Invitation to submit a product dossier & screening

If, following submission of a completed pre-submission form, WHO has determined that the product in question should under go full assessment, it will formally invite the manufacturer to submit a product dossier.

Upon receipt of a product dossier, WHO will screen it for completeness. This screening is aimed at ensuring that all requisite sections of the product dossier have been submitted and as such does not take into consideration the technical appropriateness of the information provided in the product dossier.

If the product dossier is incomplete, the manufacturer will be requested to provide supplemental information to complete the product dossier within a specified deadline. The manufacturer will be given two opportunities to submit the required supplemental information within the deadlines set by WHO. In the event of non-compliance, the product dossier will be rejected on grounds of incompleteness and the application will be cancelled.

Product dossiers that are considered complete will be retained by WHO for product dossier review.

WHO will inform the manufacturer in writing on the outcome of the dossier screening.

Product dossier

Many terms are used internationally to describe a product dossier. They include: standard technical documentation; technical file; summary technical documentation; product summary file; and product master file. For the purpose of IVD prequalification, WHO uses the term "product dossier".

WHO expects that a manufacturer submitting an IVD for prequalification prepares and either holds, or can provide timely access to technical documentation that shows how the IVD was developed, designed and validated, and is manufactured. This technical documentation — controlled in the manufacturer's quality management system (QMS) — is likely to be extensive and may be revised over time to reflect any changes made during the life cycle of the product.

A manufacturer submitting an IVD to WHO for evaluation for prequalification must compile a product dossier from its existing technical documentation to provide evidence that the product conforms to the internationally recognized set of safety and performance principles described in the International Medical Device Regulators Forum document Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices.

Components of full assessment

Full assessment of an in vitro diagnostic (IVD) for prequalification has three components:

• review of a product dossier
• laboratory evaluation of performance and operational characteristics
• manufacturing site inspection
• labelling review.

Dossier review

WHO reviews the product dossier to:

• assess the product and how it performs
• assess manufacture of the product
• determine whether the manufacturer's quality management system is of an adequate standard to warrant a site inspection.

Information that was previously submitted in the pre-submission form will also be considered by WHO during the review of the product dossier.

Performance evaluation

Independent verification of its performance and operational characteristics is essential for any IVD submitted for prequalification. It also allows WHO to verify performance and operational characteristics that are considered essential for use in resource-limited settings. The data obtained complement the verification and validation data submitted by the manufacturer in the product dossier. Manufacturers can choose between performance evaluation organized by WHO and carried out by a specified WHO Collaborating Centre, or a designated laboratory. In the latter case, the manufacturer must both organize the evaluation and cover its cost.

Manufacturing site inspection

An initial inspection is performed in two stages. Stage 1 usually takes the form of a desk audit to establish the readiness of the QMS for inspection and to prepare for an on-site visit. A satisfactory audit is a pre-condition for proceeding to the Stage 2 inspection. Stage 2 consists of an on-site inspection to evaluate the implementation of the QMS and of production processes. 

Labelling review

Product labelling is reviewed as part of the pre-submission form, product dossier, performance evaluation and inspection of manufacturing site(s).