EU-NETVAL is a EURL ECVAM network of specialised laboratories located in the EU member states.
EU-NETVAL's mission is to provide support for EURL ECVAM validation studies to assess the reliability and relevance of alternative methods that have a potential to replace, reduce or refine the use of animals for scientific purposes.
EURL ECVAM coordinates EU-NETVAL and works closely with the Commission's Directorate-General for Environment to facilitate interaction with the National Contact Points for the implementation of Directive 2010/63/EU on the protection of animals used for scientific purposes.
EU-NETVAL was set up by EURL ECVAM in response to the provision of Directive 2010/63/EU on the protection of animals used for scientific purposes which requests that EU Member States assist the European Commission in the validation of alternative methods. Currently there are a total of 35 members of EU-NETVAL, selected against pre-defined eligibility criteria and endorsed by the National Contact Points.
The Terms of Reference for EU-NETVAL detail the legislative anchor, the establishment of the network and the maintenance of its membership, tasks of network members and of EURL ECVAM in support of validation studies, the allocation of tasks to members and the financing of the network activities.
The current network holds a range of expertise and competences and includes laboratories experienced in advanced in vitro procedures, test systems and measurement techniques which are considered important to address specific aims and objectives identified in EURL ECVAM's strategies to achieve Three Rs impact in different areas of regulatory safety testing.
Activities of EU-NETVAL
- Validation of the Transcriptional activation assay for detection of androgenic activity of chemicals (AR-CALUX) in vitro method
[collapsed]In view of developing an OECD Test Guideline (TG) for Androgen Receptor Transactivation Assays (ARTAs), EURL ECVAM carried out a validation study of the in vitro method AR-CALUX. This method is a reporter-based assay where osteosarcoma cells, stably transfected with a human androgen receptor, will express luminescence when presented with chemicals that have (anti)androgenic potential. The in vitro method was submitted by the Dutch company BioDetection Systems (BDS).
From EURL ECVAM's network of specialised laboratories, EU-NETVAL, three facilities (Sweden, UK and France) were selected to participate in this validation study as well as the test method developer. A Validation Management Group was established to provide oversight on the study. EURL ECVAM has carried out an experimental assessment of the method, conducted a GLP study in order to refine the in vitro method AR-CALUX and establish transfer criteria and provided training for the three participating facilities at the JRC laboratories in Ispra. The three phases of the validation study (transfer phase, within and between laboratory reproducibility assessment, and, relevance assessment) are finalised. After peer review of the validation report by ESAC, an OECD TG will become availble that will include the AR-CALUX method and two additional ARTAs (developed by Japan and Korea). [/collapsed]
- Guidance Document on Good In Vitro Method Practices (GIVIMP)
[collapsed]To ensure regulatory acceptance and industry use of in vitro methods, good scientific, technical and quality practices should be used in the overall process from development to in vitro method implementation.
Coordinated by EURL ECVAM, the OECD developed a Guidance Document on Good In Vitro Method Practices (GIVIMP). It targets all key players involved in the process and covers in vitro method development, standardisation, validation, harmonisation and international acceptance. The guidance document is intended to support method developers and end-users working in academic, industry or government laboratories across all 36 OECD member countries and beyond.
EU-NETVAL has been involved in the drafting and review of the GIVIMP document and has a key role to play in applying GIVIMP when bringing in vitro methods from the developer to the end user.[/collapsed]
- Validation of thyroid hormone disruption methods
[collapsed]Concern over the potential for environmental chemicals to perturb hormone systems has led to the development and implementation of a number of OECD Test Guidelines for the screening and testing of endocrine disrupting chemicals. Although a number of methodologies have been developed to interrogate reproductive steroids, incorporation of test systems to evaluate disruptors of thyroid hormone signalling pathways has been limited, owing largely to the complexity of the thyroid system.
EURL ECVAM has compiled a number of Thyroid Hormone Disruption (THD) in vitro methods with validation potential, based on the OECD scoping paper (OECD, 2014) and with input from THD meetings and workshops. This large set of methods has been used as the starting point for validation of selected in vitro THD methods for the identification of modulators of thyroid hormone signalling. The validation is being carried out in collaboration with EU-NETVAL to
- respond to some of the provisions of Directive 2010/63/EU
- generate in vitro method information that is reliable, relevant and based on current best quality and scientific practices
- to increase the European Commission's validation capacity of in vitro methods and
- to provide a laboratory network knowledgeable on the routine implementation of GIVIMP for regulatory use in human safety assessment.
Other laboratories and experts that have shown interest or have in depth knowledge on THD in vitro methods are involved.[/collapsed]
- EU-NETVAL survey on miniaturised Ames tests
[collapsed]An Expert Working Group (EWG) on the miniaturised Ames tests was established by the OECD which includes experts from different member states/countries. During its kick-off meeting in February 2017, the EWG decided to develop a survey in order to obtain better insights into:
(i) the amount of data available for the different miniaturised bacterial gene mutation tests and
(ii) the extent to which these data can ultimately be shared.
The information collected with this initial EU-NETVAL survey has helped to support the decisions of the EWG on further actions required for the assessment of the miniaturised tests. This initail survey has been followed with a request for actual data sharing by EU-NETVAL test facilities.[/collapsed]
- Annual EU-NETVAL meeting
[collapsed]EU-NETVAL holds an annual meeting of all members. The main objectives of the meetings include providing the members with updates on the current state of the network as well as the opportunity to discuss progress in the validation of in vitro methods, training and dissemination activities and other related developments. Three meetings have taken place since the establishment of the network, the summary records and agendas of which are provided along with the highlights of each meeting below.
- Updates on AR-CALUX in vitro method
- Updates on defined approaches and OECD Test Guidelines for the skin sensitisation in vitro methods
- Updates on genotoxicity and the potential regulatory use of the OECD work regarding the non-test Guideline method miniaturised Ames assay
- Updates on the EFSA and OECD collaborative efforts for assessing alternative methods to detect adverse effect induced by chemicals that affect the developing nervous system
- Updates on the status of the large scale EU-NETVAL validation study for the detection of thyroid hormone disrupting chemicals following up the OECD scoping document on the topic
- In knowledge exchange sessions EU-NETVAL test facilities and invited experts agreed on key issues and recommendations to be considered in aiding the translation of more sophisticated methods into the regulatory domain, with particular emphasis on:
- complex test systems (e.g. 3-dimensional tissue models or human induced pluripotent stem cells),
- complex test items (e.g. chemical mixtures, biomedical devices, nanomaterials) and
- complex measurement technologies (e.g. automated imaging and 'omics) and
- the importance of advancing and implementing Good In Vitro Method Practices (GIVIMP) during in-house validation of in vitro methods
- Updates on AR-CALUX in vitro method
- EU-NETVAL Survey on uptake of OECD Test Guideline skin sensitisation in vitro methods
- Share experiences and knowledge on specific in vitro methods for the detection of thyroid hormone disrupting chemicals.
- Experts were invited to host sessions addressing in vitro method definition and the practical management of test items and test systems
- Exchanging information on the process of in-house validation (GIVIMP)
- Potential regulatory use of non-Test Guideline methods such as the miniaturised Ames assay
- Open issues relating to Good In Vitro Method Practice
- New in vitro methods with validation potential
- Open issues relating to GIVIMP in preparation for the formal OECD process
- Knowledge sharing sessions on specific in vitro methods for the assessment of skin sensitisation potential
EU-NETVAL meeting 2015:
- Progress report on the AR-CALUX validation study
- Breakout groups to focus on specific areas of GIVIMP
- Sharing knowledge within EU-NETVAL through training: New methods and training needs and capacities
EU-NETVAL meeting 2014:
- Introduction to the network by EURL ECVAM, DG Environment, DG Enterprise and the OECD
- Planning of the AR-CALUX validation study
- Discussions on GIVIMP