SENS-IS | EURL ECVAM

Topic: Skin sensitisation

Test Method Number:

TM2011-11 (EU)

Short Name of TM:

SENS-IS

Year received:

2011

Responsible Organisation:

EURL ECVAM - European Union

General Comments:

Under external validation

Method Description

The SENS-IS assay is a patent-protected gene expression-based test method proposed to discriminate between skin sensitisers, non-sensitisers and skin irritants by analysing the expression in Reconstructed human Epidermis (RhE) of a panel of 65 genes grouped in one gene set for irritancy (IRR) and two (SENS-IS and ARE) for sensitisation. In addition, the test method allows the classification of sensitisers into potency categories on the basis of the concentration of chemical needed to induce a positive response.

A test substance is classified as sensitiser on the basis of the number of overexpressed genes (compared to solvent control) measured by qRT-PCR in Episkin RhE tissues. The biomarkers have been selected starting with data mining, followed by treatment with either sensitisers or irritants in the LLNA model, further refined using qPCR analysis of suction blisters on human volunteers sensitised to Nickel or fragrance mix in a controlled clinical trial, and...

The test system used is the commercially available EpiskinTM, a 3D RhE obtained by culturing adult human keratinocytes on a collagen substrate to permit their terminal differentiation and the reconstruction of an epidermis with a functional stratum corneum. According to the test submitter, this model can take account of skin metabolism and skin penetration and should be widely applicable to testing of chemicals, including pre and pro-haptens, solids and liquids.

Track Approval Status

Submission
Validation
Peer-review
Recommendation
Regulatory acceptance/Standards

Submission

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Date	Stage	Comment
Oct 2011	Receipt of presubmission	Presubmission (TPF) received.
Nov 2011	Assessment of presubmission	Submitter notified of SENS-IS presubmission assessment outcome and invited to send a full submission.
Sep 2012	Receipt of full submission	Full submission received in September 2012.
May 2013	Assessment of full submission	Additional information was requested by EURL ECVAM on 26/03/2013 and 16/05/2013.
Jun 2013	Receipt of revised full submission	Receipt of revised submission addressing EURL ECVAM comments.
Nov 2013	Assessment finalised	Assessment of revised full submission finalised. The submitter was invited to revise his full submission on successful completion of the external validation study he intended to conduct.
Jul 2016	Receipt of revised full submission	Revised full submission including validation study data received in July 2016. Additional information was requested by EURL ECVAM in September-November 2016 and October 2017, and received in November-December 2016 and November 2017, respectively. Additional data were also kindly provided by Cosmetics Europe in February 2017 to support the assessment of SENS-IS.
Jun 2018	Stopped	Assessment finalised and submitter informed of decision not to progress to peer review by ESAC at this stage. The evaluation highlighted some shortcomings that impeded EURL ECVAM from reaching a conclusion on the validity of the test method. The test submitter was invited to address all the identified issues in writing, eventually with a revised submission, so as to allow EURL ECVAM to consider if the test method can be progressed to peer-review by the ESAC. In addition, the SENS-IS is protected by patent, which may impede the development and validation of similar methods by third parties, currently a requirement at OECD level for the adoption of methods based on Intellectual Property Rights (IPR) as Test Guidelines in order to avoid commercial monopolies. The JRC (EURL ECVAM) is currently involved in an expert group set up by the OECD to discuss this matter but the deliberations are still on-going.
Dec 2018	Receipt of revised full submission	A revised submission was received. EURL ECVAM accepted this submission for assessment because previously identified IPR issues can now be considered under the terms of the recently published OECD Guidance Document No. 298 on the "Guiding Principles on Good Practices for the Availability/Distribution of Protected Elements in OECD Test Guidelines".
Jul 2019	Assessment of full submission	EURL ECVAM concluded that there are still shortcomings in the submission and the test submitter was invited to addess them in a revised submission. In addition, due to the overlap between the chemicals tested in the validation of the SENS-IS and the chemicals under discussion at OECD level in the context of the development of a Guideline on Defined Approaches (DAs) for skin sensitisation, the test submitter was advised to re-evaluate the predictive capacity of the SENS-IS once reference in vivo classifications are agreed internationally at the level of the DAs project.
Oct 2020	Receipt of revised full submission	Receipt of additional documents addressing EURL ECVAM comments. EURL ECVAM assessment of the submitted material ongoing.
Dec 2020	Assessment finalised	Assessment of the additional information provided finalised by EURL ECVAM. The decision to proceed with peer review by the EURL ECVAM Scientific Advisory Committee (ESAC) was communicated to the test submitter.

Validation

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Date	Stage	Comment	Documents/Links
Jul 2016	Finalised	Validation study was performed externally and not coordinated by EURL ECVAM. See Submission step.

Peer-review

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Date	Stage	Comment
May 2021	Ongoing	Ongoing
Oct 2021	Ongoing	After their initial review, the ESAC Working Group (WG) requested the test submitter to clarify aspects of the SENS-IS submission including making available additional evidence on the reproducibility of the method, if available. The test submitter addressed the ESAC WG request in written and provided new data on the reproducibility of the method. In addition, direct interaction between the ESAC WG and the test submitter was facilitated by EURL ECVAM.
Mar 2022	Stopped	The ESAC WG communicated to EURL ECVAM they were not in the position "to ensure a transparent, consistent and reliable peer review of the SENS-IS test method" due to the quality of the submitted SENS-IS data. As a consequence, EURL ECVAM decided to stop the ESAC peer review. The test submitter has the option to make a new submission to EURL ECVAM if the quality issues can be properly addressed.

Recommendation

Regulatory acceptance/Standards