Abstract
Miniature pigs are an established preclinical model for subcutaneous (SC) drug administration; however, research on the direct translatability of this model is limited. This post hoc analysis of preclinical and clinical data assessed the translatability of performance characteristics of a high-volume auto-injector (HVAI) and SC injection site outcomes from the miniature pig model to humans. An HVAI was developed to subcutaneously administer 10 mL of an antibody solution at a targeted delivery time of ~ 30 s. These rapid, high-volume injections were facilitated by co-administration with recombinant human hyaluronidase PH20. The HVAI was assessed in previous preclinical studies in miniature pigs and in a Phase I clinical trial using the same devices (syringe pump and HVAI), test solution, and injection hardware, facilitating direct comparison between injection outcomes. Injection duration and injection site outcomes (swelling, induration, erythema, back-leakage) were measured in all studies. Injection force measurements with the syringe pump in pigs versus humans allowed for the calculation of a scaling factor to model injection duration in humans (90.8%) which was used to estimate an injection time of 27.5 s with this specific HVAI configuration. Observed injection duration between the two species were similar and not statistically different (30.0 s vs 27.9 s; p = 0.17). Swelling and induration were more significant in pigs than in humans (p < 0.01), while erythema scores tended to be higher in humans than in pigs (p < 0.05). Collectively, the miniature pig is a translatable model for subcutaneous injection that can generate useful predictions of injection times in human studies and de-risk clinical trials. Graphical abstract