Marisa Meloni ^1* Barbara De Servi ^1* Francesco Carriero ¹ Emmanuelle Simon O'brien ² Dounia Houamel ^2* Philippe Deruelle ^2,3 Vincent Castagné ^2*

• ¹ VitroScreen (Italy), Milano, Italy
• ² Biocodex (France), Compiegne, France
• ³ Department of Obstetrics and Gynecology, Montpellier University Hospital, France, Montpellier, France

Regulation (EU) 2017/745 on medical devices (MDR) has significantly modified the rules to be adopted for MD qualification and classification. New requirements imply to generate robust evidence on mechanism of action (MoA) that cannot be produced by existing common EU or ISO standards. Given as accepted, the concept of “case by case’’ a new evidence-based non-clinical approach to MD qualification has to be defined. In this work, an in vitro experimental approach is described to assess the physicochemical and mechanical MoA of two hyaluronic acid (HA)-based medical devices: Mucogyne® Gel and Mucogyne® Ovule for vaginal use. They both act as moisturizers and lubricants as well as healing adjuvant by promoting the continued moisture of the vulvovaginal area. The MoA of these two products has been demonstrated by using a 3D reconstructed human vaginal epithelium (HVE) model in homeostatic physiological state and in stressed conditions. Film forming and persistency properties were assessed on intact HVE tissues by caffein permeation assay and Lucifer Yellow (LY) localization on HVE vertical sections. Healing properties were assessed on injured HVE tissues by Trans Electrical Epithelial Resistance (TEER) measurements associated to histo-morphological analysis (H&E), and moisturizing efficacy was evaluated on HVE tissues cultured in dryness conditions by histomorphological analysis (H&E) and aquaporin 3 (AQP3) expression and localization by immunohistochemistry (IHC). On the same ‘dry’ HVE model the non-pharmacological action of the two products was addressed by CD44 (hyaluronic acid receptor) expression and localization. The results suggest that the in vitro evaluations can provide robust results on a human relevant experimental model for the intended use of the products and support clinical data with mechanistic information which may not be achieved with in vivo studies but are particularly important for product qualification. The results also have underlined a specific relative efficacy on the mechanisms investigated for Mucogyne® Gel and Mucogyne® Ovule in line with their different formulation type (respectively hydrophilic and lipophilic) influencing the action of the active ingredient HA. The present in vitro non-clinical evaluation of HVE combined with clinical investigation data: Mucogyne MDs provide significant benefits in various physiological or pathological situations including vaginal dryness.