Site inspections are required for those manufacturers applying for the prequalification of new products to be evaluated for purchase by United Nations agencies. They are necessary:

• as part of the initial evaluation,
• as follow-up to corrective actions taken by the manufacturer following WHO recommendations, and
• for reassessment purposes 

They may also be deemed necessary as a result of complaints or reports of serious adverse events following immunization (AEFIs) if a quality problem is suspected.

The objectives of a site audits are to assess whether:

• a vaccine complies with WHO recommendations for production and quality control
• a vaccine meets UN specifications for tender (which reflect the needs of the immunization programmes at country level)
• the manufacturer of the vaccine has an adequate quality system in place
• a vaccine is produced in compliance with WHO-recommended good manufacturing practice.

The site inspection also covers:

• labelling, packaging
• post-marketing surveillance
• vaccine vial monitor implementation (when required)
• stability programme implementation.

In line with the WHO vaccine prequalification procedure, as far as possible site audits will build on information gathered through inspections performed by national regulatory authorities REST OF THIS SENTENCE MAY NEED MODIFYING that meet the critical indicators established by WHO for vaccine prequalification purposes. In such cases, if detailed reports of inspections are made available for WHO review, WHO may decide, in agreement with the manufacturer, to organize an abbreviated site audit.

Inspection process

The site inspection will take place as soon as possible – generally within two months – after satisfactory test results for the vaccine samples lot testing phase have been received. 

A bilateral consultation meeting will be held between WHO and the relevant NRA, either at the beginning or at the end of the inspection to discuss regulatory matters related to the vaccine in question and to lay the basis for the letters of agreement BETWEEN????? it and WHO NEEDS FURTHER EXPLANATION AND POSSIBLE LINK TO A SAMPLE. (WHO will establish letters of agreement with all the NRAs responsible for the oversight of prequalified products.)

Topics to be covered during the meeting will include:

• commitment for testing and release of vaccine lots for UN agencies
• the need for feedback on findings during inspections
• updates on safety and efficacy data, variations to the marketing authorization/licence that may have been requested
• marketing authorization/licence renewals
• recalls or withdrawal of lots.

DOES THIS STILL APPLY? WHO site inspections of manufacturing facilities, or results of consultations held with the NRA, may trigger a follow-up assessment of the NRA for one or more functions. In such cases, the follow-up assessments should be performed within six months. The outcome of the follow-up assessment may have an impact on the final decision about the prequalification of the vaccine in question. The findings and recommendations will be discussed with the company on a daily basis, as required during the site inspection. The manufacturer may be requested to prepare a corrective action plan to address critical recommendations and establish deadlines for receiving responses. LAST TWO SENTENCES ARE CONFUSING. LINKED TO THE FOLLOW-UP REASSESSMENT OF THE NRA OR THE SITE INSPECTION?

Site inspection report and outcome

A draft report that includes the main findings, recommendations and closing remarks is prepared by the WHO inspection team and shared with the manufacturer. The findings and recommendations will also have been reported to manufacturer and NRA representatives during the closing meeting, thus providing an opportunity for discussion, questions and clarifications.

The final report with findings, recommendations and conclusions is sent to the manufacturer, with a copy to the NRA, within 30 days of completion of the visit VISIT TO NRA MENTIONED ABOVE? BUT ABOVE THE VISIT IS MENTIONED AS TAKING PLACE BEFORE OF AFTER, MEANING THAT PREVIOUS SENTENCE HERE IS UNCLEAR. If the manufacturer does not comply with the agreed WITH WHOM? deadlines, the prequalification process may be terminated.

The final decision on the acceptability of the product for supply to UN agencies may be taken in consultation with an ad hoc committee on vaccine prequalification convened by WHO for this purpose.

Once WHO considers that the evaluation is complete, provided the outcome is satisfactory, it will send a letter to the UN agencies and to Gavi (in the case of Advance Market Commitment-eligible products), advising on:

• the compliance of the vaccine with both the WHO requirements and the specifications of the relevant UN agency
• the role of the NRA in certifying this.

A copy of this letter is addressed to the manufacturer, the NRA/national control laboratory responsible for lot release, the relevant WHO regional and country offices and the WHICH DEPT NOW? management of WHO’s Department of Immunization, Vaccines and Biologicals.

The vaccine will be included in the WHO list of Prequalified Vaccines immediately after the letter is sent to the UN agencies. A page providing the basis for the acceptance of the prequalification of the specific vaccine will also be included in the list. 

The prequalified status of a vaccine is valid until a new reassessment is scheduled by WHO.

DO WE NEED SOMETHING ABOUT SHORTER SITE INSPECTION FOR STREAMLINED PROCEDURE?