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

Girish K Srivastava 1,2, Maria T Garcia 3, José Carlos Pastor 1,2,4

1.     Instituto Universitario de Oftalmobiologia 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 Clinico Universitario de Valladolid, Valladolid, Spain


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

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

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Ms. Ref. No.: AllBios-A0101004     Reviewer 1   Reviewer 2
Received: 01072017
Accepted: 02122017
Article in Press: 03122017 
Published Online: 18122017

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