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Direct contact method with new technical steps essential to detect cytotoxicity of a volatile substance. Medical device quality assurance.

Girish K. Srivastava1,2, Maria T. Garcia-Gutierrez3, José Carlos Pastor1,2,4

  1. Instituto Universitario de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, Valladolid, Spain.
  2. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain.
  3. Vision R+D, Valladolid, Spain.
  4. Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Abstract

Medical devices need to pass ISO-recommended safety assessments before clinical use. Perfluorocarbon liquids (PFOs) are used in intraocular surgery. Recent cases of blindness have raised questions about the current cytotoxicity test methods applied for the safety assessment of PFOs. The study proposes to assess cell culture responses to different PFOs by applying a direct contact method incorporating a few new technical steps for testing volatile substances such as PFOs. Limitations of the current methods, extract dilution exposure and agarose overlay, were recorded. ARPE-19 cell cultures were prepared, and the direct contact and extract dilution exposure methods were performed for different PFOs. The agarose overlay method was performed partially. Results showed that for non-toxic PFOs, the ARPE-19 cell cultures showed different growth tendencies at 24 and 72 hours for PFOs from different manufacturers, while always maintaining cell viability ≥70%; however, the difference was not significant for PFOs from the same manufacturer. The toxic PFOs were detected as toxic, which the extract dilution exposure method failed to detect. Several limitations were found when applying the current cytotoxicity test methods. One crucial limitation was that it was unknown whether a quantity of PFO or toxic components of PFO reached contact with the cell culture, which was not the case with the new direct contact method. It detected non-toxic and toxic PFO lots that were manufactured differently. The study strengthens the argument that a direct cytotoxicity method with the new technical steps is essential for the safety assessment of volatile substances and for guaranteeing the safety of such medical devices.

Keywords: Medical device quality assurance, Direct contact method, Cytotoxicity, Volatile substances

References

  1. Becker, R.A., Janus, E.R., White, R.D., Kruszewski, F.H., and Brackett, R.E. (2009). Good laboratory practices and safety assessments. Environ. Health Perspect. 117, A482-483; author reply A483-484.
  2. Bentley, D. (1999). CE marking--what does it really mean? J. Tissue Viability 9, 11–15.
  3. Bollen, L.S. (2005). New trends in biological evaluation of medical devices. Med. Device Technol. 16, 10–15.
  4. Donawa, M. (2003). Review of the Medical Device Directive. Med. Device Technol. 14, 20–23.
  5. Donawa, M.E. (1997). Complying with US and European complaint handling requirements. Med. Device Technol. 8, 12–15.
  6. Eckardt, C., Nicolai, U., Winter, M., and Knop, E. (1991). Experimental intraocular tolerance to liquid perfluorooctane and perfluoropolyether. Retina Phila. Pa 11, 375–384.
  7. Helmus, M.N., Gibbons, D.F., and Cebon, D. (2008). Biocompatibility: meeting a key functional requirement of next-generation medical devices. Toxicol. Pathol. 36, 70–80.
  8. Lamph, S. (2012). Regulation of medical devices outside the European Union. J. R. Soc. Med. 105 Suppl 1, S12-21.
  9. Li, W., Zhou, J., and Xu, Y. (2015). Study of the in vitro cytotoxicity testing of medical devices. Biomed. Rep. 3, 617–620.
  10. Pastor, J.C., Coco, R.M., Fernandez-Bueno, I., Alonso-Alonso, M.L., Medina, J., Sanz-Arranz, A., Rull, F., Gayoso, M.J., Dueñas, A., Garcia-Gutierrez, M.T., et al. (2017). Acute Retinal Damage After Using A Toxic Perfluoro-Octane For Vitreo-Retinal Surgery. Retina Phila. Pa 37, 1140–1151.
  11. Peyman, G.A., Schulman, J.A., and Sullivan, B. (1995). Perfluorocarbon liquids in ophthalmology. Surv. Ophthalmol. 39, 375–395.
  12. Reeve, L., and Baldrick, P. (2017). Biocompatibility assessments for medical devices - evolving regulatory considerations. Expert Rev. Med. Devices 14, 161–167.
  13. Schuh, J.C.L. (2008). Medical device regulations and testing for toxicologic pathologists. Toxicol. Pathol. 36, 63–69.
  14. Simons, J.H., and Harland, W.J. (1949). Production of Fluorocarbons III. From Hydrogen Fluoride-Soluble Organic Substances. J Electrochem Soc 95, 55–59.

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