|Questions & Answers regarding the OECD Test Guidelines Programme (TGP)
The answers included in this document are based on Guidance Document N°1 for the Development of OECD Guidelines for the Testing of Chemicals1, and on current practice. Procedures described can be changed provisionally or permanently with agreement of all countries. The time needed to develop and approve a new or revised Test Guideline is highly depending on countries’ effort to reach agreement.
The TGP produces draft Test Guidelines and other draft Test Guideline-related documents such as validation reports, validation peer review reports, background documents, detailed review papers, guidance documents. However, the Questions & Answers focus on the development of Test Guidelines.
What are OECD Test Guidelines?
OECD Test Guidelines are harmonized test methods included in the OECD Council Decision2 on Mutual Acceptance of Data. This means that “data generated in the testing of chemicals in an OECD Member country (or some non member economies3) in accordance with OECD Test Guidelines and OECD principles of Good Laboratory PracticeError: Reference source not found shall be accepted in other Member countries (or non member economies) for purposes of assessment and other uses relating to the protection of man and the environment”.
Test Guidelines, including any annex or appendix, are submitted to Council for adoption before their publication. All other documents produced by the TGP are published in the Series on Testing and Assessment after their declassification by the Joint Meeting.
Who oversees the TGP?
National Coordinators nominated by governments of member countries and by some non member economiesError: Reference source not found and the European Commission have a central position in the TGP. The Working Group of the National Coordinators of the Test Guidelines Programme (WNT) meets once a year and oversees the work of the TGP. The WNT reports to the Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology (Joint Meeting), which is the policy body overseeing the OECD Chemicals Programme.
Stakeholders from industry through the Business and Industry Advisory Committee, from animal welfare organizations through the International Council for Animal Protection in OECD Programmes, and as appropriate, from trade unions through the Trade Union Advisory Committee, and from environmental NGOs through the European Environmental Bureau, provide input but do not make final decisions.
What are the different stages of OECD Test Guideline development?
The different stages are as follows:
a) Submission of a project by a National Coordinator, the European Commission or the Secretariat, for inclusion in the TGP work plan: a standard project submission form (SPSF) must be used (see Section 1)
b) Validation and peer review: any test method should be validated before becoming an OECD Test Guideline (Guidance Document N°34 on the Validation and International Acceptance of New or Updated Test Methods for Hazard AssessmentError: Reference source not found). The validation is peer reviewed via a process agreed by the WNT (See Section 2)
d) Experts discussions and WNT agreement on the draft Test Guideline (see Section 3)
e) Adoption process from WNT approval to Council adoption (see Section 4)
1. Project submission for inclusion in the TGP work plan
SPSFs must be submitted for projects for a new or revised Test Guideline, or for other Test Guideline-related documents (e.g. guidance document, detailed review paper, and background document). SPSFs are assessed by WNT members who can (i) accept the inclusion of the project in the work plan, (ii) reject the inclusion of the project in the work plan, or (iii) request further information.
1.1 Who can submit formal projects?
Government via their National Coordinators, the European Commission, the Secretariat and any OECD programme (e.g. The Task Force on Biocides) can submit SPSFs. Other stakeholders can be associated with the projects submitter.
1.2 What information is required in the SPSF?
The SPSF should inform on the work plan for the project. In order to ensure the resources necessary to the development of a draft Test Guideline through its finalization, the SPSF should also inform on resources that will be provided by the lead country for the validation and development of the draft Test Guideline. Information on related regulatory needs and validation status, applicability and limitation of the methods is requested.
1.3 When should a formal proposal be submitted to the Secretariat?
A formal proposal to develop a draft Test Guideline can be submitted at any time, but not later than 2 months before the meeting of the WNT to be assessed at that meeting.
1.4 Who decides on inclusion of projects on the work plan?
The SPSFs are assessed by the National Coordinators, the European Commission and other stakeholders such as BIAC and ICAPO, but the decision to include a project in the work plan is made by the National Coordinators and the European Commission only.
1.5 What main criteria should be met to include a project in the work plan?
When the WNT assesses a SPSF, it is requested to respond to the following question: “Taking into account the project information, requested above, does this project meet the needs of the member countries for addition to the work plan of the Test Guidelines Programme?”
A project for an OECD Test Guideline is expected to be included in the work plan if at least two countries from different regions (North America, Europe, Asia-Pacific) consider that Test Guideline is useful.
1.6 What is an informal preliminary proposal or a preliminary SPSF?
It is possible to submit an informal preliminary proposal to gauge views of other countries on the project, before its formal submission. The WNT is informed that a new preliminary proposal is posted on the protected website. Any comment should be sent directly to the lead country. Preliminary proposals can be submitted by any stakeholder, e.g. industry, with a view to finding a lead country to take over the responsibility for the project.
2. Validation and validation peer review
2.1 Validation status
SPSFs for Projects for Test Guidelines can be submitted at different stages of validation of the test method: (i) ongoing pre-validation (ii) ongoing validation, or (iii) completed validation. The duration of the project is highly dependent on the validation status, which has to be clearly described in the SPSF.
If a SPSF for a project for Test Guideline is submitted after the method has been fully validated, the validation report and, if available, the validation peer review report, should be submitted to the Secretariat together with the draft Test Guideline, and these documents will be made available to the WNT.
If a project of the work plan is under validation by a country, the WNT should be regularly informed of progress, and any issue related to this validation should be reported. It is recommended that SPSF should be submitted after the pre-validation stage, when it can be expected that validation outcome of the method will allow the development of a Test Guideline.
2.2 Who is responsible for the validation of test methods before development of OECD Test Guidelines?
OECD involvement in the validation of test methods is variable as shown below by examples:
Example of test method validation for endocrine disruption mechanism
For methods to detect endocrine disruption, the validation is managed by a validation management group (VMG) on mammalian toxicity testing or a VMG on ecotoxicity testing, as appropriate. These two OECD experts groups, which report to the WNT, decide how laboratories in countries should conduct validation (e.g. number and identification of chemicals to be tested, reference chemicals, number of replicates, statistical interpretation of results, and criteria for positive or negative test results, etc). An Advisory Group on Endocrine Disrupters Testing and Assessment is requested to comment on the validation reports, and the WNT is requested to approve the submission of the validation to the Joint Meeting for declassification and publication in the Series on Testing and Assessment.
Given the high number of in vitro methods under development in the last years, methods are being validated by countries, and experts from these countries report on progress with the validation at the meetings of the VMG for non animal testing. Practically, this VMG comments and provides advice on the validation rather than manages the validation of the test methods.
Example of test method validation for ecotoxic effects
For simple methods for ecotoxicity testing (e.g., tests on invertabrates), one lead country (or a small group of lead countries) is responsible for the method validation and for providing a validation report. For more complex test methods, (e.g. test on birds or on fish embryo), specific expert groups manage the (retrospective) validation and decide how laboratories in countries should conduct experimental validation, if such an experimental validation is considered necessary by countries.
Example of test method validation for human health effects
In most cases, specific expert groups are established to manage retrospective validation of in vivo methods for toxicity testing (e.g. alternative method for acute inhalation toxicity). The first draft of a retrospective validation is usually developed by experts of the lead country or by a consultant.
For in vitro methods for toxicity testing, it is expected that most validation and peer review reports will be developed jointly by validation/peer review bodies (ECVAM/ICCVAM/JaCVAM) and submitted jointly by the European Commission, the United States and Japan; this should make the validation process more efficient, and prevent request for additional experimental work or statistical analysis.
2.3 How long is the validation process?
Duration of the validation work, after a SPSF has been submitted and a project accepted, depends on the complexity of the endpoint(s) to be tested and on the validation status of the test method at the time the project is submitted. If the method is still at the pre-validation stage, it may take more than 2 years to complete the validation process. For some test methods for endocrine disruption, two to three validation phases were necessary in the past to fulfill all validation criteria, taking sometimes several years. When appropriate data are already available, it is possible to conduct a retrospective validation, and one year may be sufficient for the validation.
2.4 What is the process for validation peer reviews?
The OECD Secretariat has recently organized a few independent peer reviews for endocrine disrupters screening methods, with consultants as peer review managers. International peer reviewers were proposed by National Coordinators and confirmed by the peer review managers. Peer review packages are posted on the public website for TGP. International independent peer reviews can also be organized by individual countries. Circulation of the validation reports to the WNT and peer review by national experts in countries or by OECD expert groups are considered appropriate for validation of simple test methods.
2.5 What is the follow-up to peer review reports?
Validation peer review reports are posted on the public website, accompanied by WNT agreement on the follow-up of the peer review report. The WNT may agree on recommendations from the peer review, e.g. to further work to complete validation, or to develop criteria or considerations, such as limitations of the test methods, which should be included in the draft Test Guideline.
3. WNT agreement on draft Test Guidelines
3.1 What is the process for WNT agreement on draft Test Guidelines?
The first version of a Test Guideline is usually developed by the lead country and sent to the WNT for comments. In most cases, an expert group is established after the first commenting round to address comments received from the WNT. These comments include compilations of comments from national experts and national positions prepared by National Coordinators, as well as comments from other stakeholders. The expert group meets once or several times, as appropriate. There is at least one commenting round. Usually, 2 to 3 commenting rounds are necessary before the submission of a draft Test Guideline to the WNT for approval. Comments are either technical comments (e.g. related to the validation or to performance criteria) or policy comments (e.g. related to animal welfare concerns).
3.2 Who responds to comments, and revises the draft Test Guidelines?
The Secretariat, in cooperation with the lead country or an expert group, responds to comments and revises the draft Test Guideline. Responses to technical comments are expected to be provided by the lead country or the expert group.
3.3 What is the time needed for WNT agreement once a draft Test Guideline is available?
The time mostly depends on the number and nature of comments received from governments via their National Coordinators, and from stakeholders, at each commenting round. It also depends on time taken by the lead country to respond to technical comments. For the first commenting round, National Coordinators usually have 2 months to collect comments from national experts and prepare a national position. For subsequent commenting round, National Coordinators usually have six weeks to respond. The time taken by lead countries to respond to technical comments varies widely with countries.
3.4 Is it possible for anyone to access the most recent draft Test Guideline?
Yes, each time a new draft is developed and available for WNT comments, it replaces the previous draft on the public website. Draft Test Guidelines are used in some cases by industry or governments. On the public website, warning introduces the draft Test Guidelines: “Draft Test Guidelines are not part of Mutual Acceptance of Data. Please consult with National Authorities before using draft Test Guidelines.”
4. Adoption Process
The four main steps of the adoption process are:
(i) Approval at a WNT meeting
(ii) Endorsement by the Joint Meeting by written procedure
(iii) Endorsement by the Environment Policy Committee by written procedure
(iv) Adoption by the Council by written procedure
4.1 How long is the adoption process from WNT approval to Test Guidelines publication? Is it possible to shorten the approval process?
It takes now approximately 5 month to publish Test Guidelines that have been approved by the WNT. This time has been shortened as much as possible and it is not the bottleneck compared to the time needed for the validation and for commenting the draft Test Guidelines. It should be noted that it is possible to use the written procedure for WNT approval (Guidance Document N°1, Par. 22). Usually, after WNT approval, comments are only of an editorial nature.