Global Vaccine Safety

Global Advisory Committee on Vaccine Safety, report of meeting held 15-16 June 2011

Published in the WHO Weekly Epidemiological Record on 22 July 2011

The Global Advisory Committee on Vaccine Safety (GACVS), an expert clinical and scientific advisory body, was established by WHO to provide independent, scientifically rigorous advice on vaccine-safety issues of potential global importance.1 GACVS held its 24th meeting in Geneva, Switzerland, in June 2011.2 The Committee reviewed (i) new data on the safety profile of meningococcal A conjugate vaccine, (ii) a new approach for assessing the causes of serious adverse events following immunization (AEFI), (iii) preparation of information sheets describing the safety profile of important vaccines, and (iv) the development of global strategies to enhance capacity to monitor and respond to vaccine-safety issues in low-income and middle-income countries.

Safety profile of meningococcal A conjugate vaccine

GACVS received updated data on vaccine safety from campaigns to introduce MenAfriVac meningococcal A conjugate vaccine in the 3 countries (Burkina Faso, Mali and Niger) where the vaccine was introduced during December 2010. Previously, data presented from 7 phase I and phase II clinical trials at 5 sites (the Gambia, Ghana, India, Mali and Senegal), and from the pilot introduction of the vaccine in September 2010, had not indicated any cause for concern about the safety of this lyophilized vaccine. The pilot phase was followed by introduction of the vaccine into all 62 districts in Burkina Faso, 20 districts in Mali and 11 districts in Niger, covering a total population of almost 18 million: 10.7 million in Burkina Faso, 4.5 million in Mali and 2.7 million in Niger. Following a recommendation made by GACVS prior to the December 2010 rounds, an active surveillance component has been included in 1 district in Burkina Faso in addition to the enhanced passive surveillance system already in place.

Passive surveillance revealed a total of 1807 AEFIs, including 44 serious events, reported from 18.4 million people vaccinated in the 3 countries during introduction. This corresponds to a reporting rate of 9.8 AEFIs per 100 000 people vaccinated. Fever (39.2%) and local reactions (28.4%) were most commonly reported. Based on a review by national expert Committees in each country, only 3/44 serious AEFIs were classified as possibly or probably related to vaccination (1 case each of acute exanthematous pustulosis, bronchospasm, and vomiting). In addition, during the pilot phase another 4 serious events were classified as possibly or probably related to vaccination (bronchospasm, meningitis-like syndrome, vomiting, and urticaria). Active surveillance for 12 pre-identified syndromes was conducted for 52 days (10 days during the vaccination campaign and 42 days after) in 16 health-care facilities in which approximately 100 000 people had been vaccinated. A total of 71 episodes of these syndromes were investigated, of which the most common were convulsion (32 cases), urticaria (18) and bronchospasm (14). The national expert Committee of Burkina Faso classified these cases as coincidental. For the 3 most frequent syndromes, the distribution of the intervals between vaccination and the occurrence of symptoms did not reveal any temporal clustering.

A total of 2022 pregnant women vaccinated in Burkina Faso and Mali are also being followed to collect data on AEFIs and pregnancy outcomes.

GACVS concluded that the data from surveillance during the introduction of MenAfriVac do not indicate any reasons for concern about the vaccine’s safety. However, reports of bronchospasm and urticaria may suggest hypersensitivity reactions to vaccination, and the Committee recommended that a more in-depth review of these cases be made to rule out anaphylaxis.

GACVS recognized that it would not be practical to conduct widespread active surveillance but highlighted the need for AEFI surveillance to continue as the vaccine becomes more widely available, so that additional information about its safety profile can be obtained.

Causes of adverse events following immunization

In December 2010, in view of the difficulties many countries have had in evaluating individual cases or clusters of AEFIs, GACVS convened a group of experts to review the WHO guidelines on assessing the causes of serious AEFIs. The guidelines are intended to be used for assessment of individual cases of serious AEFIs in order to evaluate whether they are related to vaccination. The review is in progress. Its aim is to develop a simple, objective, transparent and evidence-based approach to help national and regional authorities determine whether a serious AEFI reported through pharmacovigilance is likely to have been caused by a specific vaccine.

The new method for assessing AEFIs will be based on previous experience with specific vaccines. However, it is clear that the evaluation of serious AEFIs not previously associated with a specific vaccine will require other approaches, including epidemiological studies to identify the frequency, distribution and presentation of an event, and to investigate whether an event is associated with vaccination.

GACVS also emphasized that AEFI surveillance systems must be strengthened at country level and regional level to improve the reporting of safety signals following immunization.

Information about rates of reactions to vaccines

WHO is developing information sheets that will summarize what is known about the rates of reactions following administration of specific vaccines. The information sheets are part of a series that will be made available on the WHO web site; their aim is to support national and regional regulatory health authorities as well as the staff of immunization programmes. The information sheets can be used as resources during the analysis, investigation and review of possible reactions to vaccines.

A range of experts are collaborating with WHO to develop and review the information sheets. As part of this process GACVS reviewed a draft introduction and 2 draft information sheets that provide data on rates of reactions following immunization with Haemophilus influenzae type B vaccine and bacille Calmette–Guérin vaccine. The introduction outlines how the information sheets have been developed.

GACVS supports this initiative and recognizes the value of this resource. GACVS acknowledged that the information sheets are being developed from data derived from literature reviews and expert review rather than from a systematic review of data on each vaccine. GACVS recommended that the introduction describe the methods that have been used to develop the summaries so they can be interpreted appropriately.

The process of reviewing the information sheets and the role of GACVS was discussed. It was decided that each information sheet will be reviewed by experts. Subsequently, each revised information sheet will be reviewed by 2 GACVS members who will make final recommendations to the chair of GACVS regarding the release of the information sheet. It is expected that this process will be completed by early 2012.

Developing a global strategy for enhancing vaccine safety

The need for effective systems to monitor the safety of vaccines and to respond to safety issues in low-income and middle-income countries has been broadly recognized.3 To respond to this demand, WHO is coordinating the development of a strategic plan. An early version of this plan, the “global vaccine safety blueprint,” was discussed by GACVS. The plan will: (i) assist all low-income and middle-income countries in developing at least a minimal capacity to effectively monitor vaccine safety and respond to safety signals, (ii) enhance the level of active surveillance of vaccine safety in countries that introduce new vaccines, and (iii) foster international collaboration and encourage strategic planning so that all vaccines receive adequate safety surveillance and that safety information is shared internationally.

GACVS identified several elements of the blueprint that could be strengthened. It is important that vaccine programmes evaluate vaccine safety as part of their assessments of benefits and risks. Therefore, developing the capacity to monitor the effectiveness of vaccines in preventing targeted diseases should also be a high priority. A monitoring system for vaccine safety should be designed to detect potential safety problems and respond to them rapidly. It is necessary to create and coordinate the capacity for appropriate epidemiological investigations to be undertaken in response to potential safety signals at country level or intercountry level. Several networks with the relevant capacities exist, and WHO will have a critical role in convening and coordinating these groups. In addition, because investigating safety issues requires close interaction with manufacturers, the blueprint should include a code of conduct to be followed during interactions with the pharmaceutical industry. It will also be important to ensure that a proportion of national budgets for vaccines include funding for assessing and investigating safety because these duties will be fundamental to sustaining the development of safety systems. Finally, because many advanced monitoring and investigational activities require access to patients’ information, the blueprint should promote implementation of regulations on data protection that will allow for secondary use of health-care data for public health purposes, including the sharing of data among countries.

The WHO Secretariat and collaborating experts are preparing a version of the draft strategic plan that will be available to all who are considered stakeholders in global vaccine safety and will take into account advice received from GACVS and other stakeholders. It is planned to release this draft during the second half of 2011.

  • See No. 41, 1999, pp. 337–338.
  • GACVS invited additional experts to present and discuss evidence related to particular topics. These experts included people affiliated with Bambino Gesù Hospital, Rome, Italy; the Ministry of Health, Ouagadougou, Burkina Faso; and University Children’s Hospital, Basel, Switzerland.
  • Global Advisory Committee on Vaccine Safety (GACVS), WHO secretariat. Global safety of vaccines: strengthening systems for monitoring, management and the role of GACVS. Expert Review of Vaccines, 2009, 8:705–716.