The 10-valent pneumococcal conjugate vaccine produced by GSK is of suitable quality and efficacy for procurement by United Nations agencies and has considerable potential to reduce mortality and morbidity from pneumococcal infection. The World Health Organization (WHO) therefore prequalified the one-dose presentation of Synflorix™ (on 12 October 2009) and the two-dose presentation (on 19 March 2010). United Nations procuring agencies and the manufacturer were notified accordingly.
Synflorix™ is a preservative-free vaccine. As a two-dose presentation of a preservative-free liquid vaccine has not previously been used in United Nations supported programmes, its use requires specific training for immunization staff and will undergo formal post-introduction monitoring.
Current immunization policy and practice for liquid vaccines allows health workers to retain at the end of an immunization session opened multidose vaccine vials which have unused doses of vaccine still in the vial. The opened vial can be stored at 2-8°C for up to 28 days and used in subsequent immunization sessions. This is because, to date, the liquid vaccines used in UN supported EPI programmes have contained a suitable preservative.
Synflorix, however, does not contain a preservative and thus a partially used vial, if contaminated via mishandling, may support growth of bacterial or fungal contaminants during extended storage. (The same situation could occur if preservative-free lyophilized multidose vaccines were mishandled and kept during extended storage.)
WHO considers that the risks can be mitigated through re-training of programmatic staff and the benefit-risk ratio remains favourable to use of this presentation of the vaccine.
To facilitate safe use of the two-dose presentation of Synflorix™:
- Labelling will clearly indicate the need for opened vials (*) of the product to be discarded after six hours or at the end of the immunization session, whichever is earlier (The six hour limit is in line with the current practice for preservative-free lyophilized multidose vaccines used in UN supported immunization programmes).
- There will be additional material supplied with vaccine deliveries describing appropriate practices for safe use of the presentation.
- There will be a training programme coordinated by WHO, for health workers in country EPI programmes.
- There will be monitoring, coordinated by WHO, of immunization clinic practices in country EPI programmes regarding use of this presentation.
In addition, as noted in the WHO letter approving the two-dose presentation for supply through United Nations agencies, additional post- introduction monitoring will be conducted to monitor Adverse Events Following Immunization (AEFIs) associated with potential mishandling of the product. As the two dose vaccine is the only Synflorix presentation available through the AMC, the study is to be conducted in a GAVI-eligible country which receives the vaccine through the AMC mechanism, and where there is an infrastructure for monitoring AEFIs in the country. The study protocol describing this monitoring was proposed by the manufacturer, has been reviewed by WHO and agreed to by the national authorities.
AEFIs could occur in any immunization programme, but the crucial issue is whether any AEFIs detected are causally linked to the use of a vaccine. In general, following the introduction of a new vaccine into the immunization program there is greater attention to AEFIs and in countries with a high underlying infant mortality, coincidental serious AEFIs will be reported. Therefore, the proposed phase IV study is seen as an important measure of the effectiveness of immunization staff training on correct use of vaccine in a two-dose liquid preservative-free presentation.
The study of the safety of use of the two-dose presentation of Synflorix is proposed for two years. Routine reporting to WHO will be at six-month intervals following commencement of the study. The prequalification status will be reviewed after evaluation of the 12-month report, which is expected to be made available to WHO in the second half of 2011 before wider introduction is anticipated.
Organizations considering direct procurement of Synflorix in the two dose presentation should take into consideration the issues relating to this novel presentation and consider whether training in and monitoring of the correct use of the presentation can be implemented in their proposed programme.