Vaccine Pharmacovigilance – Introduction

Vaccination is one of the great public health achievements of human history. Vaccines used in national immunization programmes (NIPs) are considered safe and effective when used correctly. Vaccines are, however, not risk-free and adverse events will occasionally occur following vaccination. Although most adverse events are minor (e.g. redness at injection site, fever), more serious reactions (e.g. seizures, anaphylaxis) can occur at a very low frequency.

There is a greater need to detect and investigate any adverse event following immunization (AEFI) than is generally expected for other pharmaceutical products due to lower  tolerance for risks from vaccines. Vaccines undergo several steps of evaluation to assess their safety and efficacy in clinical trials. Once introduced, vaccines undergo very thorough and continuous reviews of their manufacturing process and national regulatory authorities continue to monitor and investigate adverse events following immunization to ensure that they are safe for the entire population.

• According to the CIOMS/WHO Working Group on Vaccine Pharma­co­vi­gilance, Vaccine pharmacovigilance is defined as. “the science and activities relating to the
  • Detection,
  • Assessment,
  • Understanding and
  • Communication of adverse events following immunization and other vaccine- or immuni­zation-related issues, and to the prevention of untoward effects of the vaccine or immunization”

An adverse event following immunization (AEFI) is any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. AEFIs are divided in 5 categories. 

• Vaccine product-related reaction: An AEFI that is caused or precipitated by a vaccine due to one or more of the inherent properties of the vaccine product.
  • Example: Extensive limb swelling following DTP vaccination.
• Vaccine quality defect-related reaction: An AEFI that is caused or precipitated by a vaccine that is due to one or more quality defects of the vaccine product including its administration device as provided by the manufacturer.
  • Example: Failure by the manufacturer to completely inactivate a lot of inactivated polio vaccineleads to cases of paralytic polio.
• Immunization error-related reaction: An AEFI that is caused by inappropriate vaccine handling, prescribing or administration and thus by its nature is preventable.
  • Example: Transmission of infection by contaminated multidose vial.
• Immunization anxiety-related reaction: An AEFI arising from anxiety about the immunization.
  • Example: Vasovagal syncopein an adolescent during/following vaccination.
• Coincidental event: An AEFI that is caused by something other than the vaccine product, immunization error or immunization anxiety.
  • Example: A fever occurs at the time of the vaccination (temporal association) but is in fact caused by malaria. Coincidental events reflect the natural occurrence of health problems in the community with common problems being frequently reported.

Points to consider for vaccine pharmacovigilance: 

1. The benefits of immunization may not be immediately visible, particularly if the target disease incidence is low.
2. Due to the low acceptance of risks, intensive investigation of serious AEFIs, even if rare, is necessary.
3. Non-serious AEFI’s also should be carefully monitored because they may signal a potentially larger problem with the vaccine or immunization, or have an impact on the acceptability of immunization in general.
4. Appropriate methods are needed to detect and assess any potential causal association of serious, rare, and/or delayed adverse events, or of adverse events in subgroups, with immunization.
5. Consideration of dechallenge and rechallenge differs for vaccines compared with other medicinal products. Vaccines are frequently administered only once or with long intervals, and serious AEFIs often prevent further vaccine administration; hence rechallenge information is only rarely available. Dechallenge may not be applicable to vaccines, given their long-term immunological effects.
6. Vaccines are often administered concomitantly with other vaccines, making causal attribution to a specific vaccine difficult.
7. The administration of live vaccines can lead to disease caused by the attenuated organisms in vaccinees or their contacts; this should be differentiated from coinciding natural infection.
8. Vaccines are complex biological products, which may include multiple antigens, live organisms, adjuvants, and preservatives. Each component may have unique safety implications. Variability and (even small) changes in the manufacturing process may have impact on quality, protective effect, and safety. Batch information is of crucial importance.
9. New vaccines are increasingly based on new production and administration technologies, with new adjuvants and alternative routes of administration, necessitating adapted safety monitoring systems.
10. Depending on the mode and extent of use of a vaccine, it may elicit a degree of herd immunity to a specific disease. When assessing the risk-benefit of a vaccine, herd immunity effects as well as individual protection need to be taken into account.
11. Effective communication regarding the safety of vaccines and immunization is challenging. Despite strong evidence that a serious adverse event is not related to immunization, perceptions of harm may persist and may potentially have a negative impact on immunization of the population.