间隔的规定？

An interpretation of this requirement is not trivial. Sometimes, the companies interpret it in a significantly different way. In practice, for example, the following variants can be found: 

对这一要求的解释并非微不足道。有时，公司会以截然不同的方式解释它。例如，在实践中，可以发现以下情况：

• 55 minutes inspecting, 5 minutes break over a period of 8 hours/ 检查55分钟，休息5分钟，共8小时

• 20 minutes inspecting, 20 minutes other activities over a period of 8 hours/ 检查20分钟，20分钟其他活动，共8小时

• 20 minutes inspecting, 5 minutes break over a period of 4 hours/ 检查20分钟，休息5分钟，共4小时

It is a known fact that this activity normally can be carried out successfully for a maximum period of 15 to 20 minutes. Insofar the provision "55 minutes inspecting, 5 minutes break over a period of 8 hours" doesn't seem to be appropriate. Ideally, the activity of inspection will be limited to 15 to 20 minutes. Afterwards a break for the eyes should be taken without carrying out any other activities. 

众所周知，这项活动通常可以成功进行最长 15 至 20 分钟。就此而言，“检查55分钟，休息5分钟，共8小时” 的规定似乎不太合适。理想情况下，检查活动应限制在 15 至 20 分钟内。之后应该进行眼部休息，而不进行任何其他活动。

MI2 Which requirements should there be concerning the requalification of the personnel carrying out the optical inspection? Are there specific time intervals to be observed and should the requalification be announced? 

MI2 关于进行光学检查的人员资格再认证应有哪些要求？是否需要遵守特定的时间间隔，以及是否应该宣布资格再认证？

The pharmaceutical companies have different approaches concerning the time intervals for requalification. The intervals reach from each month to every two years. Every two years certainly is too long. This period of time is especially problematic if the person carrying out the inspections doesn't pass the requalification any more. Which consequences does this have for the batches inspected by this operator? Insofar it seems to be appropriate to choose a time interval that is as short as possible and to control the personnel for example by means of an AQL testing. Are test sets used in the context of the requalification this should not be announced before the qualification run. For this reason, it is advisable to requalify not exactly every six/twelve months, for example, but to do this on a random basis i.e. to lay down irregular time intervals. If test kits are processed in the context of requalification you need to think carefully about the question whether the test kits should be inspected directly in the morning or at the end of the day in the case of an eight-hour shift. Naturally, it is advisable to choose the worst case situation and therefore, to let the inspection be carried out at the end of the shift. 

制药公司对再资格认证的时间间隔有不同的方法。间隔从每月到每两年不等。每两年肯定太长了。如果进行检查的人不再能通过再资格认证，这段时间尤其成问题。这对该操作员检查的批次有什么影响？目前，似乎应该选择尽可能短的时间间隔，并通过 AQL 测试来控制人员。测试集是在再资格认证背景下使用的，这一点在资格认证开始之前不应公布。基于这个原因，建议不要每六个月或十二个月进行一次再资格认证，而是应该随机进行，即设定不规则的时间间隔。如果测试工具包是在再培训的背景下处理的，你需要仔细考虑是应该在早上直接检查测试工具包，还是在 8 小时轮班的情况下在一天结束时进行检查。当然，最好选择最糟糕的情况，因此，应该在轮班结束时进行检查。

MI3 How often have employees of the manual (or semi-automatic) inspection to be trained? What does "regularly" mean in this context? 

MI3 手动 (或半自动) 检查的员工多久需要接受一次培训？在这种情况下，“定期” 是什么意思？

With regard to visual inspection, the difference between initial qualification and requalification must basically be made. Strictly speaking, requalification is an examination of the status of a person's qualification. It is recommended to re-qualify employees at least every 12 months. 

在目视检查方面，基本上必须区分初始资格认证和再资格认证。严格来说，再资格认证是对一个人资格状态的检查。建议至少每 12 个月对员工进行一次再资格检查。

MI4 Should the set of samples for the qualification (training) of the staff be taken directly form the production rejects or should it be produced artificially based on typical defects? 

MI4 员工资格认证 (培训) 的样本集是应该直接从生产废料中提取，还是应该根据典型缺陷人工生产？

Usually, the training set should be taken directly from the production rejects. Unfortunately, some failures occur only very rarely so that you have to produce some of them yourself. Finally, you have a set with failures that are typical for the production that has to undergo a formal release procedure described in an SOP. This guarantees that the failures are typical and that you can use them for training. 

通常，训练集应该直接从生产剔除中获取。不幸的是，一些故障很少发生，因此你必须自己生产其中一些。最后，你有一组典型的生产故障，这些故障必须经过 SOP 中描述的正式发布程序。这确保了这些故障是典型的，你可以将它们用于训练。

MI5 Are there empirical values about how long do lamps in semi-automatic testing stations keep their intensity? 

MI5 关于半自动测试站中灯光保持亮度的持续时间，是否存在经验值？

Here, the certificates of the lamp manufacturers should be consulted. Usually, 2-3 years are indicated. In many companies, the lamps are exchanged routinely after one year to never have to question the test results due to possible lamp weakness retrospectively. 

在这里，应参考灯具制造商的证书。通常标明 2-3 年。在许多公司，灯具在一年后会定期更换，这样就不必因为可能存在的灯具弱点而对测试结果提出质疑。

MI6 We have trained our inspection team to inspect containers in less than 5 seconds against a white and black background. Moreover we do an AQL testing afterwards and if the AQL fails the qualification status of the inspector will also be evaluated within a deviation. So is it allowed so shorten the inspection time? 

MI6 我们已经训练我们的检查团队在黑白背景下，在不到 5 秒的时间内检查容器。此外，我们事后会进行AQL 测试，如果 AQL 未通过，检查员的资格状态也会在偏差范围内进行评估。因此，是否允许缩短检查时间？

Ph.Eur. and USP requirements for particulates are clear – manual visual inspection for 5 sec in front of black and white background is required. Annex 1* of the GMP guidance document states to use a given time and given set-up for inspection. Any modification must be validated and should show to be equal or better than the compendial approach. *(Vs. 2008 rev.) 

Ph.Eur.和 USP 对颗粒物的要求很明确——需要在黑白背景前进行 5 秒的手动目视检查。GMP 指南文件的附件 1* 规定使用给定的时间和设置进行检查。任何修改都必须经过验证，并且应该显示等于或优于药典方法。*(Vs. 2008 rev.)

MI7 According to Ph.Eur the light intensity should be between 2000-3750 Lux but according to USP 790 it should be minimum 2000-3750 Lux. Is it ok then that the light intensity is higher than 3750 Lux? 

MI7 根据 Ph.Eur，光强应在 2000-3750 勒克斯之间，但根据 USP 790，应至少为 2000-3750 勒克思。那么，光强高于 3750 勒克斯可以吗？

The “minimum intensity” in USP <790> refers to 2000 Lux. But higher intensities as 3750 Lux or higher are possible and acceptable for certain types of products (e.g. Blow-Fill-Seal container). But operators fatigue will be higher and you have to adopt the eye breaks and the inspection time per day accordingly. 

USP <790>中的 “最小强度” 指的是 2000 勒克斯。但对于某些类型的产品 (例如BFS容器)，可以接受更高的强度，如 3750 勒克斯或更高。但操作员的疲劳程度会更高，你必须每天采取适当的休息时间和检查时间。

MI8 Is the wearing of anti reflective eyewear by manual inspectors a common practice among pharmaceutical companies during Manual or Semi automatic inspection as a measure against fatigue? 

MI8 手动检查员佩戴防反射眼镜是否是制药公司在手动或半自动检查期间常见的做法，以防止疲劳？

Wearing anti reflective eyewear is not the way for improving the quality of the visual inspection. On one hand a high light intensity can be necessary, on the other hand the tiring of the human eye seems to work contra productive to the detecting of the defects. One has to find a way between both effects meaning: use more eye breaks when using light with a higher intensity. 

佩戴防反射眼镜并不是提高视觉检查质量的方法。一方面，高强度的光线可能是必要的，另一方面，人眼的疲劳似乎会对缺陷的检测产生不利影响。人们必须在这两种影响之间找到一种平衡：在使用更高强度的光线时，需要更多的眼部休息时间。

MI9 Is there a requirement in regards to the size of the visual inspection booth, e.g. width, length, etc? 

MI9 是否对视觉检查隔间的尺寸有要求，例如宽度、长度等？

No 无

MI10 How can foreign particulate matter be distinguished from a micro bubble in a vial that can form during vial stirring during manual inspection? 

MI10 如何区分异物颗粒物质与西林瓶中的微小气泡？这些气泡可能是在手动检查过程中西林瓶搅拌时形成的。

Up to now there are limited technologies for distinguishing air bubbles and real particles. Cameras and the human eye cannot see a difference when the particles/air bubbles are small. The only way is to avoid air bubbles. One approach is the use of two cameras. In case particle-camera1 detects something but particle-camera2 (under the same conditions as camera1) does not, it is likely an air bubble. 

到目前为止，区分气泡和真实粒子的技术还很有限。当粒子/气泡很小时，相机和人眼都无法看出区别。唯一的方法是避免使用气泡。一种方法是使用两台相机。如果粒子相机 1 探测到了某些东西，而粒子相机 2(在与相机1相同条件下) 却没有，那么它很可能是一个气泡。

MI11 What exactly is meant by point 2.1 of the best practice paper ("The relative humidity and air velocity should be controlled and ensure comfortable working conditions.")? Is a permanent room monitoring required? 

MI11 最佳实践论文第 2.1 条 (“应控制相对湿度和空气流速，确保舒适的工作条件”) 究竟是什么意思？是否需要永久性房间监控？

It is a fundamental GMP requirement: the fulfilment of a requirement has to documented. A permanent monitoring of temperature and humidity may not be necessary, but how to prove during an inspection, that the working conditions for the human inspectors have been adequate? This will not be possible without measuring temperature and humidity and some sort of system, meaning the documentation and evaluation of measuring data. If this is not part of the building control system anyway, a manual system may also be possible. 

这是一个基本的 GMP 要求：满足要求必须进行记录。对温度和湿度的永久监测可能不是必要的，但如何在检查过程中证明人工检查员的工作条件已经足够？如果没有测量温度和湿度以及某种系统，这将是不可能的，这意味着要对测量数据进行记录和评估。如果这不是建筑物控制系统的一部分，那么手动系统也是可能的。

AV1 The grey portion of fully automatic control is often checked manually, to return not clearly or fully tested products back to the inspection process. Is it allowed to carry out this testing with the automated inspection machine? 

自动化检查AV1 全自动控制的灰色部分通常需要手动检查，以便将未经清晰或完全测试的产品退回检查过程。是否允许使用自动化检查机器进行这项测试？

From a GMP view, there are no restrictions. It is also important here that at the end a yield calculation and evaluation in the batch record appears. And there are also automated inspection systems that have already integrated the double inspection with multiple cameras. 

从 GMP 的角度来看，没有任何限制。在这里，最终在批次记录中出现产量计算和评估也很重要。此外，还有自动化检查系统，它已经将双重检查与多个摄像头整合在一起。

AV2 Can one reject test be considered as a good after two "good" inspection on the same machine? 

AV2 在同一台机器上进行两次 “良好” 检测后，一次剔除测试是否可以被视为良好？

This is possible in a few cases where - for example - the machine stopped and goods were therefore ejected. Otherwise, "reject" should always remain "reject". This is particularly applicable to "bad" goods which have been rejected because of particles or opacity. Containers sorted out due to cosmetic defects are however usually being re-inspected. 

这在少数情况下是可能的，例如，机器停止工作，商品因此被排出。否则，“剔除” 应始终保持 “剔除”。这尤其适用于因颗粒物或不透明度而被剔除的 “劣质” 商品。然而，由于外观缺陷而被分类的容器通常会被重新检查。

AV3 We produce a lot of products with different formats. Until now we use a rejection rate of <2% as acceptance criterion and sets of samples from production to control the functionality of the machine. 

AV3 我们生产许多不同规格的产品。迄今为止，我们使用小于2% 的剔除率作为验收标准，并使用生产中的样品集来控制机器的功能。

An AQL test should be carried out for each batch. In the meantime this is expected by the authorities and inspectors. This is also described in the ECA Good Practice Guide on Visual Inspection. A control of the rejection rate of the 100% inspection is also expected but it rather serves for recognizing whether a batch differs from the normal unobtrusive production. This trending limits should be product specific. A generic limit eg <2% would need a rationale. 

应对每个批次进行 AQL 测试。与此同时，这是监管当局和检查人员的期望。这也在 ECA 视觉检查良好实践指南中有所描述。还应控制 100% 检查的剔除率，但它更多地用于识别一个批次是否与正常的、不引人注目的生产不同。这种趋势性限值应该是产品特定的。通用限值例如<2% 将需要一个合理的解释。

AV4 In highly automated manufacturing lines for LVP flexible containers, the visual inspection process may/cannot comply to the standard visual inspection criteria e.g.: 5 sec inspection time, agitation of the container etc. Is this a compliance problem? 

AV4 在 LVP 柔性容器的高度自动化生产线中，视觉检查过程可能/不能符合标准的视觉检查标准，例如:5 秒钟的检查时间、容器的搅拌等。这是否是一个合规性问题？

The requirements like 5 sec inspection time required by pharmacopoeias are addressing manually performed visual inspection. If the visual inspection is performed automatically, it is the company’s responsibility to ensure that the inspection via camera systems is as effective as a manual visual inspection via a validation (e.g. Knapp Test). 

药典所要求的 5 秒钟检查时间等要求，是为了解决手动进行的视觉检查问题。如果视觉检查是自动进行的，公司有责任确保通过摄像头系统进行的检查与通过验证进行的手动视觉检查一样有效 (例如，Knapp测试)。

AV5 Do we have to perform challenge test before production / shift to check the 100% automatic visual inspection? And how often? 

AV5 我们是否必须在生产/换班前进行挑战性测试，以检查 100% 自动化的视觉检查？频率如何？

A function test kit (system suitability test kit) used before and after the inspection of each batch to demonstrate the functionality of the fully automated inspection system. It may contain an abridged set of more apparent defects such as big particles, cracked or empty containers. 

一个功能测试工具包 (系统适用性测试工具包)，用于在每批检查前后展示完全自动化检查系统的功能。它可能包含一组更明显的缺陷，如大颗粒、裂缝或空容器。

QV1 In the course of validation and during operation there are recurring problems with false reject rates in the case of fully automated systems. Are there any GMP requirements concerning this? 

QV1 在验证过程和运行过程中，对于完全自动化的系统，存在反复出现的错误剔除率问题。是否存在与此相关的GMP 要求？

Due to the fact that the systems are able to detect also considerably smaller particles than human operators there are repeatedly emerging more or less big amounts of objects in the part with defects that have been assessed by a human operator as being good. Furthermore, a fully automated system might also get problems with air bubbles and reject these objects as having defects. In the end, the trick is to configure the system in such a way that no objects containing very small particles are rejected. In some companies the objects rejected by automated systems are again inspected by human operators. But this method entails the risk that objects actually having defects are suddenly classified as having no defects by the human operator. Two conclusions can be drawn from the point of view of GMP. Rejecting objects without defect does not entail a risk for patients and thus seems to be practicable. On the other hand one could also criticise the qualification as such since a system making errors is not sufficiently qualified. In any case, acceptance criteria should be defined for the part with defects. In the case of exceedance certain measures are to be taken such as an additional 100 % inspection for example. To sum it up: there is no requirement to set a limit for false rejects. But on the other hand it is advisable to also set a limit for the false rejects, usually during the qualification/5000 test. Because having no limit or a very high number of false rejects may question the whole qualification during a GMP inspection. 

由于系统能够检测到比人类操作员更小的颗粒，因此在存在缺陷的部分会反复出现或多或少大量被人类操作员评估为良好的物体。此外，一个完全自动化的系统也可能会出现气泡问题，并将这些物体剔除，认为它们存在缺陷。最后，诀窍在于配置系统，使其不会排除任何含有非常小颗粒的物体。在一些公司，被自动化系统剔除的物体再次由人类操作员进行检查。但这种方法带来的风险是，实际上存在缺陷的物体可能会突然被人类操作员归类为没有缺陷。从 GMP 的角度可以得出两个结论。剔除没有缺陷的物体不会给患者带来风险，因此似乎是可行的。另一方面，人们也可以批评这种做法的合格性，因为一个会出错的系统是不够合格的。在任何情况下，都应该为存在缺陷的部件定义验收标准。在超过标准的情况下，应该采取一些措施，例如额外的 100% 检查。总结一下：没有要求为假剔除设定限值。但另一方面，建议也为假剔除设定限值，通常在确认/5000 测试期间。因为如果没有限值或假剔除数量过高，可能会在 GMP 检查期间质疑整个确认。

QV2 We have about 50 different aqueous solutions for a few hundred products (one solution for several formats). So far we have prepared one set of samples (function set, qualification set including Knapp set) from production rejects. This is very time consuming. Do you think it might be useful to measure parameters such as viscosity, surface tension of the 50 solutions in order to group the products (bracketing)? 

QV2 我们有大约 50 种不同的水溶液，适用于几百种产品 (一种溶液适用于多种规格)。到目前为止，我们已经从生产废弃物中制备了一组样本 (功能集、确认集，包括Knap 集)。这非常耗时。你认为测量 50 种溶液的粘度、表面张力等参数是否有用，以便对产品进行分组 (括号法)?

Bracketing is useful here. The rationale using viscosity is ok. 

括号法在这里是有用的。使用粘性的理由是可以的。

QV3 Which statistical tests should be applied to demonstrate equivalence of different visual inspection processes (e.g. manual versus automatic inspection process)? 

QV3 应该应用哪些统计测试来证明不同视觉检查过程 (例如，手动检查过程与自动检查过程) 的等效性？

The goal of the AIM qualification is to show that the machine is equal or better than the “gold standard” that is the human inspection. This can be done by comparing the overall detection rates for particles (this set also includes non-particle objects) and at least 10 inspections runs of this set for manual inspection (normally 3 operators) and the same set of objects on the machine. For non-particle defects (scratches, missing stopper,…) one could use a predefined limit or also a man/machine comparison. 

AIM 确认的目标是证明机器等同于或优于人工检查的 “黄金标准”。这可以通过比较粒子的整体检测率 (这个集合也包括非粒子物体) 和至少 10 次人工检查 (通常是 3 名操作员) 以及机器上相同的物体集合来实现。对于非粒子缺陷 (划痕、缺失的胶塞等)，可以使用预定义的限值，也可以使用人机比较。

TS1 What are the differences between qualification, particle (Knapp test) and function test set?/ 确认测试集、粒子(Knapp 检验)测试集和功能测试集之间有什么区别？

The function test set serves for a sort of system suitability test, i.e. this test is used to test before and after each batch whether the cameras are functioning correctly. Usually, no challenging samples are used for this, but rather unities with particles having a detection rate of 100% such as particles with a size of 1000 µm, vials with missing stoppers. 

功能测试集用于一种系统适用性测试，即在每批次前后用于测试相机是否正常工作。通常，不使用具有挑战性的样品，而是使用检测率为 100% 的颗粒单元，例如尺寸为 1000μm 的颗粒、缺少胶塞的西林瓶。

Qualification test set: the qualification test set consists of product specific containers containing the product and having all known "static" defects (scratches, wrong flip-off, missing stopper,...). Usually, about 10-20% of the containers of the set have a defect. New failures or defects are added to the qualification test set. 

确认测试集：确认测试集由包含产品的特定产品容器组成，这些容器具有所有已知的 “静态” 缺陷 (刮痕、错误的折叠、胶塞缺失等)。通常，集合中约 10-20% 的容器存在缺陷。新的故障或缺陷会被添加到确认测试集中。

Particle test set (Knapp-Test): Sets that contain only particles. These are particles having the size from 50µm to 1000µm and consisting of different materials (plastic, the material stoppers are made of, glass, metal). Hence, they are "non-static", i.e. the defect is in the container or in the drug solution. Particle test sets are part of the qualification test set at the same time. 

颗粒测试集 (Knapp-Test):仅包含颗粒的集合。这些是直径在 50μm 至 1000μm 之间的颗粒，由不同材料 (胶塞材质塑料、玻璃、金属) 组成。因此，它们是 “非静态” 的，即缺陷存在于容器或药物溶液中。颗粒测试集同时也是确认测试集的一部分。

TS2 Should all these test sets be prepared artificially? Should this be done, for instance, by an external laboratory with defined failures?/ 是否应该由人工制备所有这些测试集？例如，是否应该由一个具有明确失败样品的外部实验室来制备？

We prepare the static defects in-house and a part of the non-static defects (particle defects) are produced externally. But it is also possible to have everything produced externally. But the static defects should be the same that are generated in the worst case by your production machines. Therefore, I advise to make these in-house and get the release from QA. In this way you would have representative bad samples from your process. In the best case you take bad samples from your process but it is not possible to do this for all samples. 

我们在内部制备静态缺陷，一部分非静态缺陷 (粒子缺陷) 是在外部生产的。但也可以让所有东西都在外部生产。但静态缺陷应该与你的生产机器在最坏情况下产生的相同。因此，我建议在内部制造这些缺陷，并从 QA 获得放行。这样，你就会从你的工艺中获得具有代表性的不良样品。在最好的情况下，你可以从你的工艺中获得不良样品，但不可能对所有样品都这样做。

TS3 The problem is that sets of samples have to be remade regularly since they have expired. How do you prepare the function test set?/ 问题在于，样品集因为已经过期而必须定期重新制造。如何准备功能测试集？

Usually, our sets keep several years. Single samples have to be replaced again and again. These single samples are then released by QA and we introduce them into the set. The sets should be controlled at least once a year and be released again afterwards. 

通常，我们的样本集会保持几年。单个样本必须反复更换。然后，QA 会放行这些单个样本，我们将其引入样本集。样本集应该至少每年控制一次，之后再次被放行。

TS4 How long can a training kit be used? / 培训套件可以使用多长时间？

Training kits should contain all kind of defects and must be updated constantly with new evolving defects out of production. Expiry of specific defects depends on nature (a crack will not expire; small particles may clot together…). The set must be regularly released and reinspected by a supervisor. 

培训套件应包含各种缺陷，并且必须不断更新生产过程中出现的新缺陷。特定缺陷的有效期取决于其性质(裂缝不会过期；小颗粒可能会凝结在一起......)。套件必须定期放行，并由主管重新检查。

TS5 How should qualification sets be prepared for a new product?/ 如何为新产品准备确认测试集？

All representative defects coming from a production line should be included in the set. Some of the defects need to be generated but if possible should be taken from production. These defects need to be classified. See chapter 5 of the Best Practice Guide.

应该将来自生产线的所有代表性缺陷都包括在确认测试集中。一些缺陷需要产生，但如果可能的话，应该从生产中采集。这些缺陷需要进行分类。请参阅《最佳实践指南》第 5 章。

RQ1 If systems for the fully automatic visual inspection are used, regular functional testing is carried out. Must the system be requalified nevertheless? 

RQ1 如果使用全自动视觉检查系统，则会进行常规功能测试。尽管如此，系统是否仍需要重新确认？

According to EU-GMP a difference must be made between the following activities in the case of a fully automated system: 

根据欧盟-GMP 规定，在完全自动化系统的情况下，必须对以下活动进行区分：

• Qualification: in the case of new equipment/ 确认：在新设备的情况下

• Requalification: Assessment of equipment within defined time intervals/ 再确认：在规定的时间间隔内对设备进行评估

• Periodic evaluation: According to EU-GMP Annex 11./定期评估：根据 EU-GMP 附件 11。

Functional testing addresses the sensor functionality only and is typically carried out before and after batch inspection. Due to its limited scope, functional testing cannot replace requalification of an equipment. Requalification should be performed according to the EU-GMP Annex 15 to safeguard that the whole equipment remains in a state of control. Requalification programs and intervals shall be planned and justified according to the guideline. In the context of the assessment of the facility, the functional testing carried out until the date of requalification will certainly be part of the assessment. 

功能测试仅涉及传感器功能，通常在批次检查之前和之后进行。由于其范围有限，功能测试不能替代设备的再确认。设备再确认应按照 EU-GMP 附件 15 进行，以确保整个设备保持在控制状态。再确认计划和间隔应根据指南进行规划和证明。在设施评估的背景下，直到再确认日期为止进行的功能测试必然是评估的一部分。

RQ2 Requalification: If the regular requalification of the automatic inspection machine is carried out by means of the test of 5,000 does this mean that the 5,000 vials from one production batch must all be controlled manually and by the automatic inspection machine? 

RQ2 再确认：如果自动检测机器的常规再确认是通过5000 个测试进行的，这是否意味着一个生产批次中的5000 个西林瓶都必须由自动检测机器手动控制？

I.e. is it necessary to repeat the man-machine-comparison that was carried out in PQ? Almost correct. PQ consists of the particle (Knapp test) run, the run concerning the "static" defects and also of a run of 5,000 of GOOD vials. This run of 5,000 is carried out once a year for each product. The Knapp test and the "static" test are not repeated except when there have been changes at the particle detection stations. Without changes (something that occurs only very seldom) only the test of 5,000 is carried out, i.e. 5,000 vials from the automatic inspection machine are inspected by a person and by the machine 

也就是说，是否有必要重复在 PQ 中进行的人机对比？几乎正确。PQ 包括颗粒 (Knapp 测试) 运行、关于 “静态” 缺陷的运行，以及 5,000 个 GOOD 西林瓶的运行。这 5,000 个西林瓶每年对每个产品进行一次。除非颗粒检测站发生变化，否则不会重复 Knapp 测试和 “静态” 测试。如果没有变化 (这种情况很少发生)，只会进行 5,000 个西林瓶的测试，即 5,000 个来自自动检测机器的西林瓶由一个人和机器检查。

AQ1 Is AQL testing mandatory as a part of the visual inspection? 

AQ1 AQL 检测是否作为视觉检查的一部分是强制性的？

A direct requirement cannot be derived from the EU GMP. Yet, the AQL tests correspond to the state of the art in science and technology. Since we know that neither a manual nor an automated visual inspection can guarantee a 100% particle-free batch, an additional measure - like the AQL tests - is certainly appropriate. Another method would be of course a second 100% inspection. Or you could show in the validation that the test method used is a 100% flawless and complete, what will hardly be possible in practice. For US, the AQL testing has been included in the USP, chapter <790>. 

直接要求不能从欧盟 GMP 中得到。然而，AQL 测试对应于科学技术的现状。由于我们知道，无论是手动还是自动视觉检查都不能保证 100% 无颗粒的批次，因此额外的措施——例如 AQL 测试——当然是合适的。另一种方法当然是第二次 100% 检查。或者，你可以在验证中证明所使用的测试方法是 100% 无缺陷和完整的，这在实践中几乎是不可能的。对于美国，AQL 测试已包含在 USP 中，第<790>章。

AQ2 Do the European agencies follow the rules for AQL testing given in USP <790>? 

AQ2 欧洲机构是否遵守 USP <790>中规定的 AQL 测试规则？

There is no written guidance in Europe requiring an AQL test according USP <790>. Companies have to define their own way to implement a check of the visual inspection efficacy. 

欧洲没有书面指南要求根据 USP <790>进行 AQL 测试。企业必须自行定义实施视觉检查有效性检查的方式。

AQ3 Should the AQL be inspected by QC or production 

AQ3 AQL 是否应由质量控制中心或生产部门进行检查

AQL manual inspection may be carried out by production staff (to avoid setting up a separate visual inspection team in QC) under a quality oversight or the quality unit. If performed by production operators, the AQL test should not be done by members of the team that was performing the 100 % visual inspection of the batch. 

AQL 手动检查可由生产人员在质量监督或质量单元下进行 (以避免在质量控制中心设立单独的目视检查团队)。如果由生产操作员进行，AQL 测试不应由对批次进行 100% 目视检查的团队成员进行。

AQ4 Is the AQL acceptance criteria of 0.65 for the particles only or for the overall defects? 

AQ4 AQL 验收标准0.65是仅针对颗粒还是针对整体缺陷？

USP <790> addresses visual inspection for particles. So the requirement to apply an AQL of 0.65 or sample plans with better protection applies to particles. Other defects like cracks or stopper failures may be addressed with tighter AQLs. 

USP <790> 解决粒子的目视检查问题。因此，对粒子应用 0.65 AQL 或采样方案以获得更好的保护的要求适用于粒子。其他缺陷，如裂缝或胶塞失败，可以通过更严格的 AQL 来解决。

AQ5 Which sample size should be taken if various AQL-levels depending on the defect criticality are used (for example batch size of 22.000, AQL = 0 for critical defects, AQL = 0.65 for major defects, AQL = 2.0 for minor defects) 

AQ5 如果根据缺陷严重程度使用不同的 AQL 水平 (例如，批次大小为 22,000,AQL = 0 用于严重缺陷，AQL = 0.65 用于主要缺陷，AQL = 2.0 用于次要缺陷)，则应采用哪种样本大小？

There is a misunderstanding. The sample size is depending on the Quality Level one wants to use (e.g. level II). With this level and the batch size one gets the size of the sample which must be drawn. The AQL level (e.g. 0.65) then defines how many defects are allowed to accept the defined batch quality. Of course the AQL level then depends on the criticality because the more critical the less defects are allowed to be found in the AQL procedure. 

这里存在一个误解。样本大小取决于一个人想要使用的质量等级 (例如 II 级)。使用这个等级和批次大小，一个人可以获得必须绘制的样本大小。AQL 等级 (例如 0.65) 随后定义了允许接受定义的批次质量的缺陷数量。当然，AQL 等级随后取决于严重缺陷，因为严重缺陷越高，在 AQL 过程中允许发现的缺陷就越少。

AQ6 For vials packaged in separated sub-batches, when the 100% visual inspection is located at the beginning of the packaging process, should the acceptance sampling be statistically significant on the full manufacturing batch or on each single sub-batch? 

AQ6 对于分批包装的西林瓶，当100% 目视检查位于包装过程的开始阶段时，接受抽样应该在整个制造批次还是在每个单独的子批次上具有统计学显著性？

The AQL sampling should be based on the sub-batch meaning the batch size that is inspected. One is checking with this test if the incoming quality of the batch is according the quality which is expected. The levels do not need to be the same like for the initial batch. 

AQL 采样应基于子批次，即所检查的批次大小。其中一个测试是检查批次的输入质量是否符合预期质量。水平不必与初始批次相同。

DC1 The USP in sections 790 and 1790 classifies glass defects as a major defect. There are many types of glass defects, e.g. glass particulates adhered to the side of the vial, and loose glass within a vial (in both incidents if product integrity/sterility assurance is not compromised), could you please tell me what the defect classification levels (critical, major or minor), for either of the former mentioned defects should be. 

DC1 USP 在第 790 和 1790 节中将玻璃缺陷归类为主要缺陷。玻璃缺陷有多种类型，例如粘附在西林瓶侧面的玻璃颗粒，以及西林瓶内松散的玻璃(在这两种情况下，如果产品完整性/无菌性保证没有受到影响)，您能否告诉我，对于前面提到的任何一种缺陷，缺陷分类等级应该是什么 (严重、主要还是次要)?

Both USP chapters do not make any classification of defects. This needs to be done by the pharmaceutical company and has to be based on a quality risk assessment 

USP 的两个章节都没有对缺陷进行任何分类。这需要由制药公司完成，并且必须基于质量风险评估。

DC2 How should freeze-drying defects such as collapse and melt-back be classified regarding to their criticality 

DC2 如何根据冻干缺陷的严重程度对塌陷和熔回等缺陷进行分类

In the scientific literature a melt-back is seen to be critical. The difference of a collapsed and a melt back is difficult to define. A collapsed lyo cake could also be a melt back. One would need to explain this difference and its criticality. 

在科学文献中，熔回被认为是严重缺陷。塌陷和熔回的区别很难定义。坍塌的冻干粉饼也可能是熔回。人们需要解释这种区别及其严重性。

SP1 Our DP is a powder. Is visual inspection of the reconstituted solution sufficient? 

SP1 我们的 DP 是一种粉末。对复溶溶液的目视检查是否足够？

100% visual inspection of the delivered DP is a general requirement. The inspection of the reconstituted solution would be part of the release process. According USP<1790> special sampling plans according S-3 and S-4 (ANSI/AQS Z1.4) should be used. 

对交付的 DP 进行 100% 的目视检查是一般要求。检查复溶溶液将是放行过程的一部分。根据 USP<1790>，应使用 S-3 和 S-4(ANSI/AQS Z1.4) 的特殊采样计划。

SP2 How should the operators performing the supplemental testing be qualified? 

SP2 进行补充测试的操作人员应如何确认资质？

Supplemented testing is performed on reconstituted vials and thus has to be performed in a lab environment. The reconstituted vials are tested either by manufacturing operators or QC staff based on the same criteria as training for 100 % visual inspection or AQL testing. 

补充测试是在复溶西林瓶上进行的，因此必须在实验室环境中进行。复溶西林瓶由制造商操作员或质量控制人员根据与 100% 目视检查或 AQL 测试用于培训的相同标准进行测试。

SP3 What is the recommendation for AQL setting for the testing of samples after reconstitution? 

SP3 复溶后样品测试的AQL 设置建议是什么？

This depends on the nature of the product. Taking 0.65 will in many cases disqualify nearly all batches. In some cases it might be an option to allow a second level testing to avoid that 1 single particle in one vial out of 20 requires rejection of your batch. 

这取决于产品的性质。在许多情况下，采用 0.65 会使几乎所有批次都不合格。在某些情况下，允许进行二级测试可能是一个选择，以避免在 20 个西林瓶中有一个西林瓶中的单个颗粒使得你的批次被剔除。

RA1 If the 100% visual inspection is followed by an AQL testing, do we have to perform also an test on visual particles at the release (testing) of the batch? 

RA1 如果 100% 视觉检查之后是 AQL 测试，我们是否还必须在批次放行 (测试) 时对视觉颗粒进行测试？

The AQL testing is intended to replace testing for visible particles at release testing in the lab. However, if this test is part of your filing, this has to be done. Or you have to file a variation. 

AQL 测试旨在取代实验室放行测试中可见颗粒物的测试。然而，如果这项测试是你提交文件的一部分，就必须进行。或者你必须提交一个变更。

RA2 Is the carrying out of a 100% inspection of parenterals to be understood as IPC testing or as final product testing? Is it possible to carry it out under the responsibility of production or must it be done by QC? 

RA2 对注射剂进行100% 检查是应该理解为 IPC 测试还是最终产品测试？是否可以在生产责任下进行，还是必须由 QC 来完成？

Assigning the activity of a 100% inspection is not trivial at first sight. Formally, this activity is allocated to production. By the way, this is also FDA's point of view. Hence, it also is an activity which requires a manufacturing authorisation within the meaning of § 13 German Medicine Act (AMG). Due to the fact that it is a 100% inspection, it is neither a real IPC nor a final inspection on a random basis. The 100% inspection being attributed to production, it is carried out under the responsibility of the head of production 

分配 100% 检查的活动乍看之下并非微不足道。形式上，这项活动被分配给生产。顺便说一下，这也是 FDA 的观点。因此，它也是一项需要在《德国医药法》第 13 条 (AMG) 意义上获得制造许可的活动。由于它是 100% 检查，因此既不是真正的 IPC，也不是随机的最终检查。100% 检查归因于生产，由生产负责人负责执行。

RA3 Are there legal acceptance criteria or provisions regarding the size of (visible) particles? 

RA3 是否存在关于 (可见) 颗粒尺寸的法律验收标准或规定？

According to studies by Jules Knapp, people can recognise particles under optimal conditions from 30 - 50 µm, taking into account the colour of the particle. Other studies have shown that eventually particles from approximately 200 µm can be surely detected - in other sources, values of 50-80 µm can be found. There are (still) no statutory limits on the size of the visible particles 

根据 Jules Knapp 的研究，在最佳条件下，人们可以识别 30-50μm 的粒子，并考虑粒子的颜色。其他研究表明，最终肯定能检测到约 200μm 的粒子——在其他来源中，可以找到 50-80μm 的值。对于可见粒子的尺寸，目前 (仍) 没有法定限值。

RA4 What does essentially free from particles mean with respect to the US and EU pharmacopeia? Is there a difference? 

RA4 对于美国和欧盟的药典来说，本质上无颗粒意味着什么？有什么区别吗？

Up to now there is no official statement from the EMA about the interpretation of “essentially free from particles”. 

迄今为止，EMA 还没有就 “本质上无颗粒” 的解释发表官方声明。

RA5 How has the limit for inherent particles to be set in a registration of a new protein product which is known to form particles? 

RA5 在已知能形成粒子的新蛋白质产品的注册中，如何设定固有粒子的限值？

The guidance according USP<1790> would be to define a limit and to monitor this limit. Of Course this limit needs then to be described within the dossier of the DP. 

根据 USP<1790>指南，将是定义一个限值并监控这个限值。当然，这个限值随后需要在 DP 的档案中进行描述。

PC1 How can Process Control Limits in the Visual inspection process be defined?/ 如何定义视觉检查过程中的过程控制限值？

Typical limits for product and production line need to be established. Therefore see chapter 6 of the Best-Practice Paper. This follows the ASTM E2587-2 standard (Standard Practice for Use of Control Charts in Statistical Process Control).

需要建立产品和生产线的典型限值。因此，请参阅最佳实践论文的第 6 章。本文遵循 ASTM E2587-2 标准 (统计过程控制中使用控制图的标准实践)。

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