Post-prequalification Procedures and Fees: Prequalified IVDs
In vitro diagnostics (IVDs) submitted for prequalification assessment and that meet WHO prequalification requirements are included in the WHO List of prequalified IVDs. In order to maintain the prequalification status of a product the manufacturer must, within any applicable deadlines:
- fulfil prequalification commitments
- report changes relating to the product
- submit an annual report for the product
- meet post-market surveillance obligations
- open the manufacturing site(s) for re-inspection
- ensure the ongoing compliance of the product with WHO prequalification technical specifications.
Fulfilment of prequalification commitments
Commitments to prequalification must be fulfilled by the manufacturer within the agreed deadlines in order to keep the prequalification status of the product. Failure to meet prequalification commitments within the agreed deadlines will lead to delisting of the product(s) from the WHO List of Prequalified IVDs.
For any planned change to a prequalified product or the process by which it is manufactured, the manufacturer must determine its significance with respect to the function, performance, usability, safety and applicable WHO requirements for the prequalified IVD and its intended use. All substantial changes are considered as reportable changes. A reportable change is one that is demonstrated, through risk analysis, to have a potential impact on the function, performance, usability, or safety of a prequalified IVD. In addition, some administrative changes must also be reported. Reporting to WHO of reportable changes is mandatory for all prequalified IVDs. To meet WHO prequalification requirements, a manufacturer must have an established, maintained and implemented procedure for categorizing and documenting any changes to the product and/or the quality management system under which the product is manufactured.
The manufacturer of a prequalified in vitro diagnostic (IVD) must submit to WHO an annual report for that product ‒ in a summarized form and in the format prescribed by WHO. The report must give sales details and information about any (all) categories of complaints received.
Regulatory oversight of IVDs is weak in many countries ‒ for both pre-market assessment and post-market activities ‒ and widely acknowledged as a shortcoming with respect to ensuring the safety, quality and performance of IVDs. Moreover, the type of IVDs that are most appropriate and well adapted for use in resource-limited settings are not likely to have undergone any stringent pre-market and post-market regulatory oversight. Therefore both pre-market assessment and post-market surveillance are recommended.
Pre-market surveillance of an IVD generates information on its safety, quality and performance, while post-market surveillance of an IVD consists of both and proactive measures: post-shipment/pre-distribution lot testing and complaint reporting. Post-prequalification also includes mandatory manufacturer notification of changes to the product or the quality management system. Post-market information on IVDs empowers national regulatory authorities and WHO to detect, investigate, communicate and contain events that threaten public health security and to take appropriate action. As soon as an IVD is accepted into the prequalification assessment process, and as long as that IVD is included in WHO’s list of prequalified IVDs, the manufacturer must, as a condition of prequalification, follow WHO guidance for post-market surveillance of IVDs.
Routine re-inspection is carried out to ensure continued compliance with prequalification requirements. Routine re-inspections typically take place every three and up to five years after prequalification of a product, unless an earlier re-inspection is deemed necessary by WHO.
Ongoing compliance with technical specifications
The purpose of the WHO Prequalification Technical Specifications Series is to provide technical guidance to manufacturers of IVDs seeking WHO prequalification. Manufacturers must comply with the requirements laid down in the relevant publication in this series. For products prequalified before the relevant publication is issued, a transition period will apply.
Manufacturers must comply with the relevant technical specifications as outlined in the aforementioned series within three years from their publication. Compliance will be verified during the re-inspection. Failure to do so will result in the delisting of the product from the WHO List of Prequalified IVDs.
An annual fee of US$ 4000 is levied for each product listed on the WHO List of Prequalified In Vitro Diagnostics. An invoice for the annual fee will be issued by WHO to the manufacturer on or before 1 October of each year. The annual fee is applicable to all IVDs that, by 1 September of that year, have been listed for 12 months or more. Payment of the annual fee must be made before 30 November of the calendar year in which the invoice is issued.
Reporting and communication of outcomes after delisting or suspension of a product
If a prequalified product is suspended or delisted, at any time and for any reason, such suspension or delisting will not prejudice or otherwise affect WHO’s rights to use, publish, issue, share with with relevant authorities of WHO Member States as well as with UN agencies and other relevant intergovernmental organizations, and/or make publicly available (in each case, in accordance with relevant provisions of this document, including provisions regarding the protection of any commercially-sensitive information of the manufacturer) any outcomes, reports, notices and/or results – whether in draft or final form, and whether positive or negative – arising from or relating to the prequalification assessment process, including without limitation any WHO Notices of Concern, WHO Notices of Suspension, WHO information notices for users and/or manufacturer-issued field safety notices.