Combined hepatitis B vaccines (2001)

Benefits of combined vaccines

• Reduced number of injections per visit, and reduced total number of injections overall, leading to:
  -         Reduced number of exposures to possible injection pain;
  -         Less or no exposure to thiomersal;
  -         Less time spent in doctor visits;
  -         Less waste and increased injection safety with fewer syringes;
  -         Reduced immunisation programme costs.
• Improved vaccination coverage;
• Simplified implementation of immunisation programmes;
• Facilitated addition of new antigens into existing immunisation programmes;
• Facilitated harmonisation of antigens;
• Decreased disease prevalence and burden;
• Facilitated data collection through easier documentation;
• Reduced costs of storage, transport, cold chain (not valid for developing countries);
• May present a new opportunity to move towards harmonising vaccination calendars in the European Union.

Combined vaccines - drawbacks and issues

• Possible barriers to the use of certain combination vaccines based on complex issues regarding harmonisation of European vaccination schedules are due to:
  - Different epidemiological patterns per country / region;
  - Different national recommendations for compulsory and facultative immunisations;
  - Different national traditions and attitudes towards health care reimbursement;
  - Complexity of policy and decision making at national level involving many associations of physicians and health insurance providers.
• Potential decrease in immunisation programme flexibility with increase in number of antigens per dose.

• Shrinking market of vaccine manufacturers (due to mergers) places immunisation programmes at potential risk if a manufacturer of a combined vaccine chooses to stop production and no other supply source exists.
• Increasing complexity and costs of clinical development and trials involving:
  - Need for testing safety and efficacy of each vaccine component;
  - Ethical implications in conducting clinical trials with huge numbers of participants to test against different immunisation schedules;
  - Need to establish new minimum potency and protection levels;
  - Need for new reference materials;
  - Analysis of adverse reactions;
  - Surrogate markers.
• Combined vaccines with a hepatitis B component cannot be used for newborn immunisation since the nonhepatitis B components of combination vaccines have reduced immunogenicity in children less than six weeks of age. The monovalent hepatitis B vaccine must continue to be used as the birth dose.
• More long-term studies will be needed to evaluate when booster vaccinations are needed using hexavalent vaccines with a hepatitis B component, especially in immunisation schedules with only three vaccinations in the first year of life with no booster vaccination.
• Quality issues of hexavalent vaccines focus on the cumulative stability of vaccine intermediates, resulting in the Committee for Proprietary Medicinal Products (CPMP) recommendations that have been accepted by manufacturers in assuring that intermediates exceeding a certain age will not be used in the manufacture of vaccines.
• Efficacy issues highlight the need for establishing better or other markers of protection.
• While immunological responses against Hib may be lower in hexavalent vaccines, they still remain at clinically acceptable protective levels.

References

Viral Hepatitis Prevention Board. Combined hepatitis B vaccines. Viral Hepatitis Prevention Board meeting, St Julians, Malta, October 22-23, 2001. Viral Hepatitis 2002; 10.2.