Invitation to Manufacturers of diagnostic products for diagnosis of dengue, to Submit an Expression of Interest for Product Evaluation by the WHO Expert Review Panel for Diagnostic Products

Reference of the ERPD Round: 24-NTD-0003 

Concerning Diagnostic Tests for: Dengue infections

A. Background

WHO supports the procurement of diagnostic products and related laboratory items for the diagnosis and management of many communicable and non-communicable diseases. The landscape of in-vitro diagnostics (IVDs) has blind spots particularly for emerging diseases and zoonoses with epidemic and pandemic potential and in the field of Neglected Tropical Diseases (NTD) diagnostics . In other areas IVDs are rapidly evolving. Both situations pose significant challenges to procurers, health-care programmes, and authorities for public health and patient care. these challenges are compounded by revisions to regulatory frameworks that can disrupt the availability of some diagnostics.

While the WHO IVD prequalification programme (WHO PQ) informs procurement of quality-assured, safe and performant IVDs for the benefit of public health, currently, many WHE and NTD diagnostics do not fall within the scope of WHO Prequalification or of WHO Emergency Use Listing process. Given the intersection of emerging diseases and zoonoses¹ and neglected tropical diseases diagnostics needs in the context of the Grade 3 dengue health emergency, the Emerging Diseases and Zoonoses unit (EPP/EZD) and Public Health laboratories (CSR/PHL) units within the WHO Health Emergencies Programme (WHE) are jointly working with the Neglected Tropical Diseases (NTD) department and WHO PQ to organize an ERPD round of assessment of the risks and benefits associated with non-WHO prequalified IVDs, including dengue multi-analyte rapid diagnostic tests, molecular and serological assays.

B. The Expert Review Panel for Diagnostic products (ERPD)

The Expert Review Panel for Diagnostics (ERPD) is an independent advisory body of technical experts, coordinated by WHO PQ. The role of the ERPD is to assess the risks and benefits associated with procurement of IVDs that may have a high public health impact but are not yet prequalified or that are not currently eligible for Prequalification. The risks of procurement and use of the products are considered in a specific binding context to determine their quality assurance risk category. The assessment is based on a desk review of available evidence of compliance to transparent criteria and will provide advice for decisions regarding time-limited procurement in specific conditions. ERPD Members are technical experts in the field of IVD performance, quality and safety and/or with extensive scientific knowledge and experience of diagnostic procedures in the relevant settings and disease area. The complete process involves WHO NTD and WHE (PHL and EZD) publishing an "Invitation to Manufacturers (ItM) to Submit an Expression of Interest (EOI) for Product Evaluation." Subsequently, manufacturers will be requested to fill a diagnostic product questionnaire to WHO NTD and WHE, which will be submitted to the WHO PQ team who will coordinate the ERPD review. The results of the review are then communicated to the manufacturers by the WHO NTD, EZD and PHL units.

C. Scope of the present Invitation to Manufacturers 

The purpose of this ItM is to invite manufacturers to submit an EOI for the product evaluation of urgently needed In-Vitro Diagnostics (IVDs) by the WHO ERPD panel. The invitation specifically pertains to several types of dengue IVDs. Additionally, the document provides the required specifications or quality assurance criteria for these IVDs.

Manufacturers whose IVDs are intended for diagnosis of acute dengue infection and who meet all of the required specifications and quality assurance criteria defined below are encouraged to apply by completing a product submission form (questionnaire) and necessary supporting documentation to ERPD-NTD@who.int.

WHO PQ team will coordinate the ERPD review process and provide recommendations for procurement decisions and facilitate the supply of IVDs by WHO NTD, and WHE OSL.

D. Eligibility criteria

To be eligible for ERPD review, manufacturers must meet the following criteria: 

Quality assurance criteria

1. Quality management system: The manufacturer should provide evidence that the considered products are designed and manufactured under a relevant quality management system, compliant with applicable ISO 13485 or equivalent standard (see Section E.2 below).
2. The legal manufacturer should be original equipment manufacturers (OEM)
3. The company must also have the necessary registrations to enable sale and export out of the home country. Chinese companies must have NMPA for export.
4. Operational capabilities: The manufacturer should provide evidence of their ability to support design, manufacturing, distribution, sales and post-market activities such as customer support, response to regulatory vigilance activities, in and for all WHO Member States involved in the management of dengue. 
5. The application is limited to manufacturers who commit to submit their product to PQ (when eligible), SRA approval or registration in accordance with the product classification.
   

Technical criteria

To be eligible for ERPD review, the products must meet the following criteria: 

1. Antigen and antibody rapid diagnostic tests (RDTs): The IVD must be a rapid test (≤30 mins) for diagnosis of acute dengue infection. The design of the test must include the detection of antigen (NS1) and antibodies (IgM) (+/- IgG) of all serotypes, though they need not differentiate the serotypes. The devices must be intended for point-of-care testing.
2. NAAT tests: The IVD must be a nucleic acid amplification assays for diagnosis of acute dengue infection. The test must be dengue specific² and could be pan specific and/or serotype specific (multiplex). The device must intend for point-of-care testing, near-patient testing or laboratory-based testing.
3. Enzyme immunoassay tests: The IVD must be an immunoassay e.g., ELISA. The design of the test must include detection of antigen (NS1) or antibody (IgM) of all serotypes, though they need not differentiate the serotypes. The device must allow concurrent testing of multiple samples and must be intended for laboratory-based testing.

All manufacturers interested in submitting applications for review by the ERPD are kindly requested to submit the following information:

1. A cover letter expressing interest (Expression of Interest or EoI) in submitting the product(s) to the ERPD for review. The cover letter should also indicate the authorized contact for the manufacturer.

2. One of the following documents, substantiated by the most recent inspection reports: 

• An ISO 13485 certificate; covering the product manufacturing activities or
• A certificate ensuring that the IVD (device, reagents, and associated equipment) is manufactured at a site that is compliant with ISO 13485 requirements: or 
• an equivalent quality management system recognized by a stringent regulatory authority of the Founding Members of the Global Harmonization Task Force (GHTF); or 
• a letter from WHO ensuring that the manufacturing site has undergone inspection by the WHO Prequalification of In-Vitro Diagnostics Program and has been found compliant with WHO prequalification requirements. 
• or single audit programme for medical devices (MDSAP)
  

3. The  ERPD questionnaire, including all relevant attachments and evidence supporting product claims (refer to Annex 1)

The application must encompass all attachments that are accessible at the time of submission and that have been specified in the questionnaire. Additional information regarding any planned studies or documentation and the timelines can also be provided. It is imperative that all available evidence and the requested documents and information are comprehensively enclosed. If any of these items are missing or incomplete, a justification for their absence should be provided.

Incomplete Expressions of Interest, as well as those submitted after the Closing Date, will typically be disregarded unless WHO, at its discretion, decides otherwise.

F. Confidentiality

All information provided by manufacturers will be received by WHO NTD-WHE and shared with the WHO ERPD coordinator for the purpose of facilitating their review of the submission and provision of advice to WHO NTD-WHE. All parties involved will operate under a confidentiality agreement with WHO PQ as the coordinating entity . The outcomes of the ERPD review, as well as the advice provided in the review report, in connection with the manufacturers’ Expression of Interest, will be shared with and used by WHO NTD-WHE and the relevant partners as the basis for procurement decisions.

G. Instruction for submission

Submission should be submitted by electronic means (either via email or web-based download service) to ERPD-NTD@who.int by the specified deadline (7 July 2024).

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¹ Coronaviruses (SARS-CoV-2, MERS-CoV), mpox, arboviruses, plague
² Multiplex tests for dengue, Zika, chikungunya will be considered in future EOIs but as this EOI focuses on tests to respond to dengue-specific epidemics, only dengue-specific tests will be considered.
³ Common thermocyclers in LMICs include: ABI 7500/7500 FAST/7500 FAST Dx, ABI 7300; Qiagen Rotor-GeneQ, Bio-Rad CFX96, Roche LightCycler and QuantStudio5
⁴ Dengue status confirmed by paired samples with early samples tested for dengue or other flaviviruses using NAAT or NS1 and subsequent samples for respective IgM.