20141126 ECA新闻：关于目视检查的新问答

北重楼

New Q&A concerning Visual Inspection

关于目视检查的新问答

The topic 100 percent visual control of parenterals constantly raises new questions, especially as concerns the use of automatic inspection machines or if statistical issues emerge concerning AQL inspections. Following you will find some of these questions and answers by Dr. Tobias Posset (Head of Production Support at Roche Diagnostics).

关于注射液100%目视控制不断冒出了新的问题，特别是关于使用自动检测设备，以及是否统计学问题与AQL检查合关的问题。以下是DR.TOBIAS POSSET（罗氏诊断生产支持部门领导）对这些问题的回答。

Question: What are the differences between qualification, particle (Knapp test) and function test set?
Answer: 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 ?m, vials with missing stoppers....

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.

Particle test set (Knapp-Test): Sets that contain only particles. These are particles having the size from 50?m to 1000?m 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.

问：确认、颗粒（KNAPP 灯检）和功能测试系列样品之间有什么区别？

答：功能性测试系列样品用于一种系统适用性测试，即，使用该测试来测试每批生产前和生产后监控工作正常。通常，不需要使用挑战性样品，但应含有能100%被检出的颗粒物，例如粒径为100?m的颗粒、塞子丢失的瓶……

确认测试系列：确认测试系列包括装有产品的特定容器的产品，有所有已知的统计学缺陷（刮痕、掀开错误、塞子丢失……）。通常，一组容器中约有10-20%有一个缺陷。新的不合格或缺陷要增加到确认测试系列中。

颗粒测试系列（KNAPP-TEST）：只含有颗粒的样品系列。这些颗粒的直径从50?m到1000?m，由不同成分组成（塑料、塞子材料、玻璃的材料、金属）。因此，这些样品是非静态的，即，该缺陷是在容器内或在药品溶液内。颗粒测试系列样品是确认测试系列的一部分，应同时测试。

Question: Should all these test sets be prepared artificially? Should this be done, for instance, by an external laboratory with defined failures?
Answer: We prepare the static defects in-house and a part of the non-static 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.

问：这些测试系列样品必须人工制备吗？是否可以，例如，由一个外部化验室根据指定的不合格情况制备呢？

答：我们在公司内制备常发生的缺陷样品，有一些不常发生的缺陷样品则由外部制备。但也可能将所有样品交由外部制备，而统计学缺陷种类应与你的生产设备在最差情况下产生的缺陷一致。因此，我建议你在公司内制备这些样品，并获得QA的放行。这样，你就会有你工艺中具有代表性的不好的样品。理想的情况下，你可以从你生产工艺中取出不好的样品，但没法获得所有的样品。

Question: 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? I.e. is it necessary to repeat the man-machine-comparison that was carried out in PQ?
Answer: 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.

问：再确认：如果常规自动化检查设备的再验证需要测试5000个样品，是不是表示一个批号中的这5000瓶必须同时采用人工控制和自动检查设备进行检查？也就是说，在PQ中是否需要重复人与设备的比较？

答：基本正确。PQ包括颗粒检查（KNAPP检查），检查关注“状态”缺陷，以及5000支好瓶。该5000个生产批每年每产品做一次就可以。KNAPP检查和“状态”检查不需要重复，除非颗粒检测站有变更。没有变更的情况下（很少发生）只需要测试5000瓶就可以，也就是自动检查设备检查的5000瓶由人工和机器同时检查。
Question: Is it also required to carry out the AQL test with 1,250 randomised vials for the requalification?
Answer: We carry out an evaluation of the AQL values instead of the test of 5,000. In the course of the AQL test the man-machine-comparison is already carried out so that the test of 5,000 can be skipped. Once a year a report is written for each product and the automatic inspection machine is considered to be requalified from AQL test to AQL test (= continuous requalification). This means that we are carrying out a man-machine-comparison for far more than 5,000 vials for our production of market products in one year. This means that we are getting a better statistic (depending on the product in some cases up to 30,000 vials). The automatic inspection machine has already decided "GOOD" and now this is verified by a person in the course of the AQL.

问：再验证时，是否也需要采用1250个随机瓶进行AQL测试？

答：我们采用AQL值评估来替代检测5000瓶。在AQL测试中，已经实施了人工—机器比较，所以可以省略5000瓶的检测。每年每个产品编写一份报告，就可以认为自动检测设备已经进行了AQL再确认（=持续再确认）。这表示我们在一年里对上市产品的生产实施人工—机器比较的瓶数远远超过了5000瓶。这表示我们有了一个更好的统计学数据（取决于产品，有时需要增加至30000瓶）。自动检测设备已经被认为是“好的”，现在由一个操作人员在AQL过程中来确认而已。

Question: 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.
Answer: 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 Best Practice Paper on Visual Inspection. A control of the rejection rate is also expected but it rather serves for recognizing if a batch differs from the normal unobtrusive production.

问：我们生产许多不同规格的产品。直到现在，我们仍使用不合格率<2%作为可接受标准，采用生产过程取样来控制机器的功能。

答：每批均需实施AQL测试。同时，这也是药监部门和检查员希望看到的。这在ECA的目视检查最佳规范概念中也有描述。同时也期望对不合格率进行控制，

Question: The problem is that sets of samples have to be remade regularly since they have expired. How do you prepare the function test set?
Answer: 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.

问：问题是样品系列必须定期重新制备，因为它们会过期。你如何制备功能测试系列样品？

答：通常，我们的测试样品会保持几年。必须不断替代单个样品。这些单个样品再由QA放行，我们将他们引入该系列样品中。样品系列必须至少每年1次进行控制，然后再次放行。

Question: Can we have some representative test sets prepared by an external laboratory and use them in the long term?
Answer: On principal, test sets can also be prepared by external laboratories. But there should be an internal procedure to test the sets for their suitability and to release them. At least once a year it should be controlled if the set is still representative and then it should be released again. In the ECA Best Practice Paper we even recommend to carry out this practice twice a year.

问：我们是否可以让外部化验室准备一系列的代表性测试样品，并长期使用它们？

答：原则上来说，测试系列样品也可以由外部化验室制备。但是，应该有一个内部程序来对测试这些样品的稳定性，并放行。如果该系列仍具有代表性，那至少每年一次进行控制并再次放行。在ECA最优规范概念中，我们甚至推荐1年做2次这样的测试和放行。

Question: 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)?
Answer: If I were in your place I would also carry out a bracketing. The rationale using viscosity is completely ok.

问：我们有近50个不同的液体溶液，共近百个品种（一种溶液做成几种包装）。到目前为止，我们已根据生产拒收情况制备了一套样品（功能系列、确认系列包括KNAPP系列）。这实际上很费时间。你觉得是否可以对50种溶液的一些参数，例如粘度、表面张力进行测量，然后将其分组（括号法）？

答：如果我是你，我也会采用分组法。采用粘度的合理性是完全OK的。

Question: Can an automatic inspection machine also inspect oily solutions?
Answer: There is no reason why an inspection of oily substances shouldn't be carried out. But in this case an internal qualification should be carried out since the viscosity changes the physical reaction of the particles.

问：自动检测设备也能用于检测油性溶液吗？

答：没理由不能采用自动检测设备检测油性物质。但是在这种情况下，需要进行内部确认，因为粘度会改变颗粒的物理特性。

Question: 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?
Answer: 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 be released. This guarantees that the failures are typical and that you can use them for training.

问：对员工的资质确认（培训）所用的一系列样品是要直接从生产拒收的产品中采样，还是应该根据典型的缺陷人为制造？

答：通常，培训系列样品应直接从生产拒收产品中取出。但不幸的是，一些不合格情况的发生率很低，因此，你不得不人为制造一些。最后，你会有一套典型的不合格样品，这样，就能保证不合格样品是具有代表性的，你可以使用这些样品来进行培训。

一沙一叶

学习一下。   

野性之吻

谢谢分享

道路漫长黑暗

这个很实用，学习一下

lumang

还是没看明白，如何进行AQL测试

实崇融

谢谢老师的分享。