Natural Defects Positive Control

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.