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Showing posts with label Cytotoxicity. Show all posts
Showing posts with label Cytotoxicity. Show all posts

Suitability of ISO standards for medical device toxicity measurement

Girish K. Srivastava,

IOBA, Universidad de Valladolid, Valladolid, Spain

Abstract

ISO standards are applied at global level for quality assurance of medical devices. More specifically, ISO 16672 is used for ophthalmic implants and ocular endotamponades, and ISO 10993 for biological evaluation of medical devices. Recently, several clinical cases of perfluorocarbon liquid (PFCL), which are used in vitreo-retinal surgery, are reported from Chile, Spain, Switzerland, Holland, France, Italy, the Middle East and South America which has raised the questions on suitability of ISO standards for cytotoxicity measurement of PFCL. The investigation showed that ISO recommended extract indirect and agarose overlay method failed to detect the cytotoxicity of CE-marked PFCL samples, however a new direct method had detected the cytotoxicity of same samples confirming that clinical cases were due to PFCL toxicity. Therefore, this is very crucial to consider specific device-type situation for cytotoxicity test during applying the ISO standards for quality assurance. The PFCL is non-soluble and highly volatile substance. Similarly, intraocular gases, PFCL and silicon oils are completely different products and they may need different ISO standards for their quality measurement. 

Publication
Article ID: O0401019 (Suppl 1)   RA  Preprint
Received: 08/06/2022 
Accepted: 08/07/2022
Published: 08/08/2022

How to cite this paper 

 

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

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