Office International des Épizooties World Organisation for Animal Health created in 1924 in Paris

2 OIE Procedure for Validation and Certification of Diagnostic Tests By François Diaz Responsible for the OIE procedure for Diagnostic Tests assessment Scientific and Technical Department

3 Introduction Purpose of the procedure (2 slides) Outline of the procedure (1 slide) Elements to be provided by the applicant (6 slides) Procedure (9 slides) Website (1 slide)

4 Purpose of the procedure (1/2) Developed to meet the needs of Member Countries, the aim of this procedure is : 1. to validate and certify the ‘fitness for purpose’ of a diagnostic test. 2. to produce an OIE register of recognised diagnostic kits (available on the OIE web site). All diagnostic tests for diseases, including zoonosis, caused by pathogens (viruses, bacteria, prions and parasites) present in terrestrial and aquatic animals can be validated and certified by the OIE procedure.

5 Purpose of the procedure (2/2) The concept of ‘fitness for purpose’ 1. Demonstrate population ‘freedom’ from infection (prevalence apparently zero) a) ‘free’ with and/or without vaccination, b) historical ‘freedom’, c) re-establishment of ‘freedom’ following outbreaks; 2. Demonstrate freedom from infection or agent in individual animals or products for trade purposes; 3. Demonstrate efficiency of eradication policies; 4. Confirmatory diagnosis of clinical cases; 5. Estimate prevalence of infection to facilitate risk analysis (surveys, classification of herd health status, implementation of disease control measures); 6. Determine immune status in individual animals or populations (post- vaccination).

6 Outline of the procedure Validation Assessment Notification Decision Meeting of the BSC InternationalCommittee Final decision Dossier + Fees Applicant Contact

7 Elements to be provided by the applicant The completed application form The applicable fee The applicant shall send the above mentioned elements to the OIE Director General

8 The application form (1/3) There are two main parts in this application: 1. General Information 2. Validation Information

9 The application form (2/3) General Information: 1. Information about the applicant, 2. Purpose of the test, 3. Test Details, 4. Technical Information about the test kit.

10 The application form (3/3) Validation Information: 1. There are 4 stages of validation 2. The 4 stages shall be achieved in order to validate and certify a diagnostic test Stage 1: Calibration, Repeatability data, Analytical specificity data and Analytical sensitivity data. Stage 2: Negative reference animals/samples, Positive reference animals, Experimental animals, Threshold determination, Performance estimates, Diagnostic sensitivity and specificity estimates – with defined reference animals, Diagnostic sensitivity and specificity estimates – without defined reference animals and Agreement between tests. Stage 3: Laboratory identification, Evaluation panel and Reproducibility. Stage 4: Laboratories, Test applications, International reference standards, Inter- laboratory testing programmes and International recognition.

11 The applicable fee (1/2) The assessment fee: €. The applicant shall pay this first part of the basic fee when he sends his dossier in order to start the procedure The annual fee: 0.1% of pre tax annual cumulated turnover of the previous year gained from sale of the diagnostic test validated and certified by OIE. The applicant shall pay this second part of the basic fee, if the diagnostic test is validated and certified, in order to maintain it on the OIE register. The renewal fee: €. Every 5 years, the manufacturer shall resubmit a dossier and pay for a new assessment.

12 The applicable fee (2/2) Conditions of reimbursement When the applicant sends his dossier, if it is immediately clear to the OIE Secretariat for Validation, Certification and Registry of Diagnostic Assays (OIESVCRDA) that the test for which an intention to submit an application has been received does not fall within the OIE priorities and scope. The fee paid by the applicant will be sent back to the applicant. During the administrative assessment by the OIESVCRDA, if the application cannot be assessed (e.g. failure to provide sufficient data, information or clarification requested), the fee paid will be reimbursed to the applicant with a reduction to cover administrative costs (15%).

13 Procedure 1. Before submission 2. Submission of the application to the Director General of the OIE 3. Validation of the application by the OIESVCRDA 4. Scientific Evaluation 5. Biological Standards Commission’s opinion 6. Unfavorable opinion: an appeal procedure is possible 7. Favorable opinion: end of the procedure 8. OIE Logo

14 cc Before Submission (1/8) Before submission, the applicant should fill in the Application Form (which can be downloaded on the OIE web site). The OIE Central Bureau, through the OIESVCRDA, will be able to provide more procedural guidance during this pre- submission phase and to prepare the assessment process. The conditions, including the date of submission, should be defined in accordance with the OIESVCRDA in order to optimize the timing of the procedure.

15 Submission of the application form to the Director General of the OIE (2/8) The applicant should submit the completed application form and the relevant fee at the same time. For the application form, one copy in a CD-Rom (Word) and one copy in paper format. If possible, the applicant should provide with his application a ‘mock-up’ or specimen of the presentation of the diagnostic test ‘ready-to-use’. If the diagnostic test is validated, mock-ups in English, French and Spanish and in color should be sent to the OIE in all cases before the test is placed on the market.

16 Validation of the application form by the OIESVCRA (3/8) The OIESVCRDA will send the applicant an acknowledgement of receipt of the dossier and will ensure that the application is valid, within 30 days following receipt of the dossier. In the event that the OIESVCRDA requires additional data (the clock is stopped), the dossier could only be accepted after receipt and verification of the information submitted. In case of a positive outcome, the OIESVCRDA will notify the applicant in writing that the dossier is acceptable. The names of the chairperson and the reviewers, the index number for the identification of the application and the timetable for evaluation will be attached to the letter confirming the acceptance of the dossier.

17 Scientific Evaluation (4/8) Start of the procedure, as soon as each reviewer has receives the full dossier and OIESVCRDA the AR. Day 1 Start of the procedure Day 30 Reviewer to provide a first report to the CRP Day 45 Draft assessment report from the CRP and potential questions sent to the OIESVCRDA (who sends the questions to applicant). If question: stop clock Day 46 Restart clock Day 60 Final assessment report sent to the OIESVCRDA and then from the OIESVCRDA to Members of the BSC Day 80 Comments from the BSC

18 BSC’s opinion (5/8) The OIE will ensure that the opinion of the BSC is given within 120 days. Day 120 BSC discussion, adoption of BSC’s opinion, BSC’s assessment report. Favorable Opinion: It is the end of the procedure. Unfavorable Opinion: An appeal procedure may be initiated by the applicant. In this case the clock is stopped.

19 Unfavorable Opinion: an appeal procedure is possible (6/8) The applicant may notify the OIESVCRDA his intention to appeal within 10 days of receipt of the opinion. The grounds for appeal must be forwarded to the OIE within 30 days of receipt of the opinion. If the applicant wishes to appear before the Biological Standards Commission, the request should also be sent at this stage. This new assessment of the dossier will be carried out by one new reviewer. The appeal procedure duration is 60 days.

20 Favorable opinion: end of the procedure (7/8) Day 130 Transmission to the OIE General Director Day 135 Decision of the Central Bureau that the diagnostic kit is proposed for inclusion in the register. Notification to the applicant/ OIE approved number Next International Committee meeting of OIE: confirmation of inclusion in the register and update of the register within 7 days after the vote of the International Committee. The producer is authorized to use the OIE logo on any relevant document or equipment associated with the test.

21 OIE Logo (8/8) Fitness for purpose validated and certified by OIE Register number: The OIE validated and certified logo shall consist of the initials OIE taking the following form If the logo is reduced or enlarged the proportions must be respected.

22 OIE Web site and information about the procedure Let’s go directly to the OIE web site !!!

23 World organisation for animal health 12 rue de prony paris, france Tel: 33 (0) – Fax: 33 (0)