Vaccine producers’ resources meet pandemic demand

The surge in vaccines against influenza has surprised Governments across the world, with the stark admission that demand was unforeseen. Avian flu, which has emerged as a real threat to humans, has not only have added to the danger but has put vaccine manufacturers under increased pressure to meet the demand.

Concerns over growing cases of avian flu and the possibility of a flu pandemic have led to more people than usual seeking vaccination against seasonal flu, even though this would not protect against a pandemic strain.

News of how the UK government was caught short in the wake of an impending pandemic is surprising, considering the media hype fuelling public concerns about the bird flu pandemic threat.

The UK's Department of Health (DoH) currently meets vaccine manufacturers each year to discuss requirements based on previous demand and other factors, which need to be taken into account.

The understanding was based on 11 million people being at risk, but was recently revised to 13.2 million.

The Department of Health said the 14 million vaccine doses ordered by GPs from manufacturers and held in a contingency pot by government had all been used. The department has ordered 200,000 more doses, but those will not be available until 2006.

Influenza vaccines need to be changed, generally each year, to cope with mutations and this need to change vaccine formulations results in delays when flu breaks out.

Human flu is caused by two influenza strains, A and B. The killer bird flu virus H5N1 is a derivative of the A strain. The pandemic vaccine is being developed to tackle the A strain while the universal vaccine should act against A and B.

Vaccine manufacturers have certainly learnt the lessons of last year, when fingers were pointed at producers such as Roche and GlaxoSmithKline. This year has seen considerable time and effort invested into stepping up production to meet demand. Roche makes Tamiflu and GSK an inhalable drug called Relenza.

Samantha Christey, manager, GSK Biologicals World Wide, told In-PharmaTechnologist.com: "Recently GSK has invested $2 billion to expand the company's flu vaccine manufacturing capacity and to increase the production of its antiviral Relenza (zanamivir for inhalation). Both could help meet public health needs in the case of pandemic."

"The company expects to increase its North American manufacturing capacity with the proposed acquisition of ID Biomedical, a Canadian vaccine manufacturer," she added.

Special preparations to cope with the expected demand include an investment of € 94.3 million to double production capacity for its Influsplit/Fluarix flu vaccine at its Sachsisiches SerumWerk (SSSW) plant in Dresden, Germany.

Christey added: "GSK will build a second plant at the site and increase its annual production capacity from 35 million influenza vaccine doses per year currently, to 60 million doses annually before the end of this decade."

Meanwhile Roche's response to the flu outbreak has resulted in production reaching full capacity. Almost all governments have ordered it, and thus demand may not be satisfied.

Roche had commented that it might allow other companies or governments to make it under licence.

"More than 200 requests from third parties have been received to date and Roche production experts have already been in initial talks with 8 companies, amongst them large generic manufacturers and major pharmaceutical companies, as well as with a number of governments, including Taiwan and Vietnam," the company said.

"The goal is to be in a position to select potential partners for more detailed discussions by the end of November."

The company has also said it hopes to be able to step up its own annual production of Tamiflu to 300 million treatments, 10 capsules per treatment, by 2007. It has 12 outside suppliers that can perform parts of the process.

Other vaccine manufacturers such as Chiron are pursuing alternative ways, namely to make vaccines that might help prevent people from getting bird flu.

In October this year, they announced that it has initiated a Phase I/II study of an investigational cell culture-derived influenza vaccine in the United States.

Production of influenza vaccine using cell-culture technology may offer significant advantages over traditional manufacturing methods by eliminating the dependence on chicken eggs for production.

The removal of egg supply lead times would enable flexible and faster start-up of vaccine production in the event of an annual vaccine supply shortfall or an avian influenza pandemic.

However one major disadvantage is of course, cost. Changing to cell-based vaccine manufacturing could cost the company billions of dollars.

The other major vaccine manufacturer, Sanofi-Pasteur has entered a series of contracts designed to speed the production process for new cell culture influenza vaccines.

Only this month, Sanofi Pasteur, had entered into an agreement with the French Ministry of Health to produce pre-pandemic vaccine in 2005 against the H5N1 avian strain.

The deal would mean a stockpile of 1,400,000 doses of vaccine would be created. The agreement also commits the company to being ready to provide enough vaccine for 28 million people in the event of a pandemic being declared, once the actual virus strain responsible has been identified.

Sanofi Pasteur is the only vaccine manufacturer to participate in FLUPAN, an EU-funded collaboration that is intended to improve the level of pandemic preparedness in the EU.

Under the terms of the agreement, Sanofi Pasteur is to produce a vaccine to combat another strain with pandemic potential (H7N1) that will be used in a FLUPAN clinical study.

source: drugresearcher

Vaccine producers’ resources meet pandemic demand

The surge in vaccines against influenza has surprised Governments across the world, with the stark admission that demand was unforeseen. Avian flu, which has emerged as a real threat to humans, has not only have added to the danger but has put vaccine manufacturers under increased pressure to meet the demand.

Concerns over growing cases of avian flu and the possibility of a flu pandemic have led to more people than usual seeking vaccination against seasonal flu, even though this would not protect against a pandemic strain.

News of how the UK government was caught short in the wake of an impending pandemic is surprising, considering the media hype fuelling public concerns about the bird flu pandemic threat.

The UK's Department of Health (DoH) currently meets vaccine manufacturers each year to discuss requirements based on previous demand and other factors, which need to be taken into account.

The understanding was based on 11 million people being at risk, but was recently revised to 13.2 million.

The Department of Health said the 14 million vaccine doses ordered by GPs from manufacturers and held in a contingency pot by government had all been used. The department has ordered 200,000 more doses, but those will not be available until 2006.

Influenza vaccines need to be changed, generally each year, to cope with mutations and this need to change vaccine formulations results in delays when flu breaks out.

Human flu is caused by two influenza strains, A and B. The killer bird flu virus H5N1 is a derivative of the A strain. The pandemic vaccine is being developed to tackle the A strain while the universal vaccine should act against A and B.

Vaccine manufacturers have certainly learnt the lessons of last year, when fingers were pointed at producers such as Roche and GlaxoSmithKline. This year has seen considerable time and effort invested into stepping up production to meet demand. Roche makes Tamiflu and GSK an inhalable drug called Relenza.

Samantha Christey, manager, GSK Biologicals World Wide, told In-PharmaTechnologist.com: "Recently GSK has invested $2 billion to expand the company's flu vaccine manufacturing capacity and to increase the production of its antiviral Relenza (zanamivir for inhalation). Both could help meet public health needs in the case of pandemic."

"The company expects to increase its North American manufacturing capacity with the proposed acquisition of ID Biomedical, a Canadian vaccine manufacturer," she added.

Special preparations to cope with the expected demand include an investment of € 94.3 million to double production capacity for its Influsplit/Fluarix flu vaccine at its Sachsisiches SerumWerk (SSSW) plant in Dresden, Germany.

Christey added: "GSK will build a second plant at the site and increase its annual production capacity from 35 million influenza vaccine doses per year currently, to 60 million doses annually before the end of this decade."

Meanwhile Roche's response to the flu outbreak has resulted in production reaching full capacity. Almost all governments have ordered it, and thus demand may not be satisfied.

Roche had commented that it might allow other companies or governments to make it under licence.

"More than 200 requests from third parties have been received to date and Roche production experts have already been in initial talks with 8 companies, amongst them large generic manufacturers and major pharmaceutical companies, as well as with a number of governments, including Taiwan and Vietnam," the company said.

"The goal is to be in a position to select potential partners for more detailed discussions by the end of November."

The company has also said it hopes to be able to step up its own annual production of Tamiflu to 300 million treatments, 10 capsules per treatment, by 2007. It has 12 outside suppliers that can perform parts of the process.

Other vaccine manufacturers such as Chiron are pursuing alternative ways, namely to make vaccines that might help prevent people from getting bird flu.

In October this year, they announced that it has initiated a Phase I/II study of an investigational cell culture-derived influenza vaccine in the United States.

Production of influenza vaccine using cell-culture technology may offer significant advantages over traditional manufacturing methods by eliminating the dependence on chicken eggs for production.

The removal of egg supply lead times would enable flexible and faster start-up of vaccine production in the event of an annual vaccine supply shortfall or an avian influenza pandemic.

However one major disadvantage is of course, cost. Changing to cell-based vaccine manufacturing could cost the company billions of dollars.

The other major vaccine manufacturer, Sanofi-Pasteur has entered a series of contracts designed to speed the production process for new cell culture influenza vaccines.

Only this month, Sanofi Pasteur, had entered into an agreement with the French Ministry of Health to produce pre-pandemic vaccine in 2005 against the H5N1 avian strain.

The deal would mean a stockpile of 1,400,000 doses of vaccine would be created. The agreement also commits the company to being ready to provide enough vaccine for 28 million people in the event of a pandemic being declared, once the actual virus strain responsible has been identified.

Sanofi Pasteur is the only vaccine manufacturer to participate in FLUPAN, an EU-funded collaboration that is intended to improve the level of pandemic preparedness in the EU.

Under the terms of the agreement, Sanofi Pasteur is to produce a vaccine to combat another strain with pandemic potential (H7N1) that will be used in a FLUPAN clinical study.

source: http://www.drugresearcher.com

Total Number of Human Cases of Bird Flu Reaches 131: WHO

Since December 2003, the total number of confirmed human cases of H5N1 bird flu has reached 131, 68 of them fatal, the World Health Organization (WHO) said Thursday.

Vietnam, with 92 confirmed human cases and 42 deaths, remains to be the country most severely hit, according to the WHO website.

Vietnam is followed by Thailand, which has 21 cases and 13 deaths.

Indonesia has confirmed 11 cases and seven of them were fatal.

Cambodia has confirmed four cases, all fatal.

And in China, three human cases of bird flu has been confirmed.

(Source: Xinhua)

China reports another human death from bird flu

BEIJING (Reuters) - China said on Wednesday that a 35-year-old woman farmer had died of bird flu, its second confirmed fatality from the virus.

The Xinhua news agency, quoting the Health Ministry, said the woman had developed fever and pneumonia-like symptoms on November 11 after contact with sick and dead poultry in the eastern Anhui province. She died on November 22.

Xinhua said tests by China's Centre for Disease Control and Prevention had proved positive for the deadly H5N1 strain of avian influenza.

A poultry worker from Anhui died of bird flu on November 10.

The health ministry has reported the new confirmed case to the World Health Organisation (WHO). It has also informed the authorities in Hong Kong, Macau and other countries.

H5N1 has killed 67 people in Asia since 2003, and both the World Bank and Asian Development Bank have warned of the huge economic costs of a human pandemic should the virus mutate into a form that can spread easily among people.

For now, the virus is hard for humans to catch.

"There is no proof of human-to-human transmission of bird flu in the world so far," Chen Xianyi, head of the contingency office in the Ministry of Health, told Xinhua in an interview.

Another confirmed case in China, a nine-year-old boy, survived infection while his dead sister is a suspected case.

Anhui province on Tuesday ordered all domestic poultry to be raised in pens or cages in a bid to curb the spread of bird flu.

Some 50 million Chinese households raise poultry, mainly in backyards, yet the average number of birds raised is just 19, he said, citing a Chinese government survey.

Canada orders cull of 60,000 birds

OTTAWA, Nov. 20 (Xinhuanet) -- The Canadian Food Inspection Agency (CFIA) on Sunday ordered the precautionary killing of about 60,000 birds at a commercial farm in the province of British Columbia where a H5 strain of bird flu was found.

Tests have confirmed the duck from a commercial farm in Chilliwack in the Fraser Valley, east of Vancouver, has a non-lethal strain of avian flu, CFIA's veterinarian Cornelius Kiley told reporters at the town on Sunday.

Initial tests last week found a H5-type strain in the duck during routine tests. The CFIA immediately quarantined the farm which houses about 60,000 ducks and geese.

The federal agency is expanding the quarantine from one farm to50, and four farms within a five-kilometer radius of the affected farm are under special surveillance, Kiley said.

He said there was no indication the virus has spread beyond thefarm, which was also subject to an avian flu poultry cull last year, adding all indications are that the virus is not a "particularly nasty strain."

More testing will be done at the National Center for Foreign Animal Disease in Winnipeg to confirm which strain was found.

On Saturday, the CFIA said two wild ducks in Manitoba have tested positive for H5N1 viruses, but not the dangerous strain that has spread from birds to people in Southeast Asia.

Officials called the viruses "low pathogenic," meaning they arenot viewed as a public health threat.

The viruses were isolated as part of a cross-country surveillance program to find what avian flu viruses are being carried by wild ducks in Canada. A H5N3 subtype was also isolated in two birds from the province of Quebec. Enditem

source: www.chinaview.cn

China reports its first cases of bird flu in humans; 1 dead

Beijing - China reported its first human cases of bird flu on the mainland Wednesday, including at least one fatality, as health workers armed with vaccine and disinfectant raced to inoculate billions of chickens and other poultry in a massive campaign to contain the virus.

The World Health Organization confirmed that the virulent strain experts fear could cause a worldwide flu pandemic has now infected humans in the world's most populous nation.

China's Health Ministry reported confirmed cases of infection with the deadly H5N1 strain in a poultry worker, who died, and a 9-year-old boy, who fell ill in central Hunan province but recovered, the official Xinhua News Agency said.

It said the boy's 12-year-old sister, who died, was recorded as a suspected case.

Experts worry the virus could spread and mutate in China because of its huge poultry flocks and their contact with humans. It also has migration routes for geese and other wild birds that might carry the disease.

"This is a psychologically telling moment for a country that has never had bird-flu cases in the past in humans," said Roy Wadia, a WHO spokesman in Beijing. "This will drive home to citizens across the country that this can happen in our own backyards."

Officials had warned a human infection in China was inevitable after the country suffered 11 outbreaks in poultry over the past

month, which prompted authorities to destroy millions of birds.

Elsewhere in Asia, the H5N1 strain has infected at least 126 people and killed at least 64 of them since 2003, two-thirds of them in Vietnam.

Nevertheless, WHO spokeswoman Maria Cheng in Geneva said the Chinese cases do not increase the risk of a flu pandemic because there has been no observed genetic change in the virus and no apparent spread between people.

She said it would not be surprising if more human bird-flu cases are confirmed in China.

"There are a lot of chickens infected and there's a lot of contact between humans and chickens in China," she said.

The Chinese government announced plans Tuesday to vaccinate all the country's 14 billion domestic fowl.

It wasn't clear how long that would take.

According to health officials, vaccinating chickens can require repeated injections and booster shots. State television showed workers at poultry farms jabbing chickens with injector guns.

By Joe McDonald
source: The Associated Press

Vietnamese scientists decode gene of bird flu virus

Vietnamese scientists have decoded the gene of H5N1 virus, paving the way for defining the variations and transmission mechanism of the bird flu virus, local newspaper Youth reported Wednesday.
Vietnam's Ho Chi Minh City Pasteur Institute and the Regional Veterinary Centre in the southern city claimed Tuesday they have entirely decoded the gene of the virus.

Ngo Bao Long, of the Veterinary Centre, said they found not only the virus strain H5, but also two other strains of H3 and H4 in two samples from poultry.

Theoretically, when a fowl is infected with H5, H3 and H4 at the same time, the viruses can swap their genes to create a new virus strain, which can be more dangerous, he said.

Vietnam, in early 2006, is likely to churn out 20-50 million dozes of H5N1 vaccines to be used for poultry next year, said the biotechnology institute's director Le Tran Binh, adding his institute has completed procedures to produce the vaccines.

Meanwhile, the country's National Institute of Hygiene and Epidemiology is completing final procedures to produce H5N1 vaccines to be used for people. The Hanoi-based institute that has been involved in research into the vaccines since 2004, has proposed the health ministry use them on trial basis in early 2006.

Since December 2004, Vietnam has detected 65 human cases of bird flu infections, including 22 fatalities, according to the health ministry.

--Xinhua

source: (IANS)

Kuwait reports first bird flu; spreads in Asia

KUWAIT CITY (AP) - A flamingo found on a Kuwaiti beach had the strain of bird flu that has devastated poultry stocks and killed more than 60 people in Asia - the first known case of the deadly bird flu in the Arab world.

Also Friday, Thailand reported an 18-month-old boy was suffering from bird flu, and China reported two new outbreaks in poultry.

Mohammed al-Mihana of Kuwait's Public Authority for Agriculture and Fisheries said tests showed the flamingo had the deadly H5N1 flu strain, while a second bird - an imported falcon - had the milder H5N2 variant.

Al-Mihana said the imported bird, which had been quarantined at the airport, was a falcon, not a peacock as reported Thursday. Both the flamingo and falcon were destroyed.

Officials in this small oil-rich Persian Gulf state said there was no indication bird flu had spread to humans and they saw no need to slaughter domestic bird stocks. Poultry and eggs from local farms were free of the disease, they said.

Al-Mihana said teams would continue to fumigate farms and bird markets and are checking places where birds stop on their migration from Asia to Africa.

There have been worries about outbreaks of bird flu in the Middle East because the region sits on important migratory routes. Migratory birds earlier spread the virus to Russia, Turkey and Romania.

The H5N1 strain has generated fears of a pandemic should it mutate into a form transmissible among humans. So far, humans have caught the virus only from infected birds.

The ailing Thai toddler was recovering in a hospital. His family's house in a Bangkok suburb was also home to three fighting cocks and a chicken, Dr. Thawat Suntarajarn said. All the birds died soon after the toddler was hospitalized, Thawat said.

Twenty-one people in Thailand have caught bird flu, and 13 have died.

China on Friday reported additional outbreaks - the seventh and eighth in the country. No human cases have been reported in China.

One of the new Chinese outbreaks was in Liaoning province northeast of Beijing. It occurred Sunday and killed 300 chickens, the Chinese Agriculture Ministry said in a report on the Web site of the Paris-based International Organization for Animal Health. Some 2.5 million birds were reported destroyed.

The other bird flu outbreak occurred Nov. 2 in Jingshan County in Hubei province, killing 2,500 poultry and prompting officials to destroy more than 31,000 birds, China's official Xinhua News Agency said.

Vietnam - which has suffered two-thirds of Asia's human deaths from the virus - ordered its military and police to help fight the disease.

Also, North Korea issued a bird flu alert Thursday, exhorting people to unite against a potential outbreak, making chicken farms off-limits to outsiders and requiring feed transport vehicles to be disinfected.

H5N1 first appeared in Hong Kong in 1997 but was curbed when authorities destroyed all poultry in the territory. It re-emerged in December 2003 and has recently spread from Asia to Europe.

By DIANA ELIAS
Associated Press Writer

Italy finds mild form of feared virus in duck

ROME - Italy has found a form of the H5N1 virus in a wild duck, but the Health Ministry said on Thursday it was not dangerous and bore no relation to the strain of Asian avian influenza that has killed more than 60 people.

The H5N1 virus was identified on Wednesday in a testing centre in northern Italy, the health ministry said. It added the virus was genetically similar to strains frequently found among wild waterfowl in Europe, and not highly pathogenic.

"There is no alarm. There is no new concern," ministry official Elisabetta Alberti Casellati said.

"The case of H5N1 identified yesterday ... has nothing to do with the cases of Avian influenza registered in Asian countries, because it deals with a low pathogenic strain."

The virus was found in only one bird in the more than a thousand tested so far, the ministry said.

The testing centre said in a statement that the wild duck carrying the strain of H5N1 was identified in Modena province in northern Italy. It said the virus was "unaggressive" and "not dangerous to humans".

The bird was tested after a hunter had killed it.

Italy has reported no cases of the deadly Asian avian flu virus, which is endemic in poultry across Asia. It has been found in birds in eastern Europe and there are fears migrating flocks could spread it around the globe.

More than 60 people have died from bird flu and scientists fear it could mutate into a form easily transmissible between humans and cause a global flu pandemic that could kill millions.

An official at the UN Food and Agriculture Organisation told Reuters it was possible for Italy to have registered a form of the H5N1 virus that had no relation to the Asian strain.

"That is possible. When we look at H5N1, not all of them are the same," said Juan Lubroth, a senior officer at the FAO's animal health service.

"What you would need to look at is some sequencing analyses to look at the genes the virus is carrying."

- REUTERS