Transcript VHPB - Malta 22-23 October 2001

VHPB - Malta
22-23 October 2001
Summary conclusions:
1: Generalizations
2: Drawbacks, concerns and issues
3: Data and information
Goals of vaccine programmes
• Prevention and control of disease, also
eradication/elimination of pathogens
• Successes:
– eradication of smallpox
– progress towards eradication of poliomyelitis,
measles, and other disease
– progress towards control of hepatitis B and Hib
Vaccines
• Safe and effective
– most cost-effective medical and public health
intervention against infectious diseases
– hepatitis B vaccine: one of the safest and most effective
vaccines ever developed
• Development time reduced
• Need for high-quality and affordable
vaccines
• Costs falling or can be reduced through
cooperative bidding and other mechanisms
Combined vaccines
• Not new (e.g. influenza (AAB), OPV 1, 2 &
3, DTP, MMR, bacterial + viral vaccines,
polyvalent vaccines)
• Accelerated development and licensure,
despite complexities
• Safe and immunogenic
• Effective - reducing disease and not altering
pathogen circulation
Combined vaccines - continued
• Agreed principles for administration
– e.g. acceptability of giving an extra dose of
antigen
– non-interchangeability of vaccines from
different manufacturers
• Quality assurance secured
– accreditation of quality control laboratories
(ISO system)
– EU release certificate
– Audits (EDQM, WHO - national regulatory
authorities and manufacturers)
Benefits
• Simplified immunization programme
implementation
• increased acceptance, decreased global cost,
increased disease control
• decreased disease prevalence and burden
• fewer health service visits and lower
programme costs
• increased vaccine coverage
Benefits - continued
• Reduced number of injections per visit and
fewer injections given overall
– reduced waste
– increased safety - although limited role of
combination vaccines in developing countries
– less or no exposure to thiomersal
• lower costs of storage, transport, cold chain
(except developing countries)
Benefits - continued
• harmonization of antigens
• ease of adding new antigens in existing
programmes
• data collection facilitated and
documentation eased
Drawbacks, concerns and issues
• Wide variation in immunization schedules
across Europe and compared with USA
– national and federal approaches
– different epidemiological patterns
– issues of compulsory/obligatory and voluntary
immunization
– testing of each formulation for each
immunization schedule in EU - ethical issues
– school entry requirements
Immunization schedules
• history of attempts to harmonize
• cross-roads in decision-making process
• consequences for local production and
global vaccine supply (e.g. DTP shortage
and monovalent HB glut)
• change in antigens (Pw  Pa, OPV  IPV)
• maternal screening and routine
immunization of newborns - unnecesary?
Legislation and regulatory issues
• Licensing, availability, usage - not the
same
• EU-wide licensing, but trials for each
schedule
• licensing of components, new formulations,
increasingly complex with polyvalent Vs
• post-marketing conditions
• need to assess models for combined Vs
Legislation and regulatory issues
- continued
• Legislation needs to be adapted to introduce
new vaccines/antigens
– inflexibility of programmes
• Regulations for bidding and procurement
• Compulsory immunization and legal
consequences
– legislation more powerful than education of
physicians in driving immunization of
schoolchildren
Legal and regulatory issues
• Thiomersal issue - lawsuits in litigious
societies
• manufacture of vaccines in industrialized
countries for use in developing countries
– role of national regulatory authorities in
developing countries
– flexibility of some countries (e.g. Italy)
Clinical development and trials
• Increasing complexity and cost
– each component to be tested for safety and
efficacy
– number of arms increases exponentially with
number of components, leading to trials with
huge numbers of participants to test against
different immunization schedules - “unethical”
• Interference (immunological and chemical)
Clinical development and trials continued
• Need to establish new minimum potency
and protection levels
• Need for new reference materials
• Analysis of adverse reactions
• Surrogate markers
Financial issues
• Prices
• combined vs monovalent
• premiums (e.g. Latin America)
• trade off: fewer injections and side effects vs price
• Who pays for vaccines and immunization?
– Public/private sectors
– Incentives (physicians/families)
• Which vaccines are paid for by state?
– Wide variations in EU, USA...
Economic issues
• Lower administrative costs
– time of vaccinators
• less pain for children, and parents save time
and money
• high willingness to pay for reduction from 4
to 3 and 2 to 1 injections
• Complexity of health insurance. EU
Funding mechanisms
• Global Alliance for Vaccines and
Immunization (GAVI)
• Pan American Health Organization-type
revolving funds
• Other
Hexavalent combined vaccines
• Advantages:
–
–
–
–
increased compliance,
increased vaccine coverage,
facilitated data collection,
decreased costs compared to sum of separate
vaccines (at least in Germany),
– decreased storage and logistic requirements
Hexavalent vaccines - continued
• Quality issues (intermediates)
• Efficacy
• “Combination is more than mixing”
• need for better/other markers of protection
• Formulation issues
• liquid, powder
• Hib responses may be lower, but are protective
(possibly related to pertussis component)
Hexavalent vaccines - continued
• Issues
– how long does protection last?
• few breakthrough infections - hepatitis B
– memory immunity
• variations in immunogenicity
• reasons for reduced immunogenicity (ethnic
differences in Sweden)
• increased likelihood of adverse reactions?
• limits to number of antigens?
Manufacture and supply
• Sole-source supply/source of antigens
• Reliability of manufacturers to fulfil
contracts or deliver
• Procurement and bidding practices
• Pre-qualification/availability
• Manufacturers’ responses - strategic
alliances (e.g. purchase of national
companies)
New data
• “Combining is more than mixing”
• Country updates - Europe is more than EU
– Belgium, Finland, France, Germany, Israel,
Italy, Lithuania, Switzerland, Turkey, USA
• How anti-HBs protects
• Genetic correlates of non-response to HB
– strategies to overcome non-responsiveness
• Production process
• HB immunization schedules in Europe to be
further updated
Data needed
• Vaccine production capacity
• Manufacturers’ (general) future plans
• Demand forecasting and data (national
immunization programmes)
• Disease burden/demographic data (e.g.
births on developing countries)
• Reasons for decreased immunogenicity of
components in combined vaccines
Data needed
• Science
– Reasons for decreased immunogenicity of
components in combined vaccines
– HB virus-binding site on hepatocytes
– Mechanisms of action of anti-HBs
– Mucosal immunity
• Economic evaluation of combined vaccines
Information and communication
• Reasons for non-vaccination
– insufficiency of information about diseases, vaccines
and immunizations - parents’ view
– missed appointments - common reason
– doctors do not propose or recommend immunization
– ideological opposition to vaccines - rare
• Increase public sensitivity to safety issues
• Campaigns needed
– on benefits and safety of vaccines and combined
vaccines
– dispel myths (antigenic exhaustion/overload)
Information and communication
• Campaigns (cont)
– targeted at
• whole medical community
- training in medical schools
- particular focus on paediatricians, family physicians, practice
nurses, health care workers
• industry and professionals
• parents
• media (for balanced information)
• Close communication and coordination between
manufacturers and health authorities
• WHO vaccine use database
Conclusions
• Combined vaccines with hepatitis B
component are:
– safe, effective, licensed, available, used, not
(yet) cheap
– present challenges and opportunities
– added value
– likely demand from parents, health-care
workers and decision makers
– German recommendation: “use whenever
possible and applicable”