Pandemic Vaccination The actors Influenza vaccine manufacturing

The actors
Pandemic Vaccination
EMEA
Daniel Reynders MD, MPH
Symposium BICS 17 Octobre 2009
Influenza vaccine
manufacturing process and
timeline
Production process
•Key: The arrows with dotted lines preceded by non-broken arrows indicate the time period
required for the first time an activity is done (non-broken arrow line) that is then repeated
(dotted arrow line). The solid lines signify that the activity takes place within a finite period.
Production of influenza
interpandemic vaccines
Recommended composition of influenza virus
vaccines for use in the 2010 southern
hemisphere influenza season
Each year: 2 new vaccines
Choice of strains
F
Northern hemisphere
Southern hemisphere
M A
M
J
Vaccine on the market
J
A
S O
N D
J
PRODUCTION
PRODUCTION
F M
It is recommended that vaccines for use in the 2010
influenza season (southern hemisphere winter)
contain the following:
— an A/California/7/2009 (H1N1)-like virus;
— an A/Perth/16/2009 (H3N2)-like virus;
— a B/Brisbane/60/2008-like virus.
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Approval process for
Pandemic vaccine
What was expected for pandemic
vaccine?
Vaccine
Formulation
Prototype
vaccine
Industry
Pandemic
vaccine
The mock-up authorization
procedure
• A mock-up vaccine is a type of flu vaccine that is
developed well before a pandemic has started. Because the
strain of flu virus that will cause a future pandemic is not
known, pharmaceutical companies cannot start to prepare a
vaccine containing the correct flu virus until a pandemic
has started. To get around this problem, the mock-up
procedure (also known as the ‘core dossier’ procedure)
allows vaccine manufacturers to gain an authorisation for a
prototype pandemic vaccine in advance of a pandemic.
This approach is unique to pandemic vaccines.
Safety and effectiveness
PreClinical
Testing
Government
Buyers
Clinical
Testing +
Ab assays
Mock-Up
Registration
File
Production
Scale-Up
Production
Shipment &
Delivery
market
Assumptions for Mock-Up Vaccine
•
The immune responses to a specific mock-up vaccine containing a strain to
which subjects within a specific age range were immunologically naïve is
expected to predict responses to the same vaccine construct containing an
alternative strain of the same subtype or an alternative subtype of influenza A
in a comparable population.
•
The safety data generated with a specific mock-up vaccine in clinical studies
is expected to predict the safety profile observed with the same vaccine
construct containing an alternative strain of the same subtype or an alternative
subtype of influenza A in a comparable population.
•
The “Mock-up” pandemic influenza vaccine (core dossier) is a vaccine that
mimics the future pandemic influenza vaccine in terms of its composition
construct (antigen content, excipients, and adjuvant system, if used),
manufacturing and control. The mock-up vaccine is produced in the same way
as is intended for the final pandemic vaccine but it does not contain antigen
from the actual pandemic strain.
Summary
• Based on decades of experience with seasonal flu vaccines,
insertion of a new virus strain in a vaccine should not
substantially affect the safety or level of protection offered
by the final pandemic vaccine once it contains the
pandemic flu virus strain.
• To confirm that the final vaccines are as safe and effective
as expected, their effects will be closely monitored after
they have been authorised. This is especially important
for certain groups of patients for whom limited data are
expected to be available at the time of the final pandemic
vaccine’s authorization, such as children and pregnant
women.
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The pandemic vaccine for Belgium
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•
12.600.000 doses ordered to GSK
Pandemrix
Multi-doses vials (10 per vial)
Progressive delivery -> Phasing of
administration
What is Pandemrix?
• Pandemrix is a vaccine that is given by injection.
It contains parts of influenza (flu) viruses that
have been inactivated (killed). Pandemrix contains
a flu strain called A/California/7/2009 (H1N1) vlike strain (X-179A).
• The vaccine will be injected
into a muscle
(usually in the upper arm).
How has Pandemrix been studied?
• Pandemrix was first developed as a ‘mock-up’ vaccine,
using a H5N1 strain of the flu virus called
A/Vietnam/1194/2004. The company studied the ability of
this mock-up vaccine to trigger the production of
antibodies (‘immunogenicity’) against this strain of flu
virus in advance of the pandemic.
• Following the start of the H1N1 pandemic, the company
replaced the virus strain in Pandemrix with the H1N1
strain causing the pandemic, and presented data relating to
this change to the Committee for Medicinal Products for
Human Use (CHMP).
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What is the risk associated with
Pandemrix?
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•
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The most common side effects with Pandemrix (seen with more than
1 in 10 doses of the vaccine) are headache, arthralgia (joint pain),
myalgia (muscle pain), reactions at the site of the injection (hardening,
swelling, pain and redness), fever and fatigue (tiredness).
Pandemrix should not be given to people who have had an
anaphylactic reaction (severe allergic reaction) to any of the
components of the vaccine, or to any of the substances found at very
low levels in the vaccine, such as egg or chicken protein, ovalbumin (a
protein in egg white), formaldehyde, gentamicin sulphate (an
antibiotic) and sodium deoxycholate.
However, it may be appropriate to give the vaccine to these patients
during a pandemic, as long as facilities for resuscitation are available.
Marketing authorisation
• The European Commission granted a marketing
authorization valid throughout the EU for the
H5N1 mock-up vaccine for Pandemrix to
GlaxoSmithKline Biologicals s.a. on 20 May
2008.
• The change to the marketing authorisation for the
H1N1 virus was authorised by the European
Commission on 29 September 2009.
Adjuvants
• Définition : substances utilisées pour augmenter
l’efficacité des vaccins (Alum, MF59, AS04, AS03):
AS03
•
– Réduction des doses d’antigènes.
– Réponse immunitaire croisée.
• Adjuvants pour les vaccins grippaux :
– À base de squalènes (substance lipidique naturelle)
• MF59 (Novartis) : déjà utilisé dans le vaccin Gripguard® depuis
1997 (> 45 millions de doses)
• AS03 (GSK) : > 30 000 volontaires dans les essais cliniques en cours
(H5N1, grippe saisonnière, H1N1, malaria)
• AF03 (Sanofi Pasteur)
•
•
•
The AS03 adjuvant of GSK is also an oil-in-water emulsion. The oil phase
contains two oils, squalene, the same main component as MF59C.1 (natural
component of cell membranes), and DL-α-tocopherol (vitamin E). Nonclinical data are mainly derived from rodent studies, and raise no concern.
GSK has generated a significant amount of clinical data in adults and the
elderly and limited data in children aged 3-9 years with the H5N1 mock-up
vaccine. The AS03 adjuvanting system was associated with greater
reactogenicity compared to corresponding doses of HA alone but the safety
profile is still considered to be acceptable.
So far no safety signals have been detected that indicate an increased risk of
autoimmune disease following the use of these adjuvants.
A seasonal vaccine with the MF59C.1 adjuvant, Fluad, has been licensed for
use in elderly in the EU and used in some countries since 1997. More than 45
million doses of Fluad have been distributed since 1997. It is currently under
evaluation in children.
Clinical trials with several MF59C.1 adjuvanted vaccines have been performed
in different age groups including children from 6 months onwards
without raising safety concern
Usefulness of a vaccine for the
A/H1N1v pandemic (general)
Usefulness of a vaccine for the
A/H1N1v pandemic (children)
• The attack rate for the A(H1N1)v virus strain has been
estimated to be higher than for recently circulating
seasonal strains because of the lower levels of preexisting immunity in the population. Current estimates for
the attack rate associated with the influenza A(H1N1)v
virus over the first major wave of infection vary from
approximately 10 to 30 % in different geographical areas.
As a result, the actual numbers of clinically apparent
infections, cases that require hospitalization and deaths in
the pandemic period is expected to be higher than the
numbers seen in recent years for seasonal influenza. These
estimates may change (upwards or downwards) during the
course of the pandemic.
• Nearly 80% of cases are in individuals
under 30 years of age. Based on these
figures, ECDC in its recommendations has
included young children (especially those
below 2 years) in the risk groups for 2009
pandemic influenza and WHO has included
children above 6 months, particularly those
with chronic conditions, among the
priorities for vaccination.
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Usefulness of a vaccine for the
A/H1N1v pandemic (pregnancy)
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•
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From April 15 to May 17, 2009 in the USA, 553 confirmed or probable cases
of pandemic A(H1N1)v have been reported to the US CDC (Center for
Disease Control and Prevention). The estimated rate of hospital admission for
pandemic A(H1N1)v virus infection in pregnant women was higher
(approximately 4 fold) than in the general population in the first month of the
outbreak. Of a total of 266 deaths reported between April 15 and July 29,
2009, there were 15 pregnant women. All of them had developed pneumonia.
These data indicate that as in other pandemics, pregnant women appear
to be at increased risk for severe complications from the pandemic
A(H1N1)v virus infection.
The burden of disease in pregnant women during epidemics and pandemics
has been consistently shown to increase with the progression of pregnancy and
the presence of co-morbidities.
Based on the observed and the expected epidemiological pattern, ECDC and
WHO have recommended the inclusion of pregnant women, regardless of
the stage of pregnancy, amongst priority groups for pandemic
vaccination.
Qui ?
groupes à risque
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Les groupes à risque prioritaires pour la vaccination sont les mêmes que ceux
définis pour l’administration d’antiviraux :
Les patients atteints d’une maladie chronique affectant la fonction respiratoire
comme les patients atteints d’asthme sévère, BPCO, mucoviscidose, bronchodysplasie…
Les patients souffrant d’une pathologie cardiaque chronique à l’exception
d’hypertension non compliquée ;
Les patients diabétiques ;
Les patients porteurs de pathologies neuromusculaires chroniques ;
Les patients qui souffrent d’une atteinte neurologique sévère (par ex: paralysie
cérébrale)
Les patients atteints d’une insuffisance rénale ou hépatique modérée à sévère ;
Les patients immunodéprimés suite à une maladie ou un traitement ;
Les patients porteurs de désordres métaboliques héréditaires.
Qui ?
groupes prioritaires
•
•
Outre les groupes à risque, d’autres groupes sont encouragés à se faire
vacciner de par leur proximité possible plus élevée que les autres citoyens avec
le virus. Il s’agit :
des autres dispensateurs de soins et personnel des institutions de santé agréés :
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–
–
–
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•
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Infirmiers à domicile
Personnel de la Croix-Rouge
Médecins du travail
…..
Pourquoi ?
• Maintenir le système de santé fonctionnel
• Diminuer les complications et la mortalité
• Eviter un effet Domino
des femmes enceintes (au deuxième et troisième trimestre) et des femmes
inscrites dans un programme de procréation assistée
des parents d’enfants de moins de 6 mois ou des personnes en ayant la garde
du personnel d’encadrement des crèches, écoles maternelles, écoles primaires
et secondaires.
Où et Quand ?
Où et Quand ?
• Phase 1
– Vaccination uniquement dans les institutions
hospitalières pour tout leur personnel et les
étudiants en médecine et élèves infirmiers.
– Quantité de vaccin disponible espéré : +/500.000 au 18/10
– Effectif estimé : <200.000
– Date programmée de démarrage : 18/10/2009
• Phase 2
– Démarrage de la vaccination par les médecins
généralistes sur la base de l’ordre de priorité repris cidessous
– Critères de démarrage : 1 million de doses disponibles
(ce qui correspond +/- à 100 doses vaccinales par MG,
soit à une capacité de vaccination de +/- 15 jours). Le
rythme d’approvisionnement ultérieur programmé
devrait permettre d’éviter des ruptures de stocks.
– Date estimée de démarrage début novembre 2009 en
fonction de la réception des vaccins.
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Priorités pour les MGs
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les dispensateurs de soins non- hospitaliers, en ce compris le
personnel de la Croix-Rouge
les personnes présentant une pathologie préexistante les définissant
comme à risque de complications de moins de 65 ans
les personnes de plus de 65 ans à risque
les femmes inscrites dans un programme de procréation assistée
les femmes enceintes au deuxième et troisième trimestre
les parents d’enfants de moins de 6 mois ou les personnes en ayant la
garde
le personnel d’encadrement des crèches, écoles maternelles, écoles
primaires et secondaires
Quelles doses ?
•
Adults, including the elderly
– A dose (0.5 ml) of the vaccine will be given.
– A second dose of 0.5 ml vaccine may be given after an interval of at least three
weeks.
•
Children and adolescents 10-17 years of age
– If it is considered that you need to be vaccinated, you may receive two doses of 0.5
ml vaccine given at least three weeks apart.
•
Children aged from 6 months to 9 years of age
– If it is considered that your child needs to be vaccinated, he/she may receive one
dose of 0.25 ml vaccine and a second dose of 0.25 ml at least three weeks later.
•
Children aged less than 6 months of age
– Vaccination is currently not recommended in this age group.
Questions en suspens…
• Une dose ou deux doses
• Phase 3 de vaccination ?
• Pic pandémique et donc l’utilité de la
vaccination
• Couverture vaccinale
Il n’y a jamais UNE solution mais des choix qu’il faut faire
Je vous remercie…..
Pour de plus amples
informations:
informations:
www.influenza.be
0800 99 777
… d’autres questions?
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