Tag Archive for: In vitro biocompatibility testing

Joint poster with Sonova: Integrating NAMs into early-stage screening of novel materials

Case studies on the use of GARD®skin Medical Device for in vitro skin sensitization assessment


Presented at SOT and Eurotox 2024

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Conclusion

In conclusion, GARDskin Medical Device can detect signals from diluted and complex extracts of solid devices, with a sensitivity superior to animal methods.

This may significantly reduce the need of animal studies, improve the safety of the final product, and avoid potential costly late-stage failures.

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Abstract

The recent advancements in New Approach Methodologies enables the use of in vitro method for skin sensitization assessment as part of the biocompatibility testing for medical devices, which is conventionally tested in vivo. GARDskin OECD TG 442E is included in ISO 10993-10:2021 as the only OECD validated in vitro assay that is compatible with both polar and non-polar extraction vehicles, in line with ISO 10993-12:2021.  GARDskin Medical Device is an adaptation of the GARDskin assay, including a pre-sample treatment procedure where solid devices are extracted using both polar and non-polar vehicles.

The aim of this study is to demonstrate the benefits of using GARD for early-stage screening of materials intended for use in medical devices for assessing their skin sensitization potential. Results from two case studies were summarized in which GARDskin Medical Device was used for skin sensitization assessment. The first case study describes the testing of an acrylic-based device with a coating consisting of a UV-cured lacquer, where chemical analysis indicated the potential for skin sensitization. The second case study describes the testing of a polymeric material consisting of Cellulose-Acetate Propionate (CAP) with a plasticizer (Triethylene glycol bis (2-ethylhexanoate), CAS# 94-28-0), with contradictive existing in vivo (negative) and in vitro (positive) data.

In the first case study, the acrylic-based device induced a positive response in both polar and non-polar vehicles in GARDskin Medical Device and was thus classified as a skin sensitizer. It was hypothesized that the positive results may be due to inadequate curing of the lacquer within cavitary structures of the devices, where UV light exposure was insufficient. To confirm the hypothesis, follow-up testing was performed on an identical device, but without cavities, which was classified as non-sensitizer. In vivo data confirmed the outcome of the in vitro assay. Consequently, a modification was made in the manufacturing process to prevent the presence of lacquer in cavitary structures of the device.

In the second case study, the CAP material was positive in the non-polar vehicle and was thus labelled as a skin sensitizer. The plasticizer was identified as a potential culprit, considering a borderline negative result in LLNA (SI=2.97) and reported positive clinical data. To support the hypothesis a follow-up study was conducted using another adaptation of the GARDskin protocol capable of providing continuous potency predictions. The results classified the plasticizer as a weak contact allergen. As a result, a different material was selected for the device.

Keywords: Biocompatiblity, ISO 10993-10, GARDskin Medical Device, Skin Sensitization, ISO 10993-12

Using in vitro data for regulatory approval of medical devices according to MDR

Regulatory approval of medical devices according to MDR using in vitro data from GARDskin Medical Device for skin sensitization assessment


Presented at Eurotox 2023

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Conclusion

  • The GARDskin Medical Device assay is a novel method for assessment of skin sensitizing properties in leachables from solid materials, according to ISO 10993 standards.
  • Here, we demonstrate how GARDskin Medical Device data, combined with endpoint data from skin irritation and cytotoxicity testing, were successfully used in a data package for biocompatibility assessment of a novel medical device.
  • Following review by a notified body, an obtained CE-mark for the medical device Tinearity® G1 highlights unique opportunities to comply with the European Medical Device Regulation 2017/745 (MDR) using only in vitro data sources.

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Abstract

Skin sensitizers in medical device extracts are conventionally assessed in vivo, primarily using the Guinea Pig Maximization Test and the Buehler Occluded Patch Test. However, there is a shift in the medical device toxicology field towards an increased use of in vitro methods for the evaluation of the biological safety of medical devices. Recently, in vitro methods for the endpoints skin irritation and skin sensitization have been included in the ISO 10993 standard, what makes it possible to perform this testing in vitro. The GARDskin assay is one of the in vitro methods for assessment of skin sensitization described in ISO 10993-10 and is the first OECD TG 442 method that has been adapted to work with oil, the non-polar extraction vehicle often used in in vivo studies for testing medical devices.

Here we share an example of how in vitro testing results, including results from the GARDskin Medical Device assay, were submitted to obtain CE-marking according to the European Medical Device Regulation 2017/745 (MDR) for Tinearity® G1, an innovative tinnitus treatment medical device. Tinearity® G1 was classified as a non-sensitizer in both polar and non-polar extracts in the GARDskin Medical Device assay. This result was used together with in vitro cytotoxicity and in vitro skin irritation results as weight of evidence together with review of chemical data in the risk assessment and biological evaluation of the medical device.