The new Guideline on the Pharmacovigilance of Vaccines against infectious agents has been released for comments from Industry, healthcare professionals, patients’ organisations. The final release is planned for Q4 2013.
We have summarised below, for those of you who are less familiar with PV in Vaccines or Biologicals, some sections highlighting differences between pharmacovigilance (PV) practices in common medicinal products and PV in vaccines:
- unlike most medicines which are composed of relatively small molecules, vaccines are often highly complex multi-component products manufactured from biological systems that are inherently variable over time and between manufacturers (and sometimes between different production plants of the same manufacturer).
- vaccines are usually administered to otherwise healthy individuals, often very young or vulnerable; they may be administered to a large fraction of the population and vaccination is mandatory in some countries; there is therefore a high level of safety required for vaccines and tolerance to risk is usually low;
- assessment of causality between adverse events and vaccines may be difficult: several vaccines are often administered concomitantly, vaccination may be given in children at the age where some diseases may emerge, and considerations of de-challenge and re-challenge are not relevant to many vaccines which are administered only once or have long-term immunological effects;
- vaccines are complex biological products which may include multiple antigens, live organisms, adjuvants, preservatives and other excipients, and each of these components may have safety implications; variability and small changes in the manufacturing process, new components and new production and administration technologies may impact on safety, and this may require specific pharmacovigilance systems;
- the benefit-risk balance for vaccines also depends on factors acting at the population level, including the incidence, geographical distribution, seasonal characteristics and risk of transmission of the infectious disease in the target population, the proportion of infected persons with a clinical disease and the severity of this disease;
- concerns raised by the public may have a negative impact on the vaccination programme and should be adequately addressed;
- effective communication about safety of vaccines and vaccination is difficult, given the fact that perceptions of harm may persist despite evidence that a serious adverse event is not related to the vaccination.
Also, the Risk Management Plan for prophylaxis vaccines should address specific issues and additional PV activities may be needed in the following situations:
- to detect strain replacement phenomena (with genotyping of circulating strains as necessary) for vaccines that may protect against only some types of organisms within a species;
- to address the pattern of shedding, transmissibility to contacts and the potential of the strain to survive in the environment;
- to establish evidence of safety for novel vaccines, in particular in relation to long-term and delayed onset adverse reactions;
- to assess effectiveness of the vaccine, especially where pre-authorisation data are limited; in cases where a novel adjuvant has been incorporated into the vaccine formulation:
- to assess the risk of induction of rare or delayed onset adverse reactions, local or systemic; – to detect occurrence of auto-immune diseases and immune-mediated reactions resulting from a synergistic action of the adjuvant and the biologically active antigen.
Where additional investigations regarding the impact of different vaccination schedules are needed, it is acknowledged that it might not be feasible to study all recommended priming and booster schedules across the EU, but a rationale for further evaluation should be presented (e.g. studying the most accelerated schedule based on 2 or 3 doses).
When initiating an additional pharmacovigilance activity, the marketing authorisation holder should investigate the availability of systems for collecting data in different countries.
If you are a healthcare professional and would like to make comments to EMA through Pharma Design, please do not hesitate to contact us at the following address: