Ninth European Medicines Agency pandemic pharmacovigilance weekly update
http://www.ema.europa.eu/pdfs/influenza/7111610en.pdf
3 February 2010

Description:
This update, the ninth in the series published by the European Medicines Agency (EMA) provides a summary of the progress of vaccination with pandemic vaccines in Europe with particular emphasis on pharmacovigilance and safety.  It records that as of 1 February 2010 at least 35.7 million people, including a minimum of 261,000 pregnant women, had been vaccinated in Europe with one of the three centrally authorised vaccines (Celvapan, Focetria or Pandemrix). When the information available for the nationally authorised vaccines is included, the larger total is at least 40.2 million people in Europe. Some of these have received two doses of a vaccine, but the percentage varies across countries.  The report notes that all of the adverse reactions considered to be related to vaccination reported as of 24 January 2010 are non-serious and consistent with what was observed from the pre-licensure trials. Typically they are self-limiting swelling and soreness at the vaccine site or mild short-term general malaise or headache 
The Agency continues to consider the benefit-risk balance of the pandemic vaccines being used for the 2009 pandemic is strongly positive.  None of the serious adverse events following Immunisation (AEFIs), including deaths, that have been fully investigated are considered to be due to immunisation. Because there is a constant background rate of such adverse events there are a number of these cases under investigation by national authorities and the EMA. 
The report focuses on reactions and AEFIs reported after the use of the three centrally authorised pandemic vaccines – Celvapan, Focetria and Pandemrix – and events following use of the the antiviral Tamiflu (oseltamivir). The report also provides information on the evolution of the H1N1 pandemic, an estimate of how many doses of vaccines and antivirals have been distributed or administered in Europe, and other available information on the benefits and risks of the vaccines and antivirals. The report explains how the reactions do not have to be necessarily caused by the medicines but, they can be a symptom of another illness or they could be associated with another product taken by the patient. Additionally, the report points out that due to differences in the numbers of people receiving each vaccine, the number of reports shown for the three different vaccines cannot be used to compare the safety or the benefit-risk balance of the vaccines.

ECDC comment (February 4th 2010):  The safety of the new pandemic vaccines continues to be a prime concern to the authorities and the public. Pandemic vaccines from the European manufacturers used in on-going clinical trials in healthy children, adults and elderly have so far been well tolerated with only minor side effects. The authorised H1N1 vaccines undergo the same rigorous manufacturing oversight, product quality testing and lot release procedures that apply to seasonal influenza vaccines. Some lots have been withdrawn as a precaution in North America but not in Europe, because of lack of potency but not lack of safety.

At this stage longer-term safety data cannot be available and associations with rare conditions are only being ruled out by this careful post-marketing surveillance. This is always the case with new vaccines and medicines in general at the moment of their introduction.  Post marketing surveillance is taking a number of forms. The routine spontaneous pharmacovigilance system within EU Member States has been continue with reports going as usual to the EMEA Eudravigilance database the output of which are appearing in the pharmacovigilance report. In addition national regulatory authorities are putting sometimes more detailed reports into the public domain. As another check Manufacturers are required to send simplified periodic safety update reports to the EMA on a monthly rather than a six monthly basis. In addition, ECDC with a consortium of researchers (VAESCO) has been developing complementary vaccine safety monitoring and hypothesis-testing through linkage of large computerised clinical databases and immunisation registries. To date all these data, which are repeated in monitoring elsewhere coordinated by the World Health Organization are reassuring.(1) Those monitoring vaccine safety have been keeping a special watch for increased incidence of Guillain-Barre syndrome (GBS) and a number of other rare conditions the background rates of which have been established for Europe by the VAESCO project.(2) The overwhelming evidence, including the best study to date in Europe points to no association of GBS with seasonal influenza vaccines, but instead a documented significant association of GBS with influenza infection itself.(3)  Finally it is illustrative to compare the mortality directly linked to the pandemic vaccines and to the pandemic virus in Europe. To date (the start of February 2010) the independent EMEA report has found no fatalities that can be directly linked to vaccination while the EU/EEA member states have reported more than 2500 deaths they attribute to infection with the pandemic virus.(4)  

 
1. WHO Statement from WHO Global Advisory Committee on Vaccine Safety about the safety profile of pandemic influenza A (H1N1) 2009 vaccines http://www.who.int/csr/resources/publications/swineflu/gacvs_statement_20091218/en/index.html

2. Eurosurveillance editorial team.  ECDC in collaboration with the VAESCO consortium to develop a complementary tool for vaccine safety monitoring in Europe. Euro Surveill. 2009 Oct 1;14(39). pii: 19345. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19345

3. Stowe J , Andrews N, Wise L, & Miller E. Investigation of the Temporal Association of Guillain-Barré Syndrome With Influenza Vaccine and Influenzalike Illness Using the United Kingdom General Practice Research Database. American Journal of Epidemiology Am. J. Epidemiol. 169: 382-388.
http://aje.oxfordjournals.org/cgi/reprint/169/3/382

4. Executive report this week