In 2013, Casas et al. (1) published a paper stating that skin irritation test of medical devices in rabbits could likely be replaced with 3D reconstructed human epidermis (RhE) models that are already validated and regulatory accepted for skin irritation and corrosion testing of chemicals and cosmetics.
Based on this work, ISO Technical Committee (TC) 194, which concerns the biological and clinical evaluation of medical devices, encouraged involved parties in further development of this method (2, 3, 4) and initiated Round robin study to evaluate the predictive ability of RhE models to correctly identify low irritation potential of medical devices (5). Three organizations prepared and provided in total more than 2000 positive and negative samples of medical devices polymers specifically for this study (6). In addition, human patch tests were performed with selected benchmarks to evaluate the agreement of the predictions between rabbits, human volunteers and the RhE models (7).
The results of the Round robin study conducted in 2016 and 2017 by 17 laboratories around the world, and several other scientific papers related to this outstanding project are now published in Toxicology In Vitro in a special issue dedicated to Medical Devices (8). Based on the results of this project, the Working Group 8 for Irritation and Sensitization of the ISO TC 194 on Biological and Clinical Evaluation of Medical Devices proposed working draft of ISO guideline 10993-23 for Determination of Skin Irritation of Medical Device Extracts using RhE models.
We all hope that once this new guideline is approved, that the use of rabbits for irritation testing of medical devices will end – just as what happened 10 years ago for cosmetics in Europe.
Literature:
In vitro human skin irritation test for evaluation of medical device extracts. Casas JW, Lewerenz GM, Rankin EA, Willoughby JA., Blakeman LC, McKim JM, Coleman KP (2013). Toxicol In Vitro. 27, 2175-2183.
Pre-validation of an in vitro Skin Irritation Test for Medical Devices Using the Reconstructed Human Tissue Model EpiDerm. Kandarova H, Willoughby JA, De Jong WH, Letasiova S, Milasova T, Bachelor M, Breyfogle B, Handa Y, De la Fonteyne L, Coleman KP. Toxicol In Vitro. 2018. February 8. Accepted for publication.
Assessment of test method variables for in vitro skin irritation testing of medical device extracts. Olsen D, Lee M, Turley A, Toxicology In Vitro. 2017 Nov 24. doi: 10.1016/j.tiv.2017.11.012. [Epub ahead of print]
SkinEthic™ RHE for in vitro evaluation of skin irritation of medical device extracts. Pellevoisin C, Videau C, Briotet D, Grégoire C, Tornier C, Alonso A, Rigaudeau AS, Bouez C, Seyler N., Toxicol In Vitro. 2018 Jan 13. doi: 10.1016/j.tiv.2018.01.008. [Epub ahead of print]
Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts. De Jong WH, Hoffmann S, Lee M, Kandárová H, Pellevoisin C, Haishima Y, Rollins B, Zdawczyk A, Willoughby J, Bachelor M, Schatz T, Skoog S, Parker S, Sawyer A, Pescio P, Fant K, Kim KM, Kwon JS, Gehrke H, Hofman-Hüther H, Meloni M, Julius C, Briotet D, Letasiova S, Kato R, Miyajima A, De La Fonteyne LJJ, Videau C, Tornier C, Turley AP, Christiano N, Rollins TS, Coleman KP., Toxicol In Vitro. 2018 Jan 8. doi: 10.1016/j.tiv.2018.01.001. [Epub ahead of print]
Preparation of Irritant Polymer Samples for an In Vitro Round Robin Study. Coleman KP, Grailer TP, McNamara LR, Rollins BL, Christiano NJ, Kandárová H, De Jong WH. Toxicol In Vitro. Jan. 22, 2018. doi.org/10.1016/j.tiv.2018.01.018 [Epub ahead of print]
Evaluation of the Medical Devices Benchmark Materials in the Controlled Human Patch Testing and in the RhE In Vitro Skin Irritation Protocol. Kandárová H, Bendova H, Letasiova S, Coleman K.P, De Jong WH and Jírova D. Toxicol In Vitro. 2018. February 8. Accepted for publication.
Reconstructed human epidermis models for irritant testing of medical devices. Coleman K.P, De Jong WH, Blaauboer BJ. 2018 Editorial. Available online 31 January 2018. doi.org/10.1016/j.tiv.2018.01.014