Immunization standards

Update on two-dose presentation of preservative-free 10-valent pneumococcal conjugate vaccine from GlaxoSmithKline (GSK) (Synflorix™).

14 May 2012

The World Health Organization (WHO) prequalified the two-dose presentation of Synflorix™ on 19 March 2010. Synflorix™ is a preservative-free vaccine. The approval indicated that as a two-dose presentation of a preservative-free liquid vaccine has not previously been used in United Nations supported immunization programmes, formal post-introduction monitoring would be initiated and the prequalification status would be reviewed after receipt of interim and final reports.

Interim data (described below) have been received and reviewed. Taking into account that risk-benefit estimates of using this presentation in high disease burden countries show that the benefits outweigh the potential risks associated with the presentation, the two-dose presentation of Synflorix™ remains prequalified.

The presentation is considered suitable for supply through the UN to further countries. Each country considering introduction of this vaccine presentation will need to ensure its programmatic readiness to do so, as described below.

Interim data from ongoing post introduction studies that have been reported to and reviewed by WHO are:
From Kenya: Programmatic surveys (at 2, 6 and 11 months post introduction); 12-month interim results from a phase IV safety study (examining for Adverse Events Following Immunizations (AEFIs) potentially associated with improper handling of the vaccine presentation),
From Ethiopia (which introduced the vaccine later than Kenya): a programmatic survey at 2 months post introduction.

WHO expert reviewers commented that the studies were of a high quality.

The safety study data did not indicate any increase in AEFIs associated with the use of two-dose preservative free PCV10 compared to the control arm receiving a ten-dose preserved pentavalent vaccine.

The programmatic survey results indicated that special attention to training of health care staff is needed for the proper use of the Synflorix™ two-dose presentation. Specific pre-introduction measures are required to assure programmatic readiness is achieved prior to introduction. Post-introduction evaluations and corrective training actions, where needed, are required to assure appropriate continued use of this presentation.

Each country considering introduction of this vaccine presentation will need to ensure its programmatic readiness to do so. Each country will also need to ensure the monitoring of its correct use and implementation of any corrective training needed. To mitigate against potential programmatic risk countries should ensure that they:

  • Understand the benefits and potential contamination risks of the two-dose unpreserved presentation and understand the need for special training to enhance immunization worker practices.
  • Conduct post introduction evaluations to determine levels of Health Care Worker knowledge and compliance with the correct handling of the vaccine; and implement corrective training if needed.

Prior to introduction countries should:

  • Ensure training materials are in place in immunization centres prior to the launch of the vaccine.
  • Place stickers on refrigerators at all levels indicating that opened vials of the vaccine must be discarded six hours after opening. The stickers should be in place prior to the launch of the vaccine.

As per usual practice, the prequalification status of every vaccine is reviewed at regular intervals. The data gathered from introduction in further countries, together with the additional results expected in 2013 from the programmatic survey in Ethiopia, the two year safety study report from Kenya and the one year safety study report from Ethiopia will be referred to the WHO Programmatic Suitability for Prequalification Standing Committee (PSPQ SC) for review and advice, and be the basis for a further review of the prequalification status of this presentation of Synflorix™.

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.

Details can be found in a statement on Prequalification of one- and two-dose presentations of preservative-free 10-valent pneumococcal conjugate vaccine from GlaxoSmithKline (GSK) (Synflorix™):