METHOD OF STORING A VACCINE CONTAININGAN ALUMINUM
ADJUVANT
The present invention relates to a method for reducing and/or decelerating the
desorption of an antigen that has been adsorbed on an aluminum adjuvant as well as
to the product thereof - namely the combination of a vaccine composition
comprising the antigen adsorbed on the aluminum adjuvant and a container for the
composition, said container having particular characteristics.
A large number of antigens are able to adsorb on an aluminum adjuvant, in particular
at neutral pH or at a pH close to neutrality, which is the pH naturally required for
compositions that have to be administered to mammals, including humans.
Provided that the amount of adjuvant is such that the antigen can actually adsorb on
the adjuvant in an optimum amount when the two compounds are mixed together, the
maximum degree of adsorption is very frequently achieved. However, over time,
depending on the environmental conditions, the percentage of adsorbed antigen
(adsorption rate) may decrease, and this desorption may constitute an instability
factor.
Known environmental conditions that can affect the percentage of adsorbed antigen
(adsorption rate) include, for example, variations in pH (even slight variations), and
the addition of one or more medium component(s) or one or more additional
antigen(s) that may compete with the first antigen for the adsorption sites on the
adjuvant.
Conventionally, a ready-to-use multi-dose vaccine composition is loaded into vials,
e.g., glass vials closed with a plastic stopper. Similarly, a single dose of a vaccine
composition may be loaded in a mono-dose vial or a ready-for-injection syringe
consisting, in a standard manner, of a reservoir containing the vaccine, a plunger that
closes the reservoir at its distal end, and a device for administration, such as a needle
attached at its proximal end. According to an alternative standard filling mode, the
vaccine dose may also be loaded in a needleless syringe to which the practitioner
adds a separately packaged needle at the time of the injection. The reservoir of the
syringe is generally made of either glass or plastic and the plunger or the stopper is
simply made of plastic, such as a chlorobutyl or bromobutyl polymer, without
particular lamination. Standard glass or plastic syringes are sold, for example, by
Becton-Dickinson; Gerresheimer AG, Schott AG, Germany ; Nuova Ompi srl, Italy ;
and West Pharma/Daykio. In order to facilitate sliding, the plunger or stopper may
have been immersed in a silicone-in-water emulsion so that a silicone film is formed
at its surface. Standard plungers/stoppers are sold by Helvoet, Stelmi and West
Pharma, for example; some of them already being sold coated with a silicone film
(ref. B2 from West Pharma).
Whatever the container used for storage and the device used for closing the
container, administration at the time of injection consists of using a syringe and
sliding the plunger or the stopper/plunger combination so that the vaccine is
delivered.
SUMMARY OF THE INVENTION
We have now found that the material of the container itself as well as that of the
device for closing the container can affect the adsorption rate.
We observed that a vaccine composition containing the hepatitis B surface antigen
(HBsAg) adjuvanted with an aluminum adjuvant and loaded as a single dose in
standard syringe closed with a standard stopper underwent different adsorption rates
when stored under identical conditions and for the same period of time (a few days to
several months) depending on whether the syringe was stored in the vertical or
horizontal position. The same phenomenon has also been seen with vials. The
practical consequence of the different storage positions was that the vaccine
contained in the reservoirs stored vertically was not in contact with the stopper,
whereas there was contact between the composition and the stopper in the
horizontally stored reservoirs.
After a certain period of time, the level of adsorption of HBsAg was measured, and
we observed that the level of adsorption was much lower for the HBsAg contained in
the horizontally-stored reservoirs. This indicated to us that the material of the
standard stopper (chlorobutyl or bromobutyl polymer) was responsible for the
adsorption decrease.
The solution to this problem is either to prevent contact between the adjuvanted
vaccine composition and a stopper made of a material that contributes to decreased
adsorption or to use a stopper made of a material that does not contribute to
decreased adsorption. In one embodiment, the invention comprises a method and
apparatus using a stopper coated with a film of a fluoropolymer, such as Teflon™ or
a Teflon™ - like substance (such as Omniflex™ from Helvoet Pharma or Fluorotec
™ from West Pharma), which decrease or eliminate desorption caused by the
stopper.
DETAILED DESCRIPTION OF THE INVENTION
In one aspect, the invention comprises a first method for reducing and/or slowing
down the desorption of an antigen initially adsorbed on an aluminum adjuvant during
storage, the method comprising (i) loading a container with a vaccine composition
containing the antigen initially adsorbed on the aluminum adjuvant; and (ii) closing
the container with a device acting as a stopper, the surface of the device contactable
with the composition being coated with a fluoropolymer.
In other words, the invention relates to a first method for filling and storing a
composition containing the antigen adsorbed on the aluminum adjuvant which
comprises (i) filling a container with the vaccine composition; and (ii) closing the
container with a device acting as a stopper, the surface of the device contactable with
the composition being coated with a fluoropolymer.
In a similar manner, the invention also relates to the use of a device acting as a
stopper for closing a container containing a vaccine composition comprising the
antigen adsorbed on an aluminum adjuvant, the surface of the device contactable
with the composition being coated with a fluoropolymer.
The container may be, for example, a vial or the reservoir of a syringe. This also
applies to all the other aspects of the invention described hereinafter.
The vaccine composition may be liquid or solid, e.g. lyophilized. A lyophilized
composition may have the appearance of a powder. At the time of injection to a
patient, the lyophilized composition is reconstituted with an appropriate
pharmaceutical solution. This also applies to all the other aspects of the invention
described hereinafter.
According to conventional practice in the art and for the purposes herein, it is
understood that "antigen adsorbed" or "initially adsorbed" is not intended to mean
that 100 % of the antigen amount is actually adsorbed. These terms simply mean that
a substantial amount of antigen is adsorbed. This also applies to all the other aspects
of the invention described hereinafter.
As mentioned above, the device may be a plastic device made out of, for example, a
chlorobutyl or bromobutyl polymer. This standard device is treated with a
fluoropolymer; in particular, it may be submitted to a laminar flow treatment with a
fluoropolymer, this laminar flow treatment being carried out on the entire device or,
at the very least, on the surface of the device contactable with the composition. The
laminar flow treatment makes it possible to deposit a very thin layer (e.g., film) of
the fluoropolymer. As will be appreciated, the area of the coated surface may exceed
the surface contactable with the composition. Indeed, in one embodiment, the whole
surface of the device is coated with the fluoropolymer.
For use in the present invention, the fluoropolymer may be, for example,
polytetrafluoroethylene (PTFE), polytetrafluoropropylene (PTFP), fluorinated
ethylene propylene (FEP, a copolymer of hexafluoropropylene and
tetrafluoroethylene), polychlorotrifluoroethylene (PCTFE), perfluoroalkoxy co
polymer (PFA), poly(ethylene-co-tetrafluoroethylene) (ETFE),
poly(ethylenechlorotrifluoroethylene) (ECTFE), polyvinyl fluoride (PVF) or
polyvinylidene fluoride (PVPF).
The method/use disclosed herein makes it possible to reduce the desorption speed of
the antigen adsorbed on the aluminum adjuvant and/or the desorption percentage (or
desorption rate) after a defined storage time at a given temperature. The desorption
rate may be expressed as follows: (amount of non-adsorbed antigen) / (total antigen
amount present in the composition). Typically, the desorption rate can be assessed by
centrifuging the vaccine composition (samples at T (time) = 0 and at the end of the
experiment); recovering the supernatants which contain the desorbed antigen; and
then quantifying the desorbed fraction by assaying the antigen in the supernatants
and in the whole vaccine using a suitable method chosen according to the nature of
the antigen. The desorption percentage (or desorption rate) can vary from one antigen
to another according to the strength/weakness of the antigen-adjuvant interaction.
Nevertheless, it is considered that the desorption percentage (or desorption rate) can
be reduced by 10 to 15 or 20 % compared with a standard loading method using
standard stoppers - said reduction being measured 1 or 2 months after the date of
loading. During this period of time, the storage is carried out at a temperature of + 5
to 25°C. As may be easily appreciated, the adsorption percentage (adsorption rate)
may be easily deduced from the desorption percentage (or desorption rate).
When the device is used not only to close the container but also to deliver the
composition contained in the container, such as by sliding the plunger of a syringe, it
is recommended to siliconize the inner surface of the container.
However, it has been observed that silicone may in some cases be detrimental to
adsorption. Indeed, the desorption rate observed in compositions stored in syringes
conventionally siliconized by mere surface-treatment with a silicone-in-water
emulsion may be higher than the desorption rate observed in compositions stored in
non-siliconized containers. We postulate that although the silicone adheres to the
inner surface of the container, it remains in free form and, upon shaking or stirring,
can flow away from the inner surface and pass into the container's content (the
vaccine composition).
We have now found that this latter problem can be solved by using a container
wherein the inner surfaces are coated with polymerized silicone. Such a container
can be obtained by treating the inner surface of the container with a silicone-in-water
emulsion, followed by heating the container, for example at a temperature of 270 to
330°C for 30 min. Upon heating, the silicone polymerizes on the inner surface of the
container and is therefore no longer capable of mixing with the composition.
Polymerizing the silicone makes it possible to reduce the surface energy of the
silicone to which the vaccine composition may be sensitive.
Additionally, the siliconizing operation comprising a polymerization step (i) is more
precise and more homogeneous that a simple standard siliconizing operation; and (ii)
makes it possible to reduce the amount of silicone that is used (that is, loaded on the
inner surface of the container) by about a factor of 10 without any loss of lubricating
effect. For example, according to a standard siliconizing process, from 400 to 1000
g of silicone are deposited in a syringe intended to contain doses of 0.5-1 ml (the
total inner surface of the 0.5-1 ml syringe reservoir is about 8 cm2; in this example
this surface corresponds to an amount of silicone of from about 50 to 125 g / cm2),
whereas from 40 to 100 g of silicone are sufficient for the same syringe (about 5 to
12 g / cm2) if silicone is deposited on the inner surfaces of the container and then
polymerized, for example by heating. The fact that the inner surface of the syringe is
coated with a low amount of polymerized silicone in a more homogenous manner
than with a low amount of free silicone allows non-siliconized plungers to slide
smoothly, whereas such plungers are inoperative with syringes coated with low
amount of free silicone.
This is the reason why the invention also comprises a second method for reducing
and/or slowing down the desorption of an antigen adsorbed on an aluminum
adjuvant, the method comprising filling a container with a vaccine composition
comprising the antigen adsorbed on the aluminum adjuvant, wherein the inner
surface of the container is coated with polymerized silicone.
In other words, the invention also comprises a second method for loading and storing
a vaccine composition containing an antigen adsorbed on the aluminum adjuvant, the
method comprising filling a container with the composition wherein the inner surface
of the container is coated with polymerized silicone.
In a similar manner, the invention also comprises the use of a container having an
inner surface coated with polymerized silicone for storing a vaccine composition
comprising an antigen adsorbed on an aluminum adjuvant.
Advantageously, the container having inner surfaces coated with polymerized
silicone is made of plastic or glass. Advantageously, the container is the reservoir of
a syringe.
The amount of polymerized silicone coated on the inner surface of the container is
from 3 to 25 g / cm2 ; advantageously from 5 to 20 g / cm2 ; preferably from 5 to
15 g / cm2.
As may be easily understood, the container used in the first methods of the invention
may be advantageously coated with polymerized silicone as described above.
In another aspect, the invention comprises:
A - A container (i) which contains a vaccine composition comprising an antigen
adsorbed on an aluminum adjuvant ; and (ii) which is closed by a device
acting as a stopper, wherein the surface of the device contactable with the
composition is coated with a fluoropolymer;
B - A container (i) having inner surfaces coated with polymerized silicone ; and
(ii) containing a vaccine composition comprising an antigen adsorbed on an
aluminum adjuvant ; and
C - A container (i) having inner surfaces coated with polymerized silicone ; (ii)
containing a vaccine composition comprising an antigen adsorbed on an
aluminum adjuvant ; and (iii) which is closed by a device acting as a stopper,
wherein the surface of the device contactable with the composition is coated
with a fluoropolymer.
In other words, the invention relates to a vaccine composition comprising an antigen
adsorbed on an aluminum adjuvant which is loaded into and stored in a container (i)
having the inner surface coated with polymerized silicone; and/or (ii) which is closed
by a device acting as a stopper, wherein at least the surface of the device contactable
with the composition is coated with a fluoropolymer.
Vaccine compositions stored in containers according to the invention include :
A vaccine composition comprising an antigen, wherein the minimal antigen
amount required for intended use (e.g., as a dose for administration to a human) is
adsorbed on an aluminum adjuvant ;
A vaccine composition comprising an antigen adsorbed on an aluminum
adjuvant, wherein the vaccine composition when loaded in a container for use in the
present invention, exhibits an adsorption percentage of at least :
(a) 65-70 % of the total antigen amount present in the composition, when,
immediately after loading, the composition is stored at (i) 5 + 3°C for 2-3 years ; or
(ii) 25 + 3°C for 2-3 months ; or
(b) 80-90 %, of the total antigen amount present in the composition, when,
immediately after loading, the composition is stored at 5 + 3°C for 18 months; and
A vaccine composition comprising an aluminum adjuvant and an antigen able
to adsorb onto the aluminum adjuvant, wherein the percentage of the antigen
adsorbed on the aluminum adjuvant is at least 5 or 10 % higher than the percentage
observed when the same vaccine composition is contained in a standard container
having uncoated inner surfaces or inner surfaces coated with non-polymerized
silicone, the comparison between the antigen adsorption percentages being carried
out after storage of the vaccine-containing containers at 25°C for 2 months, starting
from the date of filling the containers.
For the purposes of the present invention, the container may be any type of reservoir,
such as vials or syringes, and may contain multiple doses (multidose container) or a
single dose (single-dose container). As an example, the container may be a syringe or
a part of a syringe comprising the reservoir containing the vaccine closed by a device
acting as a stopper and as a system for releasing the vaccine at the time of
administration (e.g., using a plunger). The device acting as a stopper may be a
plunger.
Stoppers and/or plungers for use in the present invention are sold, for example, by
Helvoet Pharma (Omniflex™ technology) and by West Pharma (Fluorotec™
technology). Glass syringe reservoirs coated with polymerized silicone for use in the
present invention are sold, for example, by Nuova Ompi srl, Becton-Dickinson and
Gerresheimer (Baked-on technology).
The antigen and the aluminum adjuvant may be any antigen and any aluminum
adjuvant provided, of course, that they are both capable of interacting with each
other. Furthermore, it may easily be understood that the present invention is of
particular interest for an antigen-aluminum adjuvant pair having a relatively weak
interaction force ; the interaction force possibly depending on the environment. This
interaction force can be assessed according to a variety of tests. For example, an
aluminum adjuvant may be used to form various antigen-adjuvant pairs (the antigen
varies from one pair to the other, the adjuvant remaining the same). Then a large
amount of a compound able to compete with the antigen for the interaction with the
adjuvant is added. The various preparations are centrifuged and the supernatants
recovered. Finally, the amount of antigen desorbed is assayed in the supernatants,
and as a result, antigens may be compared for their interaction force with the
adjuvant.
A relatively weak interaction force is an interaction force that leads to an adsorption
that may be detrimentally affected by a standard filling with the composition
containing the antigen-aluminum adjuvant complex. Various elements involved in
the manufacture of a container, such as, for example, latex, antioxidants, silicone and
metal ions (e.g., zinc and tungsten), can destabilize the antigen-adjuvant complex.
By "adsorption" it is generally meant any phenomenon aimed at forming an antigenadjuvant
complex involving i.a. electrostatic interaction forces, hydrophobic
interactions or ligand exchange. Thus, the antigen may be attached at the surface of
the network of the aluminum adjuvant or embedded inside after co-precipitation with
the aluminum adjuvant.
For use in the present invention, an aluminum adjuvant may be aluminum oxy
hydroxide (AIOOH), such as the product sold by Brenntag AG (Superfos) or Reheis
Corp. ; and aluminum hydroxy phosphate (AIOFIPO4), such as the product sold by
Alphos.
For a vaccine composition to be effective, the minimal antigen amount required for
adsorption onto the aluminum adjuvant essentially depends upon the antigen itself,
and is readily determinable by those of ordinary skill in the art.
In a particular embodiment, the antigen can be the hepatitis B surface antigen
(FIBsAg). It is particularly advantageous to adsorb HBsAg onto AIOOH as HBsAg
exhibits an iso electric point (TEP) less than 7 (about 4 to 5) and AIOOH exhibits a
point of zero charge (PZC) greater than 7 (about 9 to 11).
The vaccine composition for use in the present invention can contain one or more
antigen(s), at least one of them being adsorbed on the aluminum adjuvant and it
being possible for the others to be adsorbed as well or not.
According to one embodiment, the composition for use in the present invention
comprises HBsAg adsorbed on AIOOH (AIOOH - HbsAg complex) and a second
antigen, which is polyribosylribitol phosphate (PRP) of Haemophilus influenzae
(HiB valence), preferably in a form conjugated to a carrier protein (C) which may be
i.a. Dt or Tt.
According to another particular embodiment, when the antigen adsorbed on the
aluminum adjuvant is HBsAg, the vaccine composition may also contain, as
additional antigens, one or more of the following : diphtheria toxoid (Dt) (diphtheria
valence) ; tetanus toxoid (Tt) (tetanus valence) ; Bordetella pertussis detoxified toxin
(Ptdx), fimbriae, filamentous haemagglutinin (FHA) and/or pertactin (69 kD antigen)
{pertussis valence) ; inactivated poliovirus serotype 1, 2, or 3 (polio valence) ; and
polyribosylribitol phosphate (PRP) of Haemophilus influenzae (HiB valence),
preferably in a form conjugated to a carrier protein (C) which may be i.a. Dt or Tt.
As a matter of example, the composition may comprise HBsAg, Dt, Tt, Pt and FHA
adsorbed on AIOOH (the AIOOH - HbsAg-Dt-Tt-Pt-FH A complex), the polio
valence, and PRP-C substantially non-adsorbed on AIOOH.
In a general manner, the invention is also particularly advantageous when the vaccine
composition comprises several valences, for example 2, 3, 4, 5, 6 or more, each
represented by one or more antigens (2, 3, 4 or 5), several antigens being adsorbed
on the aluminum adjuvant. Indeed, under the standard filling mode, the higher the
number of antigens/valences adsorbed on the aluminum adjuvant, the more critical is
the phenomenon of destabilization by the container. The antigen-adjuvant interaction
force often differs from one antigen to another and, in a composition containing
several antigens, the antigen with the weakest interaction force exhibits the highest
tendency to desorb under adverse conditions.
Examples and experimental results
A - A bulk of a vaccine composition containing the hepatitis B surface antigen,
diphtheria toxoid, tetanus toxoid, and pertussis valence, each adsorbed on aluminum
oxy hydroxyde, as well as the polio and non-adsorbed Haemophilus influenzae B
(HiB) valences was distributed into three categories of single-dose syringes, the
characteristics of which were as follows :
(1) standard siliconized glass syringes with standard stopper/plunger made of
non-laminated plastic ;
(2) standard siliconized glass syringes with fluoropolymer-coated
stopper/plunger (West Pharma ; Fluorotech™ technology) ; and
(3) syringes, the inner surface of which is coated with polymerized silicone
(Baked-on syringe system Luercone™ from Gerresheimer) with
fluoropolymer-coated stopper/plunger (West Pharma; Fluorotech™
technology).
The bulk was distributed in 0.5 mL single doses, each dose containing 10 g of
HBsAg, 30 Lf of Dt, 10 Lf of Tt, 25 g of Pt, 25 g of FHA, 40 DU (Antigen D
Unit) of IPVl, 8 DU of IPV2, 32 DU of IPV3, 12 g of PRP (in PRP-Tt conjugate
form), 0.6 mg of Al, 55 mM of phosphate ions, 20 mM of carbonate ions, and Tris
sucrose buffer, 2.5 mM, 2.125 %, at pH 6.8-7.2.
All the syringes of the three categories were stored horizontally at 25°C for two
months (accelerated ageing). The HBsAg desorption was measured in each of the
three categories at T = 0 (just after loading the syringes) and then after two months.
Desorption was evaluated by centrifuging the content of the syringes and then
measuring the amount of desorbed HBsAg present in the supernatant by ELISA
(sandwich ELISA, involving a mouse anti-HBsAg monoclonal antibody (IgM) for
coating and capture, a second mouse anti-HBsAg monoclonal antibody (IgG) and a
third anti-mouse IgG polyclonal antibody coupled to peroxydase (Sigma, Ref.
A3673) which is revealed by adding tetramethyl benzidine).
At T (time) = 0, the HbsAg adsorption level was identical in the three categories (98
% of the total HBsAg was adsorbed). At T = 2 months, desorption was observed in
all the categories, but the desorption percentage differed depending upon the
category. The highest desorption percentage was found in category (1) (At T = 1 and
2 months, 55 and 50 % of the total HBsAg was adsorbed, respectively), whereas the
lowest percentage was found in category (3) (At T = 1 and 2 months, 72 and 69 % of
the total HBsAg was adsorbed, respectively).
B - A bulk of the vaccine composition described in A - was distributed into two
categories of single-dose 1mL syringes, the characteristics of which were as follows:
(1) standard siliconized glass syringes (free silicone); and
(2) non-siliconized syringes.
The bulk was distributed in 0.5 mL single doses, each dose containing 10 g of
HBsAg, 30 Lf of Dt, 10 Lf of Tt, 25 g of Pt, 25 g of FHA, 40 DU (Antigen D
Unit) of IPVl, 8 DU of IPV2, 32 DU of IPV3, 12 g of PRP (in PRP-Tt conjugate
form), 0.6 mg of Al, 55 mM of phosphate ions, 20 mM of carbonate ions, and Tris
sucrose buffer, 2.5 mM, 2.125 %, at pH 6.8-7.2.
All the syringes of the two categories were stored vertically at 25°C for two months
(accelerated ageing). The HBsAg desorption was measured in each of the two
categories at T = 0 (just after filling syringes) and then after two months, as
described in A - above.
At T (time) = 0, the HbsAg adsorption level was identical in the two categories (98
% of the total HBsAg was adsorbed). At T = 2 months, desorption was observed in
all the categories, but the desorption percentage differed depending upon the
category. The highest desorption percentage was found in category (1) (At T = 1 and
2 months, 69 and 68 % of the total HBsAg was adsorbed, respectively), whereas the
lowest desorption percentage was found in category (2) (At T = 1 and 2 months, 73
% of the total HBsAg was adsorbed). This clearly indicates that the antigen
adsorption onto an aluminum adjuvant is sensitive to free silicone.
C - A bulk of the vaccine composition described in A - was distributed into three
types of single-dose 1mL syringes, the characteristics of which were as follows:
(1) low siliconized glass syringes (50-100 g free silicone / syringe);
(2) standard highly siliconized glass syringes ((RTF syringe Luercone™
from Gerresheimer) : 800 g to lmg free silicone /syringe) ; and
(3) syringes having inner surface coated with polymerized silicone (50-100
g / syringe).
Syringes of category (1) are operative only if the plunger used for injection is also
siliconized, because the amount of silicone coating the inner surface of the syringe is
too low to allow sliding on its own.
All the syringes (types 1 to 3) were closed with the same type of non-siliconized
stopper.
The bulk vaccine was distributed in 0.5 mL single doses, each dose being as
described in A and B.
All the syringes of the three types were stored vertically at 25°C for two months
(accelerated ageing). The HBsAg desorption was measured in each of the three types
at T = 0 (just after filling syringes) and then after two months, as described in A -
above.
At T (time) = 0, the HbsAg adsorption level was identical in the three types (94 % of
the total HBsAg was adsorbed). At T = 2 months, desorption was observed in all
syringes, but the desorption percentage differed depending upon the type. The
highest desorption percentage was found in type (2) (At T = 1 and 2 months, 60 and
58 % of the total HBsAg was adsorbed, respectively), whereas the desorption
percentage was found similar in types (1) and (3) and definitively much lower than in
type (2): In type (1), at T = 1 and 2 months, 73 % and 68 % of the total HBsAg was
adsorbed, respectively. In type (3), at T = 1 and 2 months, 69 % and 66 % of the total
HBsAg was adsorbed, respectively.
Again, this clearly indicates that (i) the antigen adsorption onto an aluminum
adjuvant is sensitive to free silicone loaded in an amount necessary for sliding and
(ii) polymerization of silicone allows overcoming this issue.
D - A stability study has been conducted at 5 + 3°C for 18 months with the filled
syringes described in A - (3). At least 80-90 % of the total HBsAg was still adsorbed
at the end of the 18-month period.
What is claimed
A method for storing a vaccine composition containing an antigen adsorbed
on an aluminum adjuvant, the method comprising (i) loading the composition
into a container and (ii) closing the container with a device acting as a
stopper, wherein the surface of the device contactable with the composition is
coated with a fluoropolymer.
The method as claimed in claim 1, wherein the vaccine composition is in
liquid or lyophilized form.
The method as claimed in claim 1 or 2, wherein the fluoropolymer is selected
from the group consisting of polytetrafluoroethylene (PTFE),
polytetrafluoropropylene (PTFP), fluorinated ethylene propylene (FEP, a
copolymer of hexafluoropropylene and tetrafluoroethylene),
polychlorotrifluoroethylene (PCTFE), perfluoroalkoxy co-polymer (PFA),
poly(ethylene-co-tetrafluoroethylene) (ETFE),
poly(ethylenechlorotrifluoroethylene) (ECTFE), polyvinyl fluoride (PVF)
and polyvinylidene fluoride (PVPF).
The method as claimed in claim 1, 2 or 3, wherein the container is the
reservoir of a syringe and the device acting as a stopper is a plunger.
The method as claimed in anyone of claims 1 to 4, wherein the inner surface
of the container is coated with polymerized silicone.
A method for and storing a vaccine composition containing an antigen
adsorbed on an aluminum adjuvant, the method comprising loading the
composition into a container wherein the inner surface of the container is
coated with polymerized silicone.
The method as claimed in claim 6, wherein the vaccine composition is in
liquid or lyophilized form.
The method as claimed in anyone of claims 1 to 7, wherein the antigen
contained in the composition is hepatitis B surface antigen and the aluminum
adjuvant is aluminum oxy hydroxide.
9 . A container for storing and/or administering a vaccine composition, wherein
the container (i) contains a vaccine composition comprising an antigen
adsorbed on an aluminum adjuvant and (ii) is closed by a device acting as a
stopper, wherein the surface of the device contactable with the composition is
coated with a fluoropolymer.
10. The container as claimed in claim 9, wherein the vaccine composition^ in
liquid or lyophilized form.
11. The container as claimed in claim 9 or 10, wherein the fluoropolymer is
selected from the group consisting of polytetrafluoroethylene (PTFE),
polytetrafluoropropylene (PTFP), fluorinated ethylene propylene (FEP, a
copolymer of hexafluoropropylene and tetrafluoroethylene),
polychlorotrifluoroethylene (PCTFE), perfluoroalkoxy co-polymer (PFA),
poly(ethylene-co-tetrafluoroethylene) (ETFE),
poly(ethylenechlorotrifluoroethylene) (ECTFE), polyvinyl fluoride (PVF)
and polyvinylidene fluoride (PVPF).
12. A container for storing and/or administering a vaccine composition, wherein
the container (i) has inner surfaces coated with polymerized silicone and (ii)
contains a vaccine composition comprising an antigen adsorbed on an
aluminum adjuvant.
13. The container as claimed in claim 12, wherein the vaccine composition is in
liquid or lyophilized form.
14. A container for storing and/or administering a vaccine composition, wherein
the container (i) has inner surfaces coated with polymerized silicone; (ii)
contains a vaccine composition comprising an antigen adsorbed on an
aluminum adjuvant; and (iii) which is closed by a device acting as a stopper,
wherein the surface of the device contactable with the composition is coated
with a fluoropolymer.
15. The container as claimed in claim 14, wherein the vaccine composition, is in
liquid or lyophilized form.
16. The container as claimed in claim 14 or 15, wherein the fluoropolymer is
selected from the group consisting of polytetrafluoroethylene (PTFE),
polytetrafluoropropylene (PTFP), fluorinated ethylene propylene (FEP, a
copolymer of hexafluoropropylene and tetrafluoroethylene),
polychlorotrifluoroethylene (PCTFE), perfluoroalkoxy co-polymer (PFA),
poly(ethylene-co-tetrafluoroethylene) (ETFE),
poly(ethylenechlorotrifluoroethylene) (ECTFE), polyvinyl fluoride (PVF)
and polyvinylidene fluoride (PVPF).
17. The container as claimed in anyone of claims 12 to 16, wherein the container
is the reservoir of a syringe that is closed by a plunger.
18. The container as claimed in anyone of claims 9 to 17, wherein the antigen
contained in the composition is hepatitis B surface antigen and the aluminum
adjuvant is aluminum oxy hydroxide.