Comments to the 2020 closing and 2021 update by CEO Axel Sjöblad.
Poster presented at SOT 2021
Joshua Schmidt, Ron Brown and Rose-Marie Jenvert
SenzaGen Inc., Raleigh, NC, USA, Risk Science Consortium LLC, Arnold, MD, USA, SenzaGen AB, Lund, Sweden.
- The chemical space of compounds tested in GARD closely approximates the chemical space of compounds known to be released from medical device materials.
- GARDskin is able to predict the skin sensitization potential of compounds released from medical device materials with a high degree of sensitivity and specificity, including: metals, lipophilic compounds and pre/pro haptens.
Medical device toxicology is undergoing an exciting evolution; transitioning from a process that largely relied on the results of animal testing to evaluate the biological safety of devices in patients to one which is increasingly focused on the use of in vitro methods for the safety assessment of device materials.
Recently, in vitro methods to assess endpoints such as skin irritation and pyrogenicity have been validated and proposed for medical device testing, but a method to assess the potential for device-related skin sensitization to occur has not been sufficiently qualified. A number of in vitro skin sensitization test methods have been shown to have acceptable predictive ability for known skin sensitizers with structures that span a broad range of chemical classes, but the predictive ability of these methods has not been specifically evaluated using compounds typically found in materials used to manufacture medical devices. As a result, the need exists to qualify in vitro methods to assess the skin sensitization of compounds that may be released from medical devices, taking into account the applicability domain of known or potential skin sensitizers, including metals.
To address this challenge, the predictive ability of the GARD assay has been evaluated using a dataset of compounds known to be released from device materials. Against these data, the assay correctly predicted 19 out of 21 lipophilic and pre-/pro-hapten compounds (90.5% accuracy), with one false positive (95.2% sensitivity) and one false negative (95.2% specificity) being predicted, thus increasing the confidence in use of this in vitro assay to assess the skin sensitization potential of medical devices. Furthermore, we have also demonstrated that the GARD assay correctly predicts the skin sensitization response of nickel and cobalt salts (sensitizers) and a zinc salt (non-sensitizer). Overall, our data support the use of the GARDskin Medical Device assay as an in vitro alternative for the in vivo methods (e.g., GPMT, LLNA) that are typically used to assess skin sensitization as part of the biological safety assessment of medical devices.
Poster presented at SOT 2021
Henrik Johansson, Robin Gradin, Andy Forreryd, Joshua Schmidt
SenzaGen AB, Lund, Sweden. SenzaGen Inc., Raleigh, NC.
- As an adaptation from the GARDskin assay, GARDskin Dose-Response is suitable for quantitative skin sensitizing potency assessment of chemicals.
- The experimental readout, referred to as cDV0, corresponds to the lowest dose required to elicit a positive response in GARDskin. As such, experimental protocols are analogous to the LLNA, in which the cDV0 corresponds to the EC3-value.
- The cDV0 may be used to directly monitor sensitizing potency, or further used to extrapolate LLNA EC3-values, estimation of Human potency categories, or CLP 1A/1B classifications.
Proactive identification and characterization of sensitization hazards are central aspects of risk assessment of chemicals. Current legislations and trends in predictive toxicology advocate a transition from in vivo methods to non-animal alternatives, with a number of methods for hazard assessment of skin sensitizers currently available. However, non-animal methods capable of providing quantitative assessment of sensitizing potency are currently lacking.
The GARDskin assay is a next-generation in vitro assay for hazard assessment of skin sensitizers, currently progressing towards regulatory acceptance. Recently, the GARDskin Dose-Response (DR) testing strategy was introduced, in which test chemicals are evaluated by the GARDskin assay in a titrated range of concentrations, in order to investigate the dose-response relationship between GARDskin classifications and test chemical concentration. As such, it provides a quantitative estimation of sensitizing potency, referred to as cDV0, which corresponds to the least required dose able to generate a positive response in the GARDskin assay. The cDV0 value obtained for a test chemical may be viewed as an analogue to the LLNA EC3 value, based on which further hazard characterization and risk assessment may be performed. Statistically significant correlation between the GARDskin DR cDV0 and the LLNA EC3, as well as with human No Expected Sensitization Induction level (NESIL) estimations has been confirmed, thus enabling direct extrapolation between the different metrics.
Here, we further introduce the GARDskin DR protocols, as proposed in a standardized testing strategy. By studying a concentration range of 6 concentration points titrated from the experimentally derived GARD input concentration in biological duplicates, a test chemical-specific cDV0 is established by linear interpolation. We illustrate how these results can be used on their own to facilitate direct potency-associated ranking of test chemicals. Furthermore, we demonstrate how obtained cDV0 values can be extrapolated to LLNA EC3 values with a 95% confidence interval, thereby also facilitating potency-associated subcategorization of test chemicals according to UN GHS classification criteria. Lastly, we illustrate how results generated with GARDskin DR can be directly incorporated into existing strategies for Quantitative Risk Assessment using an entirely in vitro setup.
SenzaGen had a busy program at SOT 2021. To highlight our expanding capabilities in in vitro skin toxicology, we took part in several activities and presented our novel assays for quantitative skin sensitizing potency assessment and medical device testing.
Exhibitor Hosted Session: Dose-response for predicting skin sensitization potency
Listen to SenzaGen’s Chief Scientist Dr Henrik Johansson presenting the latest development on GARD™skin Dose-Response, our novel in vitro assay for quantitative skin sensitizing potency assessment:
Workshop: Applicability domains and future of non-animal tests for skin sensitization
Learn from Dr Andy Forreryd how GARD™ and other in vitro assays can be used to fill data gaps in sensitizing hazard and potency assessment of chemicals:
Posters by SenzaGen and jointly with Corteva
Quantitative Sensitizing Potency Assessment Using GARD™skin Dose-Response| Request a copy
GARD™skin and GARD™potency: A Proof-of-Concept Study to Investigate the Applicability Domain for Agrochemical Formulations| View abstract
🏅 MDCPSS Best Overall Abstract Award Winner🏅
Applicability Domain of the GARD™skin Medical Device Test for In Vitro Skin Sensitization Testing of Medical Devices| Request a copy
At this year’s Society of Toxicology annual meeting SenzaGen’s in vitro Medical Device test method was awarded the Best Overall Abstract Award in the Medical Device and Combination Product Specialty Section.
Joshua J. Schmidt, Ph.D.
Rose-Marie Jenvert, PhD
Please come join us for discussions at the poster presentation
March 24 | 11:15am – 1:00pm EDT | 16:15-18:00 CET
In this interview CEO Axel Sjöblad comments the 2020 year-end report, ongoing projects, and the way forward.
SenzaGen’s sales during the full year 2020 tripled compared to 2019. Listen to CEO Axel Sjöblad commenting the 2020 performance in today’s conference call.
Thanks to all who attended our webinar ‘Why choose GARD for skin sensitization testing?’ last week. If you were not able to attend live, and wish to watch it, you can now access the webinar’s recording!