*3.2. Practicability*

Findings of the practicability assessment are summarized in Table 1.

**Table 1.** Assessment of the practicability for the different locations. For each criteria, a subjective three level scoring system (positive, neutral and negative assessment) comparing the three groups was applied.


*Ease of preparation:* For patch application on the outer surface of the ear, group 1 needed a moderate effort to clip and disinfect the skin. Compared to the outer surface of the ear, the inner surface (group 2) needed minimal effort to clip due to almost no hair growth. However, it took longer to degrease the skin. Group 3, with the patch located on the neck, showed the highest density of hair growth combined with very thin hair. As a result, even with another more powerful clipper, it took longer to clip the fur in this location. Additionally, fighting wounds were discovered in this location while clipping, which made it hard to place the patch in exactly the same position on each rabbit avoiding these skin lesions.

*Quality of patch adhesiveness* was comparable in all groups—no difference could be noticed.

*Ease of daily checks:* Animals of group 1 were the easiest to check, as the outer surface of the ear was promptly visualized. Tape loosening could be seen without manipulation. In contrast, in group 2 loosening of the tape and patch underneath could only be noticed while handling the rabbit. Group 3 differed from the other groups as a check of the patch was only feasible while holding the rabbit, as the patch on the neck resulted covered by the surrounding fur.

*Occurrence of undesired patch detachment:* Patch loosening in terms of detaching edges occurred starting 48 h after patch application particularly in group 2 and 3 but also in one animal of group 1, 72 h after patch application. Signs of mild manipulation (scratching) of the tape by the rabbits could be observed in all groups suggesting some irritation engendered by the presence of the tape/ patch. While in group 1 manipulation lead to partial patch loosening in just one animal, detaching of the

patches occurred in 5 of 6 animals of group 2 and 3 of 6 in group 3. Obvious and strong manipulation of the tape covering the patch was visible in 2 of 18 animals namely in group 2 and 3.

*Ease of patch removal:* Patch removal 120 h after application was the easiest and most stress-free for the animals in group 2 due to greasy skin and just a few regrown hair at this location. In contrast, group 1 and 3 showed a high density of regrown fur, which made it painful and hard to remove the tape and the patch in all these animals.

*Skin condition after patch removal:* Group 2 showed no signs of skin reaction after patch removal, whereas in group 1 and 3, a diffuse erythema underlying the drug-delivery portion of the patches was recognized in all the animals (Figure 6).

**Figure 6.** Representative images of skin condition after patch removal (**left**: group 1, **middle**: group 2 and **right**: group 3).

No differences in general condition, food or water intake, body weight, defecation, coprophagy or temperature were noticed among the three groups.
