近日，ECA发布最新版的ECA《无菌产品灯检指南-2025》，以为制药行业中对无菌产品进行100%目视检查的过程提供最佳实践建议，核心是规范人工、半自动及全自动检查的流程、要求与标准。

文件规定目视检查位置的照度应至少为2000勒克斯。对于吹灌封产品，建议照度为10000勒克斯。使用CRI指数，色彩还原度应最好具有大于90%的RA值。检查照度的适当间隔至少为每6个月一次。测试点应非常靠近操作人员的检查位置。环境照度不得干扰工作场所的照度，并且在可能的情况下，应在检查期间调低。应避免反光表面。

文件指出，环境条件对该操作的质量有很大影响。环境温度通常应为室温，夏季不应超过23°C，除非另有正当理由。相对湿度和空气流速应加以控制，以确保舒适的工作条件。噪音水平应低于55分贝。

目视检查人员的确认应针对每种剂型（例如注射器、小瓶、安瓿）分别进行。确认过程中待检查的单元数量应与日常工艺中一次休息到下一次休息期间所检查的物品数量一致。在初始确认中，应识别出所有关键缺陷以及预先确定的主要缺陷等级。此外，还应预先确定误判拒收（无缺陷样品被拒收）的限度（例如，5-10%）。日常再确认应至少每12个月进行一次。

对于人工灯检，要求每个物品应在白色背景下检查约5秒，在黑色背景下再额外检查5秒。应规定两次休息之间连续检查活动的最长时间，以及一个班次/工作日的总最长检查时间。行业惯例是检查20-60分钟。当前的良好实践目标是检查30分钟后至少休息5分钟，总持续时间目标不超过4小时。所有最长不间断检查活动都应经过确认。

对于半自动检查，检查间应隔绝外部光源，应确保单元在检查区域内至少完整旋转360°，并对单元的顶部和底部进行检查，检查区域的照度度通常高于人工检查（例如8000勒克斯），操作员的坐姿应符合人体工学，使操作员的视觉焦点对准检查位置。还应定期确认设备的潜在漂移（例如照度），例如至少每六个月一次。

对于全自动检查，PQ应针对具体产品开展，确认套件应至少检查十次，以确保统计稳健性。应考虑所谓的克纳普测试（Knapp Test）原理。确认套件通常包含约10%的缺陷单元以防止偏差。全自动检查系统的再确认理想情况下应每年进行一次，最迟每两年进行一次。

关于灯检缺陷分析的行动限要求必须根据生产历史按具体产品确定。若没有以往经验，单个缺陷的典型行动限值例如：

关键缺陷：0.5%至1% *

主要缺陷：3%至5%

微小缺陷：5%至10%

对于关键缺陷，严重性限值（如影响无菌性的缺陷（例如浑浊、裂缝或混淆）等GMP问题，表明GMP符合性为0，需启动调查。

一旦确定根本原因，且检查方法适用于挑出导致问题的缺陷，可对批次进行复检。未事先调查不得进行复检。复检方法的决定应由批准且受权的人员做出。不得对拒收的容器进行复检。

对于批放行，典型的最低AQL要求为：

关键缺陷：AQL样品中无缺陷

主要缺陷：≤0.65 AQL

微小缺陷：≤4.0 AQL

2025版ECA无菌产品灯检指南发布

 

 

 

 

 

文件翻译如下：

 

 

 

Table of Contents

目录

 

1 SCOPE

1 范围

2 MANUAL INSPECTION

2 人工检查

2.1 Workplace

2.1 工作场所

2.2 Personnel

2.2 人员

2.3 Regulatory expectations

2.3 法规要求

2.4 Operation

2.4 操作

3 SEMI-AUTOMATED INSPECTION

3 半全自动检查

4 AUTOMATED INSPECTION – QUALIFICATION, VALIDATION AND ROUTINE OPERATION

4 全自动检查——确认、验证和日常操作

4.1 General

4.1 总则

4.2 IQ & OQ – Installation and Operational Qualification

4.2 安装确认与运行确认

4.3 PQ – Performance Qualification

4.3 性能确认

4.4 Validation

4.4 验证

4.5 Requalification and Revalidation

4.5 再确认和再验证

4.6 Routine operation

4.6 日常操作

5 INSPECTION OF DIFFICULT-TO-INSPECT PRODUCTS AND CONTAINERS

5 难检查产品和容器的检查

5.1 Inspection of lyophilized product

5.1 冻干产品的检查

5.2 Brown glass, coloured/turbid solutions

5.2 棕色玻璃、有色/浑浊溶液

6 DEFECT CLASSES

6 缺陷类别

7 EVALUATION OF DEFECT CLASSES AND TRENDING

7 缺陷类别评估与趋势分析

7.1 Manual, semi-automated and fully automated inspection

7.1 人工、半自动化和全全自动检查

8 BATCH CERTIFICATION/RELEASE

8 批次认证/放行

9 CONCERNS REGARDING DISTRIBUTED PRODUCT

9 已分销产品的相关问题

10 DEFINITIONS

10 定义

11 REFERENCES

11 参考文献

 

1 Scope

1 范围

 

This paper aims to highlight best practices for carrying out 100 % visual inspection of medicinal products for parenteral use in the Pharmaceutical Industry. It should be seen in addition and complementary to the monographs of the different Pharmacopoeias.

本文旨在强调制药行业对无菌药品进行100%目视检查的最佳实践。它应被视为对不同药典专著的补充。

 

Visual inspection of medicinal products for parenteral use should detect any readily identifiable visible container defect and ensure constant quality of the product in terms of absence of particulate matter and/or turbidity, and correct or uniform appearance of a lyo cake.

对无菌药品的目视检查应能发现任何易于识别的可见容器缺陷，并从无颗粒物质和/或浑浊、冻干产品外观正确或均一等方面确保产品质量的稳定性。

 

Modifications of the procedures and figures proposed in this paper are possible at any time. However, following the proposed procedures and figures may lead to safer inspection processes and may avoid discussions in GMP audits and inspections, as the described approach reflects current practice and has shown its suitability during many years of industrial operation and GMP inspections.

本文中提出的程序和图表可随时修改。然而，遵循所提出的程序和图表可能会使检查过程更安全，并可能避免在GMP审计和检查中出现争议，因为所描述的方法反映了当前的实践，并且在多年的行业操作和GMP检查中已证明其适当性。

 

The CCI (Container Closure Integrity) topic is out of scope of this paper (see ECA position paper “Container Closure Integrity testing of medicinal products for parenteral use”).

容器密封完整性（CCI）主题不在本文范围内（参见ECA立场文件《无菌药品的容器密封完整性测试》）。

 

2 Manual Inspection

2 人工检查

 

2.1 Workplace

2.1 工作场所

 

The area where manual visual inspection is performed should be suitable for this operation. Besides common GMP requirements for manufacturing or quality control areas, the following inspection conditions are of substantial importance:

进行人工目视检查的区域应适合该操作。除了生产或质量控制区域的常见GMP要求外，以下检查条件至关重要：

 

Illumination:

照度：

 

The intensity of the illumination at the inspection point should have at least 2000 lux. For Blow-Fill-Seal products, an illumination of 10.000 lux is recommended (see also chapter 5). Accuracy of the lux-meter measuring light intensity should be considered. The colour reproduction, using the CRI index, should preferably have an RA value > 90%.

检查位置的照度强度应至少为2000勒克斯。对于吹灌封产品，建议照度为10000勒克斯（另见第5章）。应考虑照度计测量光强度的准确性。使用CRI指数，色彩还原度应最好具有大于90%的RA值。

 

Illumination should be regularly qualified and part of the preventive maintenance programme. An appropriate interval for checking the illumination is at least every 6 months. It is recommended that the technical measurement used to determine the light intensity is performed at a prefixed point, which should be very close to the inspection point of the operator.

照度应定期确认，并应是预防性维护计划的一部分。检查照度的适当间隔至少为每6个月一次。建议用于确定光强度的技术测量在一个预先设定的点进行，该点应非常靠近操作人员的检查位置。

 

The ambient illumination must not interfere with the illumination of the workplace and should be turned down during inspection, if possible. Reflecting surfaces should be avoided.

环境照度不得干扰工作场所的照度，并且在可能的情况下，应在检查期间调低。应避免反光表面。

 

Ambient conditions:

环境条件：

 

Ambient conditions have a high impact on the quality of this operation. Ambient temperature should normally be at room temperature and should not exceed 23 °C in summer, unless otherwise justified. Relative humidity and air velocity should be controlled and ensure comfortable working conditions. The noise level should therefore be below 55dB (source: German Workplace Ordinance ArbStättV).

环境条件对该操作的质量有很大影响。环境温度通常应为室温，夏季不应超过23°C，除非另有正当理由。相对湿度和空气流速应加以控制，以确保舒适的工作条件。噪音水平应低于55分贝（来源：德国工作场所条例ArbStättV）。

 

2.2 Personnel

2.2 人员

 

Personnel involved in the visual inspection should regularly undergo eye tests. The optometrist should focus on the ability to discriminate small differences in uniform structures, e.g. open/closed circles. Also, colour vision of the inspector should be tested.

参与目视检查的人员应定期进行眼科检查。验光师应关注辨别均匀结构中细微差异的能力，例如开/闭的圆圈。此外，还应测试检查人员的色觉。

 

Personnel performing visual inspection should be qualified, comprising initial qualification and periodic requalification. Qualification should be specific for each dosage form (e.g. syringe, vial, ampoule).

进行目视检查的人员应进行确认，包括初始确认和定期再确认。确认应针对每种剂型（例如注射器、小瓶、安瓿）分别进行。

 

Initial qualification should follow a predefined schedule, starting with the introduction of the new employee to training kits. These training kits should contain all kinds of defects and should be updated constantly with new evolving defects out of production. These training kits should be specific for the dosage form. In case of unstable defects or defects which are not available photos of defects or artificial defects may be used.

初始确认应遵循预先设定的程序，从向新员工介绍培训套件开始。这些培训套件应包含各类缺陷，且应随着生产中出现的新缺陷不断更新。培训套件应针对具体剂型。若存在不稳定的缺陷或无法获取缺陷照片的情况，可使用人工缺陷。

 

A bracketing approach for different products is acceptable when process equivalence is scientifically justified. Following the training via training kits there should be a side-by-side training with an experienced operator. The trainee should have the chance to ask questions with the experienced operator performing a parallel 100 % inspection of the inspected units of the trainee.

当工艺等效性有科学依据时，对不同产品采用分组法是可接受的。通过培训套件完成培训后，应与有经验的操作员进行结对培训。受训人员应有机会向有经验的操作员提问，操作人员同时对受训人员检查的单元进行100%平行检查。

 

Following successful completion of the side by side training, the initial qualification should be performed using a qualification kit. This kit should focus on critical and major defects and also contain a limited number of minor defects. The number of units to be inspected should represent the number of objects which are inspected in the routine process from one eye break to the next eye break.

在成功完成结对培训后，应使用确认套件进行初始确认。该套件应关注关键和主要缺陷，同时包含一定数量的微小缺陷。待检查的单元数量应与日常工艺中一次休息到下一次休息期间所检查的物品数量一致。

 

2.3 Regulatory expectations

2.3 法规期望

 

The European GMP requirements with regard to the visual inspection are - among others - included in EU GMP Guide, Annex <1> “Manufacture of Sterile Products” in the section “Finishing of sterile products”. This guidance document addresses expectations relevant to visual inspection.

EU GMP中关于目视检查的要求，除其他外，包含在欧盟GMP指南附录1《无菌产品的生产》中“无菌产品的最终处理”部分。该指导文件阐述了与目视检查相关的期望。

 

Despite the fact that current regulations cover many topics concerning visual inspection, situations may occur where expectations of a regulatory inspector differ from to the scientific understanding of the pharmaceutical company.

尽管当前法规涵盖了许多与目视检查相关的主题，但仍可能出现监管检查人员的期望与制药公司的科学理解存在差异的情况。

 

Expectation 1:

期望1：

 

There is sometimes the expectation for operators to wear corrective lenses when undergoing visual inspection qualification, if they are worn during daily life.

往往会期望操作员在进行目视检查确认时，若日常生活中佩戴矫正镜片，则需佩戴该镜片。

 

Corrective lenses are used to shift an observed object into the focus point of the human eye. It is a known fact that individuals may shift an observed object into their (individual) eye focus point simply by varying the distance to the object, without the use of corrective lenses. Operators need correct corrective lenses in everyday life might be able to perform visual inspection without.

矫正镜片用于将观察到的物体移至人眼的焦点。众所周知，不使用矫正镜片时，个体仅通过改变与物体的距离，就可将观察到的物体移至其眼睛焦点。日常生活中需要佩戴矫正镜片的操作员可能在不佩戴的情况下进行目视检查。

 

The requested medical check should examine e.g. three-dimensional sight, color identification, stigmatic corrections and most importantly reflecting the normal “daily life” visual capability. This ensures that the operator can see defects.

要求的医疗检查应检查例如立体视觉、颜色识别、散光矫正，最重要的是反映正常“日常生活”中的视觉能力。这确保操作员能够发现缺陷。

 

The medical check is not related to the competence of performing visual inspection activity. This is checked during qualification of the operator and whether he has to wear visibility aids is determined during this process.

医疗检查与执行目视检查活动的能力无关。这在操作员确认期间进行检查，且其是否需要佩戴视觉辅助设备也在该过程中确定。

 

Expectation 2:

期望2：

 

There is sometimes the expectation for operators to be qualified considering different stress factors, including fatigue at the end of shift. It can be doubted that a fatigue effect can be simulated in an examination situation which has an impact on the operator whether he/she can keep his/her job. With this there is always nervousness, and some people have even examination anxiety which leads to release of Adrenaline in the human body which counters a fatigue effect. Additionally, when performing initial qualification, the fatigue at the end of shift can’t be simulated anyway, as the operators are not yet allowed to perform a “normal” visual inspection workday.

有时会期望在对操作员进行确认时考虑不同的压力因素，包括换班结束时的疲劳。在会影响操作员是否能保住工作的考试情境中，能否模拟疲劳效应是值得怀疑的。这种情况下总会存在紧张情绪，有些人甚至有考试焦虑，这会导致人体释放肾上腺素，从而抵消疲劳效应。此外，在进行初始确认时，换班结束时的疲劳无论如何都无法模拟，因为操作员尚未被允许进行“正常”的目视检查工作日。

 

As Annex 1 requests that “operators performing visual inspection should be following a work and rest regime specifically designed to minimize distractions, there should be no fatigue effects at end of shift, which would impact the validity of the visual inspection.

正如附录1要求“进行目视检查的操作员应遵循专门设计的工作和休息制度，以尽量减少干扰，换班结束时不应出现疲劳效应，否则会影响目视检查的有效性。

 

Keeping this in mind, it should be considered to address these two topics/aspects/expectations by a Quality Risk Management approach.

考虑到这一点，应考虑通过质量风险管理方法来处理这两个主题/方面/期望。

 

Acceptance criteria for the qualification should be predefined. In the initial qualification all critical defects and a predefined level for major defects should be found. Also, a limit for the False Rejects (rejection of samples without defects) should be predefined (e.g., 5-10%).

应预先确定确认的接受标准。在初始确认中，应识别出所有关键缺陷以及预先确定的主要缺陷等级。此外，还应预先确定误判拒收（无缺陷样品被拒收）的限度（例如，5-10%）。

 

Routine requalification should be performed at least every 12 months. After a second significant inspection failure the operator should undergo a repeated eye test and a subsequent new qualification with the training kit as well as a subsequent new qualification via a qualification kit.

日常再确认应至少每12个月进行一次。在第二次重大检查失败后，操作员应重新进行视力测试，随后使用培训工具包进行新的确认，并通过确认工具包进行后续的新确认。

 

2.4 Operation

2.4 操作

 

Routinely, during the 100 % inspection each object should be inspected for at about 5 seconds against a white background and an additional 5 seconds against a black background. Times may be shorter when using a semi-automatic system. The objects should be slightly twisted or slowly rotated to swirl up particles whilst avoiding the formation of air bubbles.

通常，在100%检查过程中，每个物品应在白色背景下检查约5秒，在黑色背景下再额外检查5秒。使用半自动系统时，检查时间可能更短。物品应轻微扭转或缓慢旋转，使颗粒旋起，同时避免气泡形成。

 

The post inspection recovery time for visual Inspection staff is of essential importance. The maximum time for continuous inspection activity between breaks and the total maximum inspection time for a shift/workday should be defined.

目视检查人员的检查后恢复时间至关重要。应规定两次休息之间连续检查活动的最长时间，以及一个班次/工作日的总最长检查时间。

 

Industry practice is 20-60 minutes of inspection. A current good practice goal is 30 minutes of inspection followed by a break of at least 5 minutes continued for a total maximum duration goal of no longer than 4 hours. All maximum uninterrupted inspection activity should be qualified.

行业惯例是检查20-60分钟。当前的良好实践目标是检查30分钟后至少休息5分钟，总持续时间目标不超过4小时。所有最长不间断检查活动都应经过确认。

 

3 Semi-Automated Inspection

3 半自动检查

 

Semi-automated visual inspection is the combination of manual visual inspection and an automated transporting system of the units. The inspection system presents the object to a human inspector allowing inspection of the units using a defined set-up (inspection booth) and a qualified human operator.

半自动目视检查是人工目视检查与单元自动传输系统的结合。检查系统将物品呈现给人工检查人员，允许检查人员使用规定的装置（检查间）和经确认的人工操作员对单元进行检查。

 

The complete inspection of each unit is ensured by the following aspects:

每个单元的完整检查通过以下方面确保：

 

To avoid disturbances of the inspector, an inspection booth should exclude external light sources.

为避免干扰检查人员，检查间应隔绝外部光源。

At least a full 360° rotation of the unit in the inspection field facilitates inspection.

单元在检查区域内至少完整旋转360°，便于检查。

Inspection of the top and the bottom of the unit ensures complete inspection of the unit.

对单元的顶部和底部进行检查，确保单元的完整检查。

For liquid products, particle inspection can be supported by pre-rotating the objects before inspection to get the particles moving within the solution.

对于液体产品，可在检查前预先旋转物品，使颗粒在溶液中移动，以辅助颗粒检查。

Due to the nature of semi-automated inspection the inspection field is typically illuminated higher than in manual inspection (for example 8,000 lux) and may be adjusted to suit for difficult to inspect objects. Inspection of difficult to inspect objects are described in chapter 5.

由于半自动检查的特性，检查区域的照度度通常高于人工检查（例如8000勒克斯），并且可根据难以检查的物品进行调整。难以检查物品的检查在第5章中描述。

For an undisturbed visual inspection, the surrounding of the booth should be designed in such a way to prevent extraneous light and/or reflections.

为了实现无干扰的目视检查，检查间的周边应设计成可防止外来光线和/或反射的形式。

Magnification or other suitable aids should be used in order to bring the visual focus point of the operator’s eyes to the point of inspection using an ergonomic sitting situation of the operator.

应使用放大设备或其他合适的辅助工具，结合操作员符合人体工学的坐姿，使操作员的视觉焦点对准检查位置。

 

Risk Management Principles as part assessments should be established and then implemented in a controlled manner noted above. Pre-start up tests should be used during qualification of all the variable parameters to be used periodically. Functional control kits should be used to ensure variable parameters are within the validated state before commencement of the inspection process, whereas potential drifts of the equipment (e.g., Illumination) is more suited to be verified periodically, e.g., at least every six months.

风险管理原则作为部分评估应予以建立，然后以上述受控方式实施。在对所有定期使用的可变参数进行确认时，应使用启动前测试。功能控制工具包应用于确保在检查过程开始前可变参数处于验证状态，而设备的潜在漂移（例如照度）更适合定期确认，例如至少每六个月一次。

 

The most important parameters are:

最重要的参数有：

 

Conveyor Speed

传送带速度

Illumination

照度

pre-spinning / if applicable

预旋转/若适用

Rotation within the inspection field to ensure 360-degree inspection of the unit

检查区域内的旋转，以确保对单元进行360度检查

 

Validation of the semi-automated inspection process should show at least equivalence to manual inspection results.

半自动检查过程的验证应至少显示出与人工检查结果相当的水平。

 

For lyophilized products, inspectors are qualified at maximum inspection speed and may inspect during routine operation at maximum or any lower inspection speed.

对于冻干产品，检查人员需在最高检查速度下确认，且可在日常操作中以最高速度或任何更低速度进行检查。

 

For liquid products, inspection at the qualified speed should be routinely used at all times due to the influence of speed on the inspection validity.

对于液体产品，由于速度会影响检查有效性，应始终常规使用经确认的速度进行检查。

 

After an inspection process of an uninterrupted and predefined duration, operators require an eye break. Semi-automated visual inspection requires greater concentration by the operator. For that, times of uninterrupted inspection are typically shorter than manual visual inspection and times of breaks may differ from the numbers given in chapter 2.3 (Operation of the Manual Visual Inspection).

在一段不间断且预定义时长的检查过程后，操作人员需要让眼睛休息。半自动目视检查要求操作人员更加集中注意力。因此，不间断检查的时长通常比人工目视检查更短，休息时长也可能与第2.3章（人工目视检查的操作）中给出的数值不同。

 

4 Automated Inspection – Qualification, Validation and Routine Operation

4 全自动检查——确认、验证和日常操作

 

4.1 General

4.1 总则

 

The central aspect of qualification and validation of a fully automated inspection machine is the verification that the machine is at least as good as the comparative group of human inspectors (without magnification) with regards to defect detection rates. Qualification and validation can be done consecutively or combined.

全自动灯检机确认和验证的核心方面是，在缺陷检出率方面，验证该设备至少与人工检查人员组（不使用放大设备）水平相当。确认和验证可连续进行或结合进行。

 

Basically, qualification is the documented evidence that the inspection machine is fit for purpose, while validation is the documented evidence that the machine achieves reproducible results of desired quality in the manufacturing process. In simple terms, the qualification is done to ensure that the machine works as specified (URS), whereas the validation ensures that it consistently delivers the desired (inspection-) results in the manufacturing process.

从根本上说，确认是证明灯检机适用用途的书面证据，而验证是证明该设备在生产过程中能稳定产出符合预期质量的可重复结果的书面证据。简而言之，确认是为了确保设备按规定（URS）运行，而验证是为了确保其在生产过程中持续交付预期的（检查）结果。

 

4.2 IQ & OQ – Installation and Operational Qualification

4.2 安装确认（IQ）与运行确认（OQ）

 

Qualification begins with the development of the user requirements and ends with the verification of proper implementation. As part of the qualification phases, it should be confirmed that the machine complies with the user requirements specifications (URS).

确认始于用户需求的制定，终于对正确实施的验证。作为确认阶段的一部分，应确认设备符合用户需求说明（URS）。

 

Installation Qualification (IQ) usually includes verification of the correct installation of components and equipment against technical drawings and specifications and the provision of the agreed operating and work instructions and maintenance requirements by the supplier.

安装确认（IQ）通常包括根据技术图纸和规范验证部件和设备的正确安装，以及供应商提供约定的操作和工作指令及维护要求。

 

Operational Qualification (OQ) covers cross-product and format-specific functionality tests such as

运行确认（OQ）涵盖跨产品和特定规格的功能测试，例如

 

the management of users, recipes, alarms, and warnings

用户、配方、警报和报警的管理

proper transport, handling, and ejection of units for all formats

所有规格下单元的正确输送、处理和排出

counting of units, batch report and audit trail functionality

单元计数、批次报告和审计追踪功能

presentation of the units in front of the cameras, such as correct positioning, rotation, illumination, etc.

单元在摄像头前的呈现，例如正确的定位、旋转、照度等

 

4.3 PQ – Performance Qualification

4.3 性能确认（PQ）

 

As part of the PQ, documented evidence should be provided demonstrating that the automated inspection machine (AIM) fulfills the defined performance requirements under intended (real) production conditions.

作为PQ的一部分，应提供书面证据，证明自动化灯检机（AIM）在预期（实际）生产条件下满足既定的性能要求。

 

The central aspect of performance qualification is the verification that the AIM performs at least as well as the comparative group of qualified human inspectors (without magnification) regarding defect detection capability. PQ should be performed product specific.

性能确认的核心方面是，在缺陷检查能力方面，验证AIM至少与经确认的人工检查人员组（不使用放大设备）表现相当。PQ应针对具体产品开展。

 

Throughout performance qualification, product-specific qualification kits should be used to evaluate detection rates after an appropriate number of inspections. These kits should consist of production materials, qualified substitutes, or simulated products that have been demonstrated to exhibit equivalent physical and optical characteristics relevant to automated visual inspection (e.g., size, shape, and color of defects, particle mobility), irrespective of their pharmaceutical relevance. The qualification kit should be inspected at least ten times to ensure statistical robustness.

在整个性能确认过程中，应使用针对具体产品的确认套件，在完成适当次数的检查后评估检出率。这些套件应包含生产物料、经确认的替代品或模拟产品，这些产品已被证明具有与自动化目视检查相关的等效物理和光学特性（例如，缺陷的大小、形状和颜色，颗粒流动性），无论其药学相关性如何。确认套件应至少检查十次，以确保统计稳健性。

 

Detection rates should be compared with the results of a representative group of qualified human inspectors and should be at least equivalent to manual inspection, assessed at the level of defined defect categories (comparison of individual container results is not required).

检出率应与一组有代表性的经确认人工检查人员的结果进行比较，且至少应与人工检查相当，在既定缺陷类别的层面进行评估（无需对单个容器的结果进行比较）。

 

When evaluating particle detection performance, the principles of the so-called Knapp Test should be considered. Jülius Knapp demonstrated that a ratio of not more than 25% defective units within a set of confirmed good units provides optimal statistical accuracy for determining detection performance while avoiding rejection bias. Such enrichment qualification kits typically contain around 10% defective units to prevent bias. In practice, however, qualification kits are required whenever the Knapp Test is applied in the context of a man-machine comparison to demonstrate the performance of the automated inspection system, which is typically the case for the confirmation of particle detection capability. If, however, the machine's performance is evaluated against predefined acceptance criteria, i.e., detection rates, the inclusion of good units may be omitted, as automated systems are not subject to operator bias and fatigue.

在评估颗粒检查性能时，应考虑所谓的克纳普测试（Knapp Test）原理。尤利乌斯·克纳普（Jülius Knapp）证明，在一组已确认的合格单元中，缺陷单元比例不超过25%时，在确定检查性能并避免拒收偏差的情况下，可提供最佳统计准确性。此类富集确认套件通常包含约10%的缺陷单元以防止偏差。然而，在人机对比的背景下应用克纳普测试以证明全自动检查系统的性能时，通常需要确认套件，这在颗粒检查能力的确认中尤为常见。但如果是根据预定义的接受标准（即检出率）评估设备性能，则可省略合格单元的纳入，因为自动化系统不受操作人员偏差和疲劳的影响。

 

Success is demonstrated when the machine's detection performance, based on a predefined number of at least ten repeated inspections, is statistically equivalent to that obtained from the same number of repeated manual inspections. If a higher number of repeated inspections are required, the corresponding number shall be adjusted accordingly for both the automated and manual inspections to ensure statistical comparability. This constitutes the so-called Knapp Test.

当设备基于预定义的至少十次重复检查次数，其检查性能在统计上与相同次数的人工重复检查结果相当，则证明成功。如果需要更多次数的重复检查，应为自动化和人工检查相应调整次数，以确保统计可比性。这就构成了所谓的克纳普测试。

 

Bracketing approaches may be applicable, provided that they are justified by quality approved rationales.

括号法可能可以使用，但应经质量部门批准。

 

4.4 Validation

4.4 验证

 

Validation provides documented evidence that the automated inspection machine consistently produces results of the required quality during routine manufacturing. Tests should cover the operating range, simulating the intended process supported by quality-approved protocols.

验证提供书面证据，证明自动化灯检机在日常生产中持续产出符合要求质量的结果。测试应涵盖操作范围，模拟经质量批准方案支持的预期工艺。

 

This includes confirmation of process capabilities in terms of product stability, defined AQL limits, and trend limits. Furthermore, validation is intended to provide guidance on the information and data to be provided in the regulatory submission.

这包括在产品稳定性、既定可接受质量水平（AQL）限值和趋势限值方面对工艺能力的确认。此外，验证可以为监管申报中应提供的信息和数据提供指导。

 

Validation may be performed by comparing the results of manual human inspection with those obtained from the automated inspection machine. For example, this can involve manual re-inspection of a previously inspected batch or sub-batch (e.g., 5000 units) to confirm that the machine's performance is at least as good as the comparable group of human inspectors. Alternatively, validation can be confirmed by assessing the achievement of the expected AQL limits based on a defined number of batches (e.g., three consecutive production batches).

验证可通过将人工检查结果与自动化灯检机的结果进行比较来实施。例如，这可以包括对先前检查过的批次或子批次（例如，5000个单元）进行人工复检，以确认设备的性能至少与可比较的人工检查人员组相当。或者，可通过基于规定数量的批次（例如，连续三个生产批次）评估预期AQL限值的达成情况来确认验证。

 

4.5 Requalification and Revalidation

4.5 再确认与再验证

 

Requalification of an automated inspection system should ideally be carried out annually, or every two years at the latest. Requalification should include a review of all changes and deviations that occurred during the period of operation. This review should include statistical trend analysis of performance data obtained during routine batch production. System suitability testing based on representative defect kits before and after every inspection and if necessary, additional inspections of test kits assessed may be carried out during production to ensure the inspection equipment remains in a state of control.

全自动检查系统的再确认理想情况下应每年进行一次，最迟每两年进行一次。再确认应包括对运行期间发生的所有变更和偏差的审查。该审查应包括对日常批次生产期间获得的性能数据的统计趋势分析。在每次检查前后基于代表性缺陷套件进行系统适用性测试，必要时，在生产期间对评估的测试套件进行额外检查，以确保检查设备保持在受控状态。

 

Revalidation can be performed by repeating the verification of the human inspection versus the inspection results of the machine, for example by manual re-inspection of an automatically inspected batch or part of the batch (e.g., 5000 units). The acceptance criteria are the same as during the initial validation.

再验证可通过重复验证人工检查与设备检查结果的比对来实施，例如对自动检查的批次或部分批次（例如，5000个单元）进行人工复检。接受标准与初始验证时相同。

 

In addition to such periodic revalidation activities, continuous revalidation of the automated inspection machine performance may be established through the ongoing statistical evaluation of AQL results. Since the AQL represents a manual inspection of a representative sample from every batch, this data provides continuous evidence of the machine’s inspection performance. Statistical trending of AQL results in accordance with Quality Risk Management (QRM) principles enables early detection of performance shifts. Consistent performance within predefined limits demonstrates maintained process control and can be considered a continuous confirmation of the AIM’s validated state – thus fulfilling the intent of revalidation on a batch-by-batch basis.

除了此类周期性再验证活动外，还可通过对可接受质量水平（AQL）结果的持续统计评估来建立对自动化灯检机性能的持续再验证。由于AQL代表对每批中代表性样品的人工检查，该数据可持续证明设备的检查性能。根据质量风险管理（QRM）原则对AQL结果进行统计趋势分析，可早期发现性能偏移。在预定义限值内的稳定性能表明过程控制得以维持，可被视为对自动化灯检机（AIM）验证状态的持续确认——从而实现逐批次再验证的目的。

 

Results and evaluations should be documented in a revalidation report.

结果和评估应记录在再验证报告中。

 

4.6 Routine operation

4.6 日常操作

 

During routine operation the overall functional performance of the automated system should be demonstrated to be within the acceptable range of the normal operating conditions and validated state. This is achieved by using the functional test kit containing representatives of the range of defects that has been used in the qualification, which should be applied before and after the inspection of a batch. An abridged or reduced functional test kit may also be used. In the event of a risk, such as a malfunction or machine drifts (misalignments of visual components, camera defects, etc.) of the inspection system or in the case of a prolonged inspection time (e.g., campaign production, large volume batches), the described functional test can also be useful within a batch.

在日常操作期间，应证明自动化系统的整体功能性能处于正常操作条件和验证状态的可接受范围内。这可通过使用包含确认过程中所用缺陷范围代表的功能测试套件来实现，该套件应在批次检查前后使用。也可使用简化或缩减的功能测试套件。在出现风险的情况下，例如检查系统发生故障或设备偏移（视觉组件错位、摄像头缺陷等），或在检查时间延长的情况下（例如，连续生产、大批量批次），上述功能测试在批次内也可能有用。

 

5 Inspection of difficult-to-inspect Products and Containers

5 难检查产品和容器的检查

 

All drug products must be 100% visually inspected, even if they are difficult to inspect due to their product characteristics and/or container. A difficult to inspect product may be defined as either cloudy (suspension products) or turbidly oily products (emulsions) or a mixture of these characteristics. Difficult-to-inspect containers can be defined as amber, coloured, opaque, or plastics, essentially any material that is not 100% transparent. Additionally, a small product volume sometimes may be considered as difficult to inspect.

所有药品都必须进行100%的目视检查，即使由于其产品特性和/或容器原因而难以检查。难检查产品可定义为浑浊的（混悬剂产品）、浑浊油性的产品（乳剂）或这些特性的混合物。难检查容器可定义为琥珀色、有色、不透明或塑料材质的，本质上是任何不是100%透明的材料。此外，小容量产品有时也可能被视为难以检查。

 

If any characteristics of the product cannot be visually inspected by the 100% inspection, suitable inspection methods should be used additionally, e.g., destructive random sampling. Samples are taken according to a sampling plan, please refer to DIN ISO 2859-1 or ANSI/ASQ Z1.4. In case additional testing is carried out to test for particles, the destructive testing should be performed in a grade A (ISO 100) environment at laminar conditions to avoid sample contamination with particles from the environment. During testing process, product solution is withdrawn from the container and filtered through a filter membrane (e.g., 0.8 μm pore size similar to USP <788>), prewetted with particle free water. After residues of the product are washed away with particle free water, the dried membranes are visually inspected with a stereomicroscope for particles > 100 μm (see USP <790>, AQL 0.65).

如果产品的任何特性无法通过100%目视检查进行检查，应额外使用合适的检查方法，例如破坏性随机抽样。样品根据抽样计划抽取，详情请参考DIN ISO 2859-1或ANSI/ASQ Z1.4。如果进行额外的颗粒测试，破坏性测试应在A级（ISO 100）层流环境中进行，以避免样品被环境中的颗粒污染。在测试过程中，从容器中取出产品溶液并通过过滤膜（例如，孔径0.8 μm，类似于USP <788>）过滤，该过滤膜需用无颗粒水预润湿。用无颗粒水冲洗掉产品残留物后，将干燥的滤膜用立体显微镜目视检查>100 μm的颗粒（参见USP <790>，AQL 0.65）。

 

5.1 Inspection of lyophilized product

5.1 冻干产品的检查

 

In case of lyophilized products, particles can only be detected on the cake, not within the cake during 100% visual inspection. For within-cake-inspection, a number of samples are reconstituted and visually inspected for particulates. The result must be within the predefined particle limits.

对于冻干产品，在100%目视检查期间，颗粒仅能在饼状物表面被检查到，无法在饼状物内部被检查到。如需检查饼状物内部，需将一定数量的样品复溶后，对颗粒进行目视检查。结果必须在预定义的颗粒限值范围内。

 

5.2 Brown glass, coloured/turbid solutions

5.2 棕色玻璃、有色/浑浊溶液

 

Visual inspection of products in brown glass containers or with coloured solutions are difficult to inspect in terms of particle detection for example. Detectability of other defects like fill level, closure defects or glass defects is usually not affected with such products.

例如，对棕色玻璃容器中的产品或含有色溶液的产品进行目视检查时，颗粒检查较为困难。而其他缺陷（如装量、密封缺陷或玻璃缺陷）的可检查性通常不受此类产品的影响。

 

As with brown glass containers or coloured solutions, the contrast between particles and the product is decreased. Therefore, the probability of detecting particles, in particular, small particles (> detection of particles <100 μm) or small particles is more difficult or compliance to USP 790 (detection of particles >100 μm) may be hard to achieve.

与棕色玻璃容器或有色溶液的情况类似，颗粒与产品之间的对比度降低。因此，检查颗粒（尤其是小颗粒（<100 μm的颗粒检查）或小颗粒）的难度增加，或难以符合USP 790（>100 μm颗粒的检查）的要求。

 

Decreased visibility of particles in brown glass containers or slightly coloured or slightly turbid solutions may be improved by increasing illumination, as described in ch. Eur. 2.2.20 or JP 6.06, or by extending inspection time. Also, other measures like using a pyrolyt light or different illumination wavelength may be helpful as well. Visibility due to strong colouration of liquid, milky products or in lyophilized products may be improved by video.

对于棕色玻璃容器中或轻微有色、轻微浑浊溶液中的颗粒可见性降低的情况，可通过增加照度（如欧洲药典第2.2.20章或日本药典第6.06章所述）或延长检查时间来改善。此外，使用热解光或不同的照度波长等其他措施也可能有帮助。对于因液体、乳状产品或冻干产品的强着色导致的可见性问题，可通过视频方式改善。

 

If particles are not visible to ensure correlation of product light, different products in lyophilized products, destructive testing must be used as mentioned in case of lyophilized products.

如果颗粒不可见，为确保产品光的相关性，对于冻干产品中的不同产品，必须使用如冻干产品检查中所述的破坏性测试。

 

If the product is also non-transparent (opaque) or very cloudy, microscopic examination, e.g. as described in JP 6.06. Method 2, has to be applied.

如果产品也是不透明的或非常浑浊的，必须采用显微检查，例如日本药典第6.06章方法2中所述的方法。

 

6 Defect Classes

6 缺陷类别

 

There should be at least two product-specific defect classes defined. Additional defect classes may be defined, for example:

应至少定义两个针对具体产品的缺陷类别。还可定义其他缺陷类别，例如：

 

Critical defects: may cause a lack of sterility, container integrity or cause harm to patients.

关键缺陷：可能导致无菌性缺失、容器完整性破坏或对患者造成伤害。

 

Major defects: may alter the content or the function of the product.

主要缺陷：可能改变产品的成分或功能。

 

Minor defects: Defects that do not affect patient health or a product’s functionality.

微小缺陷：不影响患者健康或产品功能的缺陷。

 

Other: If a company performs additional visual inspection for a specific cosmetic appearance for products intended to be placed to culturally sensitive markets, it is recommended not to include them into the GMP – and within-product quality related - defect classification.

其他：如果某公司针对拟投放文化敏感市场的产品，因特定外观要求而进行额外的目视检查，建议不要将这些缺陷纳入与GMP及产品内在质量相关的缺陷分类中。

 

7 Evaluation of Defect Classes and Trending

7 缺陷类别评估与趋势分析

 

7.1 Manual, semi-automated and fully automated inspection

7.1 人工、半自动和全自动检查

 

Based on the trend analysis of the production process, a limit for each defect class should be defined. There should be limits for individual defects and for the sum of all defects within a defect class. Yields should also be monitored.

基于生产过程的趋势分析，应为每个缺陷类别定义限值。应对单个缺陷以及同一缺陷类别内所有缺陷的总和设定限值。同时还应监控收率。

 

Limits should be defined on process history (overall maximum reject rate, rate per defect / particle category) and should reflect and reference the process capability index (Cpk) for the process step.

限值应根据工艺历史（整体最高拒收率、每个缺陷/颗粒类别的发生率）来定义，并应反映和参考该工艺步骤的过程能力指数（Cpk）。

 

Action limits must be determined product specific, based on production history. In case there is no previous experience, typical action limits for individual defects are for example:

行动限值必须根据生产历史按具体产品确定。若没有以往经验，单个缺陷的典型行动限值例如：

 

Critical defects: 0.5 % to 1 % *

关键缺陷：0.5%至1% *

 

Previous defects: 1 % to 3 %

既往缺陷：1%至3%

 

Major defects: 3 % to 5 %

主要缺陷：3%至5%

 

Minor defects: 5 % to 10 %

微小缺陷：5%至10%

 

*For critical defects, the severity limit (GMP issues such as sterility-impairing defects (e.g., turbidity, cracks or mix-ups) indicating GMP is 0, triggering an investigation.

对于关键缺陷，严重性限值（如影响无菌性的缺陷（例如浑浊、裂缝或混淆）等GMP问题，表明GMP符合性为0，需启动调查。

 

Typical action limits can also be based on specific defects (e.g. particles) instead of using the categories critical, major and minor.

典型行动限值也可基于特定缺陷（例如颗粒），而非使用关键、主要和次要这些类别。

 

Setting alert limits may be a reasonable e.g. to identify a production specific problem as early as possible.

设定警戒限值可能是合理的，例如尽早识别特定生产问题。

 

According to ASTM E2658-12 (Standard Practice for Use of Control Charts in Statistical Process Control), control limits for trending should be calculated from process data and not be based on fixed specification limits. However, the evaluation should optimally be based on at least 30 representative data points of the process. This would require preliminary control limits to be defined based on experience prior to the first calculation deriving from measured data points.

根据ASTM E2658-12《统计过程控制中控制图的使用标准实践》，趋势控制限值应根据工艺数据计算，而非基于固定规格限值。不过，评估应最优地基于工艺的至少30个代表性数据点。这就要求在根据测量数据点进行首次计算之前，根据经验预先定义初步控制限值。

 

If a batch exceeds a critical limit, the reason for this should be investigated. Batches exceeding the acceptance limits for trending limits should also trigger the company’s failure investigation process.

若某批次超出关键限值，应调查其原因。超出趋势限值接受标准的批次也应触发公司的失败调查流程。

 

Once the root cause has been identified and the inspection method is suitable for sorting out the defects causing the problem, the batch can be re-inspected. Re-inspection should never be performed without prior investigation. It has to be assessed whether the inspection method used in the initial inspection may not be suitable for re-inspection. E.g., if an automated test method used in identifying certain defects in the first run, it is likely to fail also in a second run. The decision on the re-inspection method should be made by an authorised and qualified person.

一旦确定根本原因，且检查方法适用于挑出导致问题的缺陷，可对批次进行复检。未事先调查不得进行复检。必须评估初始检查中使用的检查方法是否不适用于复检。例如，若某自动化测试方法在首次运行中用于识别某些缺陷，很可能在第二次运行中也会失败。复检方法的决定应由批准且受权的人员做出。

 

When frequent re-inspection must be performed, a failure investigation should be initiated with the aim to improve the sensitivity of the primary inspection process or the manufacturing controls to prevent defects in the upstream process as determined by root cause analysis.

当必须频繁进行复检时，应启动失败调查，目的是提高初始检查过程的敏感性或制造控制措施，以防止上游过程中出现缺陷（由根本原因分析确定）。

 

Re-inspection of rejected containers should not be performed.

不得对拒收的容器进行复检。

 

NOTE:

注：

 

“Grey Channel” for fully automated inspection systems: Defining a “grey eject channel” in automated inspection may be useful to separate containers for which the inspection result is not clear. From a technical point of view, a “grey channel” is also meaningful in case of e.g., machine stops, when it is uncertain whether a unit has been fully inspected according to procedure or not.

全自动检查系统的“灰色通道”：在全自动检查中定义“灰色剔除通道”可能有助于分离检查结果不明确的容器。从技术角度来看，在例如设备停机的情况下，当不确定某单元是否已按程序完成全部检查时，“灰色通道”也具有意义。

 

Examples for the Grey-Channels:

灰色通道示例：

 

Air bubbles: Air bubbles might be a reason for an unclear inspection result. Camera systems cannot distinguish between particular matter and air bubbles. Therefore re-inspection of containers from example, time reduces the number of air-bubbles, which reduces the false reject rate whilst maintaining a more stringent machine set-up.

1. 气泡：气泡可能是导致检查结果不明确的原因。摄像系统无法区分颗粒物和气泡。因此，对容器进行复检（例如，时间会减少气泡数量，从而在保持更严格的设备设置的同时降低误拒率）。

 

Other defects in the grey channel: from a technical point of view some small defects (e.g. small scratches) should be re-inspected manually if the inspection system is not able to differentiate predefined characteristics, for example due to ambiguities caused by the intrinsic characteristic of the product (air bubbles) at the time of inspection. The feasibility is shown during the validation.

2. 灰色通道中的其他缺陷：从技术角度来看，若检查系统无法区分预定义特征（例如，由于检查时产品的固有特征（气泡）导致的歧义），某些小缺陷（例如小划痕）应进行人工复检。其可行性在验证期间得到证明。

 

Objects in the grey channel usually do not require more than one re-inspection. Trending is done over the whole batch after the objects have been classified as good or bad.

灰色通道中的物品通常不需要多次复检。在物品被分类为合格或不合格后，对整批进行趋势分析。

 

8 Batch Certification/Release

8 批次认证/放行

 

For the release decision two criteria need to be evaluated:

对于放行决策，需评估两个标准：

 

Trending analysis of the 100% batch inspection (see chapter 7) and

1. 100%批次检查的趋势分析（见第7章），以及

 

The result of the AQL manual inspection.

2. 可接受质量水平（AQL）人工检查的结果。

 

The results of 100% visual inspection trending, done as part of manufacturing process, are an integral part of batch documentation, specifying the types of defects found (fibre, turbidity, crack, etc.) as well as a classification of the defect classes such as critical, major or minor. Acceptance criteria should be pre-defined for at least the defect classes defined from all defects found during the 100% inspection process (see above). For automated inspection, these classifications needs to be done on a technical level (side-wall defect, crimping defect,...) and cannot be done using the classification such as critical, major or minor (see above).

作为生产过程一部分开展的100%目视检查趋势分析结果，是批次文件的组成部分，需明确发现的缺陷类型（纤维、浑浊、裂缝等），并对关键、主要或次要等缺陷类别进行分类。至少应针对100%检查过程中发现的所有缺陷所定义的缺陷类别预先确定接受标准（见上文）。对于全自动检查，这些分类需在技术层面（侧壁缺陷、压塞缺陷……）进行，不能使用关键、主要或次要等分类（见上文）。

 

For the AQL manual inspection, a randomized sampling out of the accepted containers coming from 100% inspected batch should be performed according to a pre-determined AQL procedure. AQL manual inspection may be carried out by production staff under a quality oversight or the quality unit.

对于AQL人工检查，应根据预先确定的AQL程序，从100%检查过的批次中已放行的容器中随机抽样。AQL人工检查可在质量监督下由生产人员执行，或由质量部门执行。

 

For release of the batch, the minimum AQL is typically:

对于批放行，典型的最低AQL要求为：

 

Critical: 0 defects within the AQL samples

关键缺陷：AQL样品中无缺陷

 

Major: ≤ 0.65 AQL

主要缺陷：≤0.65 AQL

 

Minor: ≤ 4.0 AQL

微小缺陷：≤4.0 AQL

 

If an AQL limit is exceeded, the whole considered-to-be-acceptable batch should be re-inspected 100% followed by a second AQL manual inspection with tightened AQL limits. This process is usually not repeated several times. Tightening of AQL limits can be considered and is possible by two ways: Stay on the AQL sample size and use the next (tighter) AQL limit- OR: Stay on the AQL limit and use the next (higher) AQL sample size.

若超出AQL限值，应对整批被视为可接受的批次进行100%复检，随后采用加严的AQL限值进行第二次AQL人工检查。该过程通常不会重复多次。可考虑加严AQL限值，有两种方式可行：保持AQL样本量不变，使用下一个（更严格的）AQL限值——或：保持AQL限值不变，使用下一个（更大的）AQL样本量。

 

Particles found in AQL testing must be characterized and evaluated according to their nature. If characterization shows that the particle is not process-related the origin must be investigated and assessed prior to further actions. Particular attention during investigation should be paid to possible adulteration, sterility, or other cGMP-related issues of the affected batch.

在AQL测试中发现的颗粒必须根据其性质进行表征和评估。若表征显示颗粒与工艺无关，必须在采取进一步行动前调查并评估其来源。调查期间应特别关注受影响批次可能存在的掺假、无菌性或其他与现行良好生产规范（cGMP）相关的问题。

 

If the characterization shows that the particle violation is process-related, the number of units found in AQL must be within the given AQL limits. AQL limit violation of those particles triggers an investigation followed by a 100% reinspection of the batch. A second AQL test of the reinspected batch must then demonstrate successful particle clearance. Using tightened AQL limits should be considered. When particles are rated as major defects (according to USP <790>), and characterization shows that the particle is process-related while AQL limits are met, the batch can be approved for further processing. If AQL limits are exceeded again, a decision on further reinspection must be taken after the investigation has been closed (see figure).

若表征显示颗粒不符合要求与工艺相关，则AQL中发现的单元数量必须在给定的AQL限值内。这些颗粒的AQL限值超标会触发调查，随后对批次进行100%复检。复检批次的第二次AQL测试必须证明颗粒已成功清除。应考虑使用加严的AQL限值。当颗粒被评定为主要缺陷（根据USP <790>），且表征显示颗粒与工艺相关且AQL限值符合要求时，批次可获准进一步加工。若AQL限值再次超标，必须在调查结束后决定是否进一步复检（见图）。

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The number of AQL manual inspection steps should be evident in the batch documentation.

AQL人工检查的步骤数量应在批次文件中明确体现。

 

AQL manual inspection may be carried out in a separate area without time constraints for the inspectors.

AQL人工检查可在独立区域进行，对检查人员无时间限制。

 

The results of the 100% visual inspection trending, and the results of the AQL testing are part of the finished product release assessment that should embrace all relevant factors of the batch. After assessment by quality control or quality assurance, these data should be made available in an easily readable format to the Qualified Person, responsible for batch certification and release decision

100%目视检查趋势分析的结果以及AQL测试的结果是成品放行评估的一部分，该评估应涵盖批次的所有相关因素。经质量控制或质量保证部门评估后，这些数据应以易于阅读的格式提供给负责批次认证和放行决策的合格人员。

 

9 Concerns regarding distributed Product

9 关于已分销产品的关注事项

 

When concerns arise regarding particulate matter of product already distributed to the market, it is recommended to inspect several samples following a practical DIN ISO 2859 compliant sampling plan.

当对已分销至市场的产品中的颗粒物产生担忧时，建议按照符合DIN ISO 2859的实用抽样计划对若干样品进行检查。

 

As visual inspection for particulates is a probabilistic and not a deterministic process, sampling plans for non-critical defects with a limit of zero are not practical as an assessment tool and should be avoided.

由于颗粒物的目视检查是一个概率性而非确定性的过程，针对非关键缺陷且限值为零的抽样计划作为评估工具并不实用，应予以避免。

 

The inspection needs to be performed under the same conditions as the routine inspection was performed. The relative batch and sample size will determine the acceptance criteria, if these criteria are met by inspection of these samples, the batch can be considered essentially free of particles.

检查需在与常规检查相同的条件下进行。相关批次和样品量将决定接受标准，若对这些样品的检查符合这些标准，则可认为该批次基本无颗粒。

 

It is good practice to isolate particle(s) of any complaint sample and to determine the size and to characterize the nature of the particle(s) during investigation.

在调查期间，分离投诉样品中的颗粒，确定其大小并表征其性质，是良好的操作规范。

 

10 Definitions

10 定义

 

AQL

AQL

 

Acceptable Quality Limit, using ANSI/ASQ Z1.4 or ISO 2859-1, general inspection level II

可接受质量水平，采用ANSI/ASQ Z1.4或ISO 2859-1，一般检查水平II

 

CRI-Index:

CRI指数：

 

The Colour Rendering Index (CRI) is a unit of measure that defines how well colours are rendered by different illumination conditions in comparison to an ideal or natural light source. The Ra value uses only the first eight from the 14 test colours of the DIN 6169. Light sources have different Ra values, e.g. a white LED 80-95; fluorescent lamps 50-90.

显色指数（CRI）是一种度量单位，用于界定与理想或自然光源相比，不同照度条件下颜色的呈现效果优劣。Ra值仅采用DIN 6169的14种测试颜色中的前8种。光源具有不同的Ra值，例如白色LED为80-95；荧光灯为50-90。

 

Function testkit:

功能测试套件：

 

A functional 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 kit of more apparent defects such as big particles, cracked or empty containers.

每批检查前后使用的功能测试套件（系统适用性测试套件），用于证明全自动检查系统的功能。它可能包含简化的套件，其中有较明显的缺陷，如大颗粒、破裂或空的容器。

 

Particle:

颗粒：

 

A particle in the context of this paper means a readily visible particle with a diameter or span 150 μm or bigger that allows reliable detection (70% probability or higher) in a clear solution. Smaller, for example coloured or shiny particles may be visible down to a size of 50 μm or smaller and thus have also to be counted to the group of visible particles.

在本文中，颗粒指直径或跨度为150μm或更大、在澄清溶液中可可靠检查（概率70%或更高）的易见颗粒。更小的颗粒，例如有颜色或有光泽的颗粒，可能小至50μm或更小仍可见，因此也应计入可见颗粒组。

 

PQ

PQ

 

Performance qualification (PQ) is intended to confirm the capabilities of the machine to which extent a specific set of defects (qualification kit) is detectable. This test is conducted by inspecting the samples with the machine several times by finally calculating the detection rate which is the quotient of the number of detected samples by the total amount of samples in a specific category. Thus, the PQ serves to confirm the sensitivity of the machine.

性能确认（PQ）旨在确认设备对特定缺陷组（确认套件）的可检查程度。该测试通过用设备多次检查样品，最终计算检出率（检出样品数与特定类别中样品总数的商）来进行。因此，PQ用于确认设备的灵敏度。

 

PV

PV

 

Validation of the inspection system examines the entire inspection process (incl. two-stage AVI + SAVI/MVI, impact of light, etc.). This is part of the process validation (PV). PV shows the suitability of the process under routine conditions.

检查系统的验证检查整个检查过程（包括两阶段AVI + SAVI/MVI、光的影响等）。这是工艺验证（PV）的一部分。PV显示工艺在常规条件下的适用性。

 

Qualification kit:

确认套件：

 

A set of product specific containers with real product, A test kit of product specific containers with real product, containing randomly distributed defects. All known defects should be contained in the test kit. Any new defects should be added to the test kit after they have been identified. Units of tests kits for the manual inspection containing a defect should be marked or encoded invisibly. Obvious and clear readable numbers or letters should not be used. The kits should be cleaned after usage and routinely checked for defects at least every 6 months. There should be a logbook for each test kit.

一套装有实际产品的特定产品容器，是装有实际产品的特定产品容器的测试套件，包含随机分布的缺陷。所有已知缺陷都应包含在测试套件中。任何新缺陷在被识别后应添加到测试套件中。人工检查用的含缺陷测试套件单元应进行隐形标记或编码。不应使用明显且易读的数字或字母。套件使用后应清洁，并至少每6个月常规检查缺陷。每个测试套件应有一本日志。

 

Training kit:

培训套件：

 

A test kit used for the training of the operators of the manual inspection, to teach the possible defects. Similar to the qualification test kit but contains only containers with defects.

用于人工检查操作员培训的测试套件，用于讲解可能的缺陷。与确认测试套件类似，但仅包含有缺陷的容器。

 

Visual Inspection:

目视检查：

 

The process of sorting unacceptable units from acceptable units by human visual inspectors and/or through qualified equipment.

由人类目视检查人员和/或通过合格设备将不合格单元从合格单元中分拣出来的过程。

 

Fully automated visual inspection:

全自动目视检查：

 

The process of sorting unacceptable units from acceptable units by equipment (camera system). Detection and handling of units to be inspected is performed by equipment.

通过设备（摄像系统）将不合格单元从合格单元中分拣出来的过程。待检查单元的检查和处理由设备执行。

 

Fully automated (non-inline) visual inspection:

全自动（非在线）目视检查：

 

The process of sorting unacceptable units from acceptable units by equipment (camera system) after the batch production has been finished.

批次生产完成后，通过设备（摄像系统）将不合格单元从合格单元中分拣出来的过程。

 

In-line fully automated visual inspection:

在线全自动目视检查：

 

The process of sorting unacceptable units from acceptable units by equipment (camera system) parallel or at the same time of the batch production.

在批次生产的同时，通过设备（摄像系统）将不合格单元从合格单元中分拣出来的过程。

 

 

本文由广州佳誉医疗器械有限公司/佛山浩扬医疗器械有限公司联合编辑