EU approves Novartis's 'mock-up' pandemic vaccine

[Treyfish]

EU approves Novartis's 'mock-up' pandemic vaccine

Robert Roos News Editor

May 9, 2007 (CIDRAP News) ? The European Union (EU) this week approved a "mock-up" influenza vaccine made by Novartis to permit a faster start on vaccine production in the event of a flu pandemic.
When the World Health Organization (WHO) declares a flu pandemic, the vaccine, called Focetria, will be adapted to contain the pandemic virus, the Swiss-based drug company announced yesterday. The vaccine will not be manufactured until a pandemic is declared.
The European Medicines Agency's (EMEA's) Committee for Medicinal Products for Human Use (CHMP) recommended approval of Focetria on Feb 22. A CHMP statement on that date said the vaccine was based on a 2004 strain of H5N1 avian flu from Vietnam.
The vaccine contains Novartis's proprietary adjuvant MF59, an immune-boosting chemical, which can reduce the amount of active ingredient needed in each dose, the company says. The dose used in the approved mock-up vaccine is 15 micrograms (mcg), according to the CHMP.
"Once the WHO declares a pandemic, Novartis will submit a revised application to the European Medicines Agency to incorporate the identified viral strain," Novartis officials said in a news release yesterday. "The Focetria mock-up file submitted for EU approval in early 2006 was based on clinical studies involving the MF59 adjuvant and different influenza strains with pandemic potential, including H5N1 and H9N2."
A CHMP statement from December 2006 defines a mock-up vaccine as one "that mimics the future pandemic influenza vaccine in terms of its composition and manufacturing method" but contains a different flu strain.
Novartis said it is also seeking EU approval for a prepandemic H5N1 vaccine that includes MF59 and is based on the same technology as Focetria. The vaccine is intended for use before a pandemic declaration to help "prime" the immune system to fight off H5N1 infections, the company says.
Both Focetria and the prepandemic vaccine involve the conventional production method of growing the vaccine virus in eggs, according to Eric Althoff, a Novartis spokesman in Emeryville, Calif.
Once a pandemic flu strain is identified, it will take at least 6 months to adapt the virus for production in eggs and start producing the vaccine in quantity, Althoff told CIDRAP News yesterday.
"It'll be at least 6 months, just from the simple time of getting enough raw material, ie, eggs, to have full-scale production," he said.
On Apr 26 the CHMP recommended EU approval of a Novartis seasonal flu vaccine grown in cell culture instead of in eggs. Althoff said the company also aims to make a cell culture?based pandemic flu vaccine, but development is in an early stage.
Cell-culture production is described as somewhat faster and much more flexible than egg-based production. No cell-based flu vaccine has been marketed anywhere as yet, though the EU in 2001 approved a cell-based seasonal flu vaccine made by Solvay Pharmaceuticals for sale in the Netherlands.
Althoff said Novartis is talking with US regulators about how to seek approval for both pandemic mock-up and prepandemic vaccines. European authorities provided guidance earlier than the US Food and Drug Administration (FDA) did on the steps needed to get approval for a mock-up vaccine, he said.
"That pathway hadn't been mapped out by the FDA or how to handle the review and approval of such a vaccine," he said. But an FDA advisory committee recently prescribed the necessary steps, he added. "I think there's great progress now and more clarity about how to move forward."
In April the FDA approved an H5N1 vaccine made by Sanofi Pasteur, despite only modest immunogenicity demonstrated in clinical trials. The Department of Health and Human Services has been stockpiling the vaccine for use in a pandemic. http://www.cidrap.umn.edu/cidrap/con...7novartis.html

[gsgs]

Re: EU approves Novartis's 'mock-up' pandemic vaccine

> It'll be at least 6 months, just from the simple time
> of getting enough raw material, ie, eggs, to have
> full-scale production

12 weeks according to:

http://www.emea.europa.eu/pdfs/general/direct/pr/50155706en.pdf

22 weeks, I had read last year at www.pei.de


here is a link (in German)

http://www.pei.de/cln_042/nn_434236...pfstoff/06.html

it basically says, that in worst case they need:
edit:[10 weeks for producing the seedvirus]
12 weeks for preparation
10 weeks for producing the first 80 million doses
10 weeks for producing the 2nd 80 million doses


in the best case, using a prepared "seed virus" (which they don't have yet, as I understand)
they need :
10 weeks for preparation
6 weeks for producing the 1st 80 million doses
6 weeks for producing another 80 million doses for the 2nd required shot.
They would start delivering the first doses after 10 months.edit:[weeks,not nonths]
(But don't know yet, who would get them with what priority and won't tell you in advance,
where in that priority chain you are...)


and, as I read elsewhere, one dose would cost approximately 5 Euros($7)

[Treyfish]

Re: EU approves Novartis's 'mock-up' pandemic vaccine

Thanks, GSGS!I'm betting it will take a lot longer to filter down to the ole general public. A good reason to stay informed and adequately prepared.

[DRJJ]

Re: EU approves Novartis's 'mock-up' pandemic vaccine

This is wildy optimistic, according to my understanding. The current vaccine requires 3 fertilized eggs, one to grow each strain of the virus. These three eggs will make 3 doses of the combined three strains: 9 eggs to make 3 doses, each with 3 strains of the virus. And, currently, the eggs are grown from specially managed hens who lay their eggs at limited times of the year. Then the eggs have to be "managed" in special manufacturing plants while the virus grows in the eggs. Also, the losses in manufacturing are especially high, given that the H5N1 virus may be/has been lethal to the fertilized eggs. Add to this the expectation that at least 2 doses will likely be required to provide immunity and the math is horrendous.

100,000,000 double doses of a trivalent vaccine requires 600,000,000 fertilized, sterile eggs.

This entire vaccine manufacturing system is so fragile and difficult to ramp up, especially in an emergency when chickens are dying and humans are frightened of catching fatal chicken-borne diseases.

Imagine an ill human worker, infecting the sterile chicken population and, thereby, jeopardizing the vaccine manufacturing.

The existing vaccine manufacturing facilities are likely to disintegrate under the stress of a pandemic.

[Gert van der Hoek]

Re: EU approves Novartis's 'mock-up' pandemic vaccine

press release Novartis on a pre-pandemic vaccine

2008.09.19

Novartis MF59?-adjuvanted vaccine rapidly induces protective antibody levels against diverse strains of avian flu

Study shows the investigational pre-pandemic vaccine AFLUNOV? provides rapid immune response in individuals primed with MF59-adjuvanted H5 vaccine up to six years earlier[1]

Individuals primed with MF59 adjuvant developed immunity seven days after receiving the AFLUNOV booster

Study supports notion of pre-pandemic vaccination to ensure protective antibody levels in population with one additional immunization in the event of a pandemic

Basel, September 19, 2008 - A new study shows that individuals immunized six years earlier with an MF59 adjuvanted H5N3 (clade 0) vaccine mounted a protective immune response seven days after a single immunization with an H5N1 (clade 1) vaccine containing the Novartis proprietary adjuvant MF59.

The immune response was broadly cross reactive and covered all H5N1 clades known to date. These data were presented at the Third European Influenza Conference in Vilamoura, Portugal.

Responses were seen even against viral strains not included in either vaccine[1] suggesting proactive priming strategies with an MF59 adjuvanted-H5 vaccine may have the potential to help save lives in an avian influenza pandemic situation.

"These data highlight the potential for priming the public against an avian influenza of pandemic proportion with the MF59 adjuvant. The results indicate that regardless of which avian strain individuals are originally primed with, they are quickly protected against a broad range of avian strains following their MF59-adjuvanted booster vaccine, even strains they were not initially inoculated against," said study investigator Iain Stephenson M.R.C.P., Infectious Diseases Unit, University Hospitals Leicester and Department of Inflammation, Infection and Immunity, University of Leicester, UK.

"These results potentially provide a rationale to prevent pandemic influenza by proactively immunizing the public with stockpiled pre-pandemic vaccines containing MF59," Dr Stephenson added.

According to the trial results, healthy adults primed with an MF59-adjuvanted H5 vaccine at least 6 years ago, and boosted with the Novartis pre-pandemic vaccine AFLUNOV (7.5microgram MF59-adjuvanted A/Vietnam/1194/2004 clade 1 H5N1), showed a protective cross-reacting antibody response to diverse H5N1 virus variants. Response was seen within 7 days and results were significantly higher (P< 0.05) at 14 days than those primed with a un-adjuvanted vaccine[1]. In addition, these study results suggest primed individuals would only need one dose of an MF59-adjuvanted vaccine in a pandemic situation to elicit initial protection reducing overall response time, and potentially the spread of the virus[1].

"These findings show that priming subjects with the Novartis proprietary adjuvant MF59 included in AFLUNOV can induce long-lasting immune-memory and further supports a proactive priming strategy as part of pandemic preparedness efforts" said Dr. Joerg Reinhardt, CEO of Novartis Vaccines and Diagnostics, a division of Novartis. "Novartis Vaccines is committed to putting forth the most effective vaccine possible to help protect the global public against a possible pandemic situation."

An influenza pandemic occurs when a new influenza strain emerges (one to which humans have no immunity), mutates and spreads globally as a virus. Although it is not possible to predict the actual pandemic influenza strain, global health authorities have identified H5N1 avian influenza as a strain with the greatest pandemic potential in humans[3]. H5N1 is currently circulating in birds and has caused serious illness in more than 380 people worldwide with a mortality rate, among people known to have been infected, of greater than 60 percent[4].

The purpose of pre-pandemic vaccination is to prime the immune system to better defend against infections from an H5N1 influenza virus and is intended for use before the World Health Organization (WHO) declares an influenza pandemic. AFLUNOV is the only pre-pandemic vaccine in development with an extensively-studied adjuvant, MF59, that is supported by more than 10 years of clinical safety data and commercial use.

Study details

In an open-label study, 54 healthy adults (age 23-60 years) received two doses of AFLUNOV (7.5microgram MF59-adjuvanted A/Vietnam/1194/2004 clade 1 H5N1) vaccine 21 days apart. Twenty-four subjects were primed with either MF59-adjuvanted or an un-adjuvanted H5N3 (A/duck/Singapore/1997 clade 0-like) vaccine at least 6 years earlier and 30 subjects were unprimed[1]. Some subjects also received a booster dose, 16 months after primary immunization. Pre and post-vaccination antibody to antigenically diverse H5 viruses were measured by hemagglutination-inhibition (HAI), neutralizing antibody (MN) and single radial hemolysis (SRH).

Among primed subjects, protective cross-reacting antibody titers to diverse H5N1 virus variants were seen by day 7 after a single vaccine dose[1]. In subjects primed with an MF59-adjuvanted vaccine responses were statistically significantly higher (P< 0.05) than those primed with un-adjuvanted vaccine. By day 7, after one dose of AFLUNOV, >=80% of MF59-H5 primed recipients achieved sero-protective HAI titers of >=1:40 to all clade 1, 2.1, 2.2, and 2.3 avian H5 virus variants tested as well as the original antigen. In MF59-H5N3 primed subjects, responses were greatest at day 14 with geometric mean antibody titers of 1:378, 1:1754 and 73mm2 to the clade 1 A/Vietnam/2004 vaccine strain and 1:347, 1:2128 and 72mm2 to a clade 2 A/Turkey/2005 variant by HAI, MN and SRH respectively[1].

- snip -

http://www.huginonline.com/plsql/try/pressreleases.queryview?P_IDENTIFIER=1252754&Z_CHK=32060&p_la=5&p_web=5

[gsgs]

Re: EU approves Novartis's 'mock-up' pandemic vaccine

and Japan and USA do consider to administer the expiring
prepandemic vaccine.

What about Switzerland ?
Maybe they can sell some of their expiring prepandemic vaccine
to privates ??