Process & standards

The standards applied for prequalification assessment include the quality management standards ISO 13485:2003: Medical devices — Quality management systems and ISO 13485:2016: Requirements for regulatory purposes, and relevant international standards and guidelines produced by the former Global Harmonization Task Force and the International Medical Device Regulators Forum. As a general rule, the criteria for inspection of manufacturing site(s) are product-specific. And since WHO inspection focuses on the suitability of the implemented processes and procedures for the reliable supply of IVDs to WHO Member States, customer-related issues that may be covered only in general terms in ISO 13485 are inspected in detail. Importantly, the inspection will also verify the content of the product dossier (or, in the case of an abridged prequalification assessment, the technical documentation) through review of reports and raw data onsite, and interviews with the personnel involved. 

Actual inspection of manufacturing site(s) is based on the principles outlined in ISO 19011:2018 Guidelines for auditing management systems. Additional references relating to good practice for the manufacture of IVDs, including other ISO standards, are used during prequalification assessment.

Initial inspection as part of full prequalification assessment

Under full prequalification assessment, the initial inspection of the manufacturing site will be performed in two stages:

• Stage 1 inspection, usually a desk audit, but sometimes an on-site inspection, will evaluate the documentation related to the quality management system (QMS) to ensure readiness for the stage 2 inspection. General information about the documented QMS (including the quality manual and manufacturing processes, organigram, workflows, critical suppliers and floor plan) will be reviewed during the stage 1 inspection to establish the readiness of the manufacturer's QMSand to prepare for an on-site visit. Any issues of concern will be communicated to the manufacturer. A satisfactory stage 1 inspection is a precondition for a stage 2 inspection.
• Stage 2 inspection will comprehensively evaluate the effective implementation of the QMS and production processes through an onsite(s) inspection. The inspection team is composed of WHO staff, external experts (inspectors) appointed by WHO as well as, potentially, interpretors and observers. 

As part of the preparation for an on-site inspection for prequalification, a dossier review summary report is prepared by WHO dossier assessors and submitted to the lead inspector. When the lead inspector is satisfied that the summary dossier review report is complete, the report is shared with the quality and technical inspectors. Other documentation reviewed may include previous inspection reports. Issues arising from these reports are noted. Any other relevant documentation or information is made available to all of the participating inspectors for review.

Inspection report following on-site inspection

A preliminary non-conformance report detailing issues of concern (if any) will be provided to the manufacturer on the final day of the inspection. A final inspection report, including the graded nonconformities will be issued to the manufacturer after the inspection of the manufacturing site(s). All nonconformities must be corrected by the manufacturer through suitable corrective actions addressing the root cause of each nonconformity. The manufacturer will have the opportunity to submit no more than two corrective action plans. Depending on the nature and number of nonconformities, objective evidence of effective implementation of the proposed corrective actions may be required. WHO will assess the information provided and decide whether the corrective action plan is acceptable. Conformity with prequalification requirements will be established based on assessment of such information. In some instances, the number and criticality of nonconformities may require that effective implementation of proposed corrective actions must be verified in a follow-up inspection, before the nonconformities can be closed off.

If the product is prequalified, a summary of the findings of the inspection of the manufacturing site(s) will be included in the WHO prequalification public report. In certain cases, WHO may agree, at its sole discretion, to permit the manufacturer to correct specific nonconformities after prequalification, provided that the manufacturer commits in writing to address them by an agreed-upon deadline. Such a "commitment to prequalification" will be reflected in the WHO prequalification public report and confirmed during the re-inspection. Failure to comply with prequalification commitments within agreed deadlines will result in delisting of the product from the WHO List of Prequalified IVDs. If the manufacturer does not meet WHO prequalification requirements, or if any of the other required conditions are not met, the prequalification application will be cancelled.

Waiver of manufacturing site inspection

An inspection of a manufacturing site(s) may be waived by WHO in writing under defined circumstances such as a recent inspection of appropriate scope by a WHO-recognized national regulatory authority or by a Medical Devices Single Audit Program (MDSAP) participating Auditing Organisation. The full report and other requested documentation must be made available to WHO inspection staff members for review. This documentation shall contain sufficient detail on the processes and records related to the type of products in prequalification. WHO will take into account any objective evidence contained within an MDSAP audit report that demonstrates compliance with medical device prequalification requirements.