WHO vaccine prequalification works to ensure the continued acceptability and reliability of vaccines used in national immunization programmes. Support for the monitoring and resolution of complaints and reports of adverse events following immunization (AEFIs) is a key element of this process, carried out in collaboration with vaccine stakeholders — in particular, national regulation authority(ies) (NRA(s)) — and relevant teams within WHO working on vaccines safety, or issues relating to substandard and falsified health products.

Product complaints can be submitted to WHO by completing a product complaint form.

WHO follows up on complaints received about prequalified products. Complaints investigated include those relating to vaccine quality. Additionally, national control laboratories (NCLs) may forward a complaint to WHO when testing results for a prequalified product are unsatisfactory. In such cases the NCL must provide not only the testing results but also validation reports, standard operating procedures and control charts for WHO to review and determine whether arbitration testing should be commissioned.

WHO investigation of a complaint

A WHO investigation may include:

• review of the batch records maintained by the manufacturer and the NRA responsible for regulatory oversight of the vaccine, to detect any potential deviation during the manufacturing process that could impact on the quality of the vaccine
• review of results of the continuous targeted testing programme performed by the NRA and NCL
• additional testing of a vaccine lot (but only if the clinical and/or epidemiological information about the AEFI case(s) indicates a potential vaccine quality problem and after completion of review of the relevant manufacturing and control documentation)
• manufacturing site inspection.

Satisfactory management by the manufacturer of quality complaints and AEFIs is a core requirement for maintaining prequalified status.

AEFI follow-up

For an AEFI, detailed field investigation — based on the programme’s operational structure and the expertise available — can be undertaken. Basic preliminary investigation by local immunization programme managers may be sufficient if the cause of the reported AEFI is very clear.

In the case of serious AEFIs, WHO will conduct an investigation according to established procedures. A detailed AEFI investigation to assess causality may need to be carried out by WHO if the AEFI:

• is serious, part of a cluster or a suspected signal of new causal association
• it is a suspected immunization error
• appears on the list of events defined for AEFI
• it causes significant parental or public concern.

Complaint investigation follow up

Following conclusion of a complaint investigation, WHO may recommend one or both of the following:

• that the manufacturer’s vaccine lots should be monitored more closely, through additional testing, visits to the manufacturing facilities accompanies by representatives of the NRA responsible for the regulatory oversight of the product, and/or review by WHO of the corrective/preventive actions during a probationary period
• that purchase of the vaccine by United Nations agencies be suspended pending resolution of the problem
• that due to failures relating to gaps in the manufacture and/or quality system of the manufacturer, a complete reassessment of the vaccine be undertaken.