Safety of pandemic influenza vaccines
At its request, GACVS was presented with historical experience from the 1976 swine influenza A (H1N1) outbreak and vaccination efforts initiated at the time in the United States. A number of lessons learnt from this experience should be taken into consideration in preparation for a potential pandemic. Vaccines from different manufacturers may behave differently in terms of safety or immunogenicity due to use of different viral strains, formulation or manufacturing processes. Possible high-risk shortcuts in response to a potential emergency would be difficult to justify prior to the actual occurrence of the emergency. Effectiveness of pandemic vaccines will not be known before the pandemic and possibly only after it is over. In addition, unexpected adverse events, whether coincidental or vaccine-related, will occur that may lead to anxiety and may affect vaccine uptake. It will be important to try to obtain appropriate baseline data in different age groups before the use of the vaccines or the onset of pandemic, to conduct a careful and independent regulatory review, updated, as new information becomes available. In this respect, WHO could play a critical role in assisting Member States and reviewing data from various sources for the evaluation of the available safety evidence. Clear communication on risks and benefits of immuno-prophylaxis is critical. A comprehensive set of the lessons and action points can be accessed on the web site at http://www.who.int/vaccine_safety/topics/en/.
The GACVS reviewed possible actions to overcome obstacles relating to the use of newly formulated vaccines for emergency use, some of which will contain new adjuvants. These include strengthening rapid detection systems for identification of AEFIs, testing and improving existing national and global networks for sharing of such information, and strong national regulatory oversight of the production facilities. The Committee was informed of a process initiated for the development of post-marketing surveillance protocols for pandemic influenza vaccine. The protocol and international information-sharing should be tested and harmonized during the forthcoming and subsequent influenza seasons. WHO’s role in gathering information on the safety profile of candidate pandemic vaccines from clinical trials should be enhanced. With regard to efficacy and safety testing, use of individual and cluster randomized trials was discussed from both practical and ethical standpoints. Such trials offer best quality of evidence and should be considered in the situation of limited vaccine supply. Internationally coordinated preparatory work for these trials should start immediately, as little time would be available for putting the needed infrastructure in place after the start of the pandemic.
Pregnant women are considered at special risk for influenza infection based on morbidity and mortality from previous pandemic events and from intense influenza seasons. The Committee reviewed the use of inactivated seasonal flu vaccine in 2003 1 and concluded that the risk–benefit of influenza vaccination during all stages of pregnancy should be reconsidered, given the high risk to the mother – and thus to the fetus – of the disease itself, and the likely small risk to mother and fetus of the inactivated influenza vaccine. There are currently no data on the safety profile of candidate pandemic influenza vaccines when administered during pregnancy. Where appropriate (e.g. with use of novel adjuvants), reproductive toxicity studies using animal models should be conducted. It is expected that inadvertent immunization during pregnancy may occur during the pre-pandemic phase of vaccine use. These pregnancies should be followed up and pregnancy outcomes (with or without adverse events) reported to pharmacovigilance centres. Pregnancy and congenital malformation registries should be scrutinized for ability to provide information on immunization events during pregnancy and linked to other databases enabling the review of safety outcomes in mothers and infants exposed to pandemic influenza vaccine during pregnancy.
1. See WER No. 79, 2004, pp. 16-20