ECA Regulatory Interpretation: Frequently Asked Questions in Visual Inspection of Parenterals

In August 2026, ECA released the new version of "Frequently Asked Questions in Visual Inspection of Parenterals" (hereinafter referred to as the "Q&A guide"). It has once again brought the long-accumulated practical problems in the field of visual inspection of injections to the focus of industry attention.

The Q&A guide compiles and sorts out the problems repeatedly encountered by the industry in the actual production, verification and quality management processes. ECA also made it clear that the new version of the document integrates and revises the previous version of the Q&A and adds new questions that have been repeatedly raised in training and industry conferences in recent years.

Q&A Guide Focuses On 9 Topics

1｜Manual Inspection

2｜Automated Visual Inspection

3｜Qualification / Validation / Re-qualification AVI Systems

4｜Test Sets

5｜AQL Testing AQL

6｜Defect Categorisation

7｜Special Products

8｜Regulatory Affairs

9｜Process Control / SPC / Trending

4 Test Sets

4.1What are the differences between the qualification test set, the particle test set (Knapp test), and the function test set?

The three test sets serve different purposes:

• Function test set: Used for routine functional testing before batch inspection (and preferably after batch completion) to confirm correct system functionality. It typically contains easily detectable defects and is not intended to challenge the detection capability of the inspection system.

• Qualification test set (non-particulate defects): Used during performance qualification to demonstrate the detection of deterministic defects (e.g. missing stoppers or cosmetic defects). Qualification may be performed against predefined acceptance criteria and therefore does not necessarily require the inclusion of conforming units.• Particle test set (Knapp test): Used during performance qualification to demonstrate particle detection capability. Since particle detection is typically evaluated by man-machine comparison, the set contains both particulate defects and conforming units to allow comparison of the overall inspection performance.

4.2 Should qualification and function test sets be prepared artificially or should they represent real production defects?

Both approaches are acceptable. Whenever possible, test sets should contain representative defects originating from the manufacturing process, as these best reflect real production conditions. Where this is not feasible, artificially prepared defects may be used, provided they are representative of the expected defect characteristics.

Test sets may be prepared either in-house or by specialized external providers. However, product- and process-specific defects should be representative of the manufacturing process and appropriately justified.

4.3 What aspects should be considered when assessing artificially created test kits, and how should their suitability be justified?

Artificially created test kits are often used when representative production samples are unavailable, technically unsuitable, or cannot be obtained in sufficient quantity for qualification, training, or evaluation purposes.

Their suitability should be assessed based on the inspection technology used and the required level of representativeness. Artificially created defects and conforming units should exhibit optical, physical, and mechanical characteristics comparable to those of the real product under routine inspection conditions.

For AI-based inspection systems, higher requirements regarding representativeness may apply, as these systems often utilize very subtle features and characteristics to distinguish between acceptable and defective units. For example, a genuine lyophilized cake with crystalline reflective properties can generally be distinguished from a matte plaster-based imitation if these differences are visible in the image data.

If artificially created defects differ in relevant characteristics—such as texture, reflectivity, contrast, size, movement behaviour, or other optical or physical properties—there is a risk that the neural network learns features introduced by the artificial manufacturing process rather than the actual defect itself. Likewise, particle detection may be influenced by factors such as viscosity, turbidity, fill height particle size, or particle contrast. These factors should therefore be considered when assessing the suitability of artificially created test kits and may also affect the performance of conventional rule-based inspection systems.

Conventional rule-based systems are generally less susceptible to such effects because they evaluate predefined image features rather than learning complex representations. Although these approaches are often less selective and may be less suitable for highly challenging inspection tasks, they typically demonstrate greater robustness against variations or realism drifts within artificially created test kits.

Consequently, the suitability of artificially created test kits should always be justified and documented with regard to the inspection technology and the intended application. The decisive criterion is not whether defects are artificially created or taken from routine production, but whether the test kit reliably reproduces the behaviour of the final drug product under the selected inspection strategy.

4.4 How should test sets be maintained throughout their lifecycle?

Test sets should be managed under a defined lifecycle programme to ensure that they remain representative and fit for their intended use. Individual samples may be replaced as required (e.g. due to damage, ageing, or expiry). Some defect types may remain suitable for many years (e.g. bad crimping), whereas others (e.g. particles or contaminated samples) may change over time and therefore require more frequent replacement.

Where appropriate, qualification and training kits should be updated to include newly identified productor process-specific defects to ensure continued representativeness.

All test sets should be periodically reviewed (at least annually) and formally released following successful review. In addition, their integrity and suitability should be verified before use, where appropriate. The review, any replacements, and the release of the updated test set should be documented in accordance with the site's quality management system.

4.5 What should a compliant inspection test set contain?

A compliant inspection test set should contain representative defect samples covering all relevant defect categories together with a sufficient number of representative non-defect units. The composition of the test set should be appropriate for its intended purpose (e.g. training, qualification, or routine functional testing) and allow a meaningful assessment of inspection performance.

As a practical example, qualification test sets used for manual inspection or man–machine comparison should predominantly consist of non-defect units, with the proportion of defect units typically limited to approximately 10% of the total test set in order to minimize inspection bias. Typically, around 20–30 representative defect samples per defect category are included for qualification purposes, whereas routine function test sets may contain fewer samples. Each defect category should cover the expected variability of the defect. For example, a crack category should include defects of different lengths, orientations, and locations, while scratches or poor crimping should represent different severities and appearances rather than only a single characteristic example. The exact composition should always be justified according to the intended application, inspection methodology, and required statistical confidence.

Test sets should be blinded and randomized, where appropriate, to prevent memorization and bias. They should remain representative of the current product and manufacturing process and be maintained in accordance with the defined lifecycle programme.