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Technology transfer and scale-up of the Flublok® recombinant hemagglutinin (HA) influenza vaccine manufacturing process

Identifieur interne : 001008 ( Main/Exploration ); précédent : 001007; suivant : 001009

Technology transfer and scale-up of the Flublok® recombinant hemagglutinin (HA) influenza vaccine manufacturing process

Auteurs : Barry Buckland [États-Unis, Royaume-Uni] ; Robert Boulanger [États-Unis] ; Mireli Fino [États-Unis] ; Indresh Srivastava [États-Unis] ; Kathy Holtz [États-Unis] ; Nikolai Khramtsov [États-Unis] ; Clifton Mcpherson [États-Unis] ; Jamal Meghrous [États-Unis] ; Paul Kubera [États-Unis] ; Manon M. J. Cox [États-Unis]

Source :

RBID : Pascal:14-0246271

Descripteurs français

English descriptors

Abstract

Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650 L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok®). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10 L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100 L, 650 L and 2500 L scale. An illustration is given of how the technology was transferred from the benchmark 650 L scale facility to a retrofitted microbial facility at the 2500 L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok® process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture.


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Le document en format XML

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<div type="abstract" xml:lang="en">Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650 L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok®). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10 L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100 L, 650 L and 2500 L scale. An illustration is given of how the technology was transferred from the benchmark 650 L scale facility to a retrofitted microbial facility at the 2500 L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok® process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture.</div>
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</settlement>
<orgName>
<li>University College de Londres</li>
</orgName>
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<country name="États-Unis">
<region name="Connecticut">
<name sortKey="Buckland, Barry" sort="Buckland, Barry" uniqKey="Buckland B" first="Barry" last="Buckland">Barry Buckland</name>
</region>
<name sortKey="Boulanger, Robert" sort="Boulanger, Robert" uniqKey="Boulanger R" first="Robert" last="Boulanger">Robert Boulanger</name>
<name sortKey="Cox, Manon M J" sort="Cox, Manon M J" uniqKey="Cox M" first="Manon M. J." last="Cox">Manon M. J. Cox</name>
<name sortKey="Fino, Mireli" sort="Fino, Mireli" uniqKey="Fino M" first="Mireli" last="Fino">Mireli Fino</name>
<name sortKey="Holtz, Kathy" sort="Holtz, Kathy" uniqKey="Holtz K" first="Kathy" last="Holtz">Kathy Holtz</name>
<name sortKey="Khramtsov, Nikolai" sort="Khramtsov, Nikolai" uniqKey="Khramtsov N" first="Nikolai" last="Khramtsov">Nikolai Khramtsov</name>
<name sortKey="Kubera, Paul" sort="Kubera, Paul" uniqKey="Kubera P" first="Paul" last="Kubera">Paul Kubera</name>
<name sortKey="Mcpherson, Clifton" sort="Mcpherson, Clifton" uniqKey="Mcpherson C" first="Clifton" last="Mcpherson">Clifton Mcpherson</name>
<name sortKey="Meghrous, Jamal" sort="Meghrous, Jamal" uniqKey="Meghrous J" first="Jamal" last="Meghrous">Jamal Meghrous</name>
<name sortKey="Srivastava, Indresh" sort="Srivastava, Indresh" uniqKey="Srivastava I" first="Indresh" last="Srivastava">Indresh Srivastava</name>
</country>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Buckland, Barry" sort="Buckland, Barry" uniqKey="Buckland B" first="Barry" last="Buckland">Barry Buckland</name>
</region>
</country>
</tree>
</affiliations>
</record>

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