The vaccine, manufactured by sanofi pasteur was found to be able to develop adequate immunity against H5N1 in 45 percent of the people receiving two doses of the vaccine.  

The vaccine is not intended to fully prevent bird flu infection when an influenza pandemic emerges, which may be caused by a variant that is immune to the vaccine.

Instead, the vaccine is to provide "early limited protection in the months before a vaccine tailored to the pandemic strain of the virus could be developed and produced."

"The threat of an influenza pandemic is, at present, one of the most significant public health issues our nation and world faces," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs.

"The approval of this vaccine is an important step forward in our protection against a pandemic."

The H5N1 virus, one version of the influenza A virus commonly found in birds, is far more severe than seasonal influenza and the infection happens quickly, with pneumonia and multi-organ failure commonly seen.

No human case of H5N1 has been reported in the United States while almost 300 people worldwide have been infected with this virus since 2003 and more than half of them have died.

Experts and the government officials fear that the current H5N1 influenza virus may someday mutate into a strain that can readily spread from person to person, potentially infecting millions of people worldwide and killing tens of hundreds.

"The timing and severity of an influenza pandemic is uncertain, but the danger remains very real," said Jesse L. Goodman, M.D., M.P.H., Director of FDA's Center for Biologics Evaluation and Research.

"We are working closely with other government agencies, global partners and the vaccine industry to facilitate the development, licensure and availability of needed supplies of safe and effective vaccines to protect against the pandemic threat."

The vaccine is made of a human strain and is intended for immunizing people 18 through 64 years of age who could be at increased risk of exposure to the H5N1 influenza virus contained in the vaccine.

To immunize people against H5N1, two injections of the vaccine approximately one month apart are needed.

The H5N1 vaccine will not be sold commercially.   For the time being, the manufacturer, sanofi pasteur Inc. makes the vaccine only for the U.S. government for inclusion within the U.S. Strategic National Stockpile for distribution by public health officials if needed.

The FDA approval is based on the results of a clinical study of 103 healthy people who received two shots of 90 micrograms of the vaccine with 28 days apart. Additional 300 healthy people received two doses lower than 90 micrograms per injection and additional 48 received a placebo.

According to the study, 45 percent of individuals receiving the 90 microgram, two-dose regimen developed adequate amounts of antibodies, which are expected to reduce the risk of getting influenza.
 
The remaining individuals may also have some protection against bird flu and have the potential to help reduce disease severity and influenza related hospitalizations and deaths even if their antibody levels were below the optimal level.

The vaccine was well tolerated and the most common side effects include pain at the injection site, headache, general ill feeling and muscle pain.

More information on this H5N1 influenza vaccine is being collected on safety and effectiveness in other age groups and will be available to FDA in the near future.

A more potent bird flu is being developed by Sanofi Pasteur and other manufacturers with the support of FDA and the U.S. National Institutes of Health and other government agencies.

For now, the FDA approval and availability of this vaccine will enhance national readiness and the nation's ability to protect those at increased risk of exposure to H5N1 influenza virus.

The U.S. Strategic National Stockpile is maintained by the U.S. Centers for Disease Control and Prevention and large quantities of medicine and medical supplies can be delivered to any states within 12 hours.

1. What is the Food and Drug Administration (FDA) announcing?

FDA is announcing the licensure of the first vaccine in the United States for humans against the H5N1 influenza virus, commonly referred to as avian influenza or "bird flu." This inactivated influenza virus vaccine is indicated for immunization of persons 18 through 64 years of age who are at increased risk of exposure to the H5N1 influenza virus subtype contained in the vaccine. This vaccine is derived from the A/Vietnam/1203/2004 influenza virus. The vaccine is manufactured by sanofi pasteur Inc. of Swiftwater, PA and has been purchased by the federal government for inclusion within the Nation's Strategic National Stockpile.

The approval and availability of this vaccine is an important step in enhancing the Nation's readiness against a possible pandemic and enhances our ability to protect those at increased risk of exposure to the H5N1 virus.

2. What is avian influenza?

Avian influenza - the "bird flu" - is a virus that infects wild birds (e.g., ducks and gulls) and domestic poultry (e.g., chickens and turkeys). There are numerous different strains of avian influenza; however, most do not cause illness in people. Only influenza A viruses naturally infect birds. Wild birds are the natural host for all subtypes of influenza A virus. In general, wild birds do not get sick when they are infected with influenza virus, but some avian viruses can cause serious disease and death in wild birds. However, domestic poultry, such as turkeys and chickens, can get very sick and die from avian influenza. H5N1 is a newer, more recent strain of avian influenza, and is currently the main cause of concern among the scientific and medical community with regard to its potential to cause a pandemic. The H5N1 strain can infect birds, other animals and people.

3. What is an influenza pandemic?

An influenza pandemic is a global outbreak of disease that occurs when a new influenza virus appears in the human population, causes serious illness, and then spreads easily from person to person. It can sweep across a country and around the world in a very short time. Like the seasonal influenza many people get every year, pandemic influenza will probably spread by infected people coughing or sneezing or by touching something with the influenza virus on it and then touching their mouth or nose. Unlike seasonal influenza, people will have little immunity to the virus that causes a pandemic. An influenza pandemic will likely cause more severe illness, even death, and affect more people than seasonal influenza.

It is difficult to predict when the next influenza pandemic will occur or how severe it will be. In the past century, pandemics occurred in 1918-1919, 1957-1958 and 1968-1969.

The H5N1 strain of the avian influenza virus has caused the largest number of reported cases of severe disease and death in humans of any avian influenza viruses and is a potential candidate for starting the next pandemic.

Wherever and whenever an influenza pandemic starts, everyone around the world is at risk for getting the disease. Countries might delay arrival of the virus through measures such as border closures and travel restrictions, but these measures are not likely to totally protect the population.

4. Has anyone been diagnosed with avian influenza?

There have not been any human cases of avian influenza in the United States or North America, but there have been cases in other parts of the world such as Asia and Africa. According to statistics provided by the World Health Organization, from 2003 through April 11, 2007, there have been 291 laboratory-confirmed cases in humans, of whom, 172 died. Each additional case provides the virus an opportunity to improve its ability for human-to-human transmission and develop into a pandemic strain. But right now, there is no pandemic influenza in the world.

5. Is avian influenza more serious than seasonal influenza?

Yes. H5N1 or avian influenza has some of the standard seasonal influenza symptoms such as high fever, headache, and muscle aches, but people quickly become seriously ill and pneumonia, difficulty breathing, and multi-organ failure have been common among people who have been stricken with H5N1 influenza.

6. How well does the influenza virus vaccine, H5N1, work?

One multi-center, randomized, double-blinded, placebo-controlled, dose-ranging study in healthy adults, 18 to 64 years of age, investigated the safety and immunogenicity of the vaccine. A total of 103 healthy adults received a 90 microgram dose of the vaccine by injection, followed by another 90 microgram dose, 28 days later. In addition, there were approximately another 300 healthy adults who received the vaccine at doses lower than 90 micrograms and a total of 48 who received placebo by injection.

Of the various doses tested, the study showed that the 90 microgram dose had the better immune response, meaning that at this particular dose, the vaccine induced the most antibodies in the blood against the H5N1 influenza virus strain. The 90 microgram two-dose regimen produced levels of antibodies expected to reduce the risk of getting H5N1 influenza in 45% of those who received it. Although the remaining individuals did not develop this level of antibody, current scientific information on other influenza vaccines, suggests that less than optimal antibody levels may still have the potential to help reduce disease severity and influenza-related hospitalizations, and deaths.

7. Why didn't the clinical trial include more people?

FDA recognizes that a limited number of people were studied in the clinical trial. The study was designed by the National Institutes of Health (NIH) as an exploratory study to look at the amount of antibodies generated in humans from various doses. Because the results showed promise for providing protection against the H5N1 influenza virus and helping with national preparedness for influenza pandemic, sanofi pasteur submitted a Biologics License Application to FDA.

Although each 90 microgram dose required to stimulate the immune response was twice the amount that is used in the seasonal influenza vaccine, the manufacturing process and vaccine formulation for the H5N1 vaccine is the same as that of sanofi pasteur's US licensed seasonal vaccine, which has a long record of safety and effectiveness.

It is fortunate to have this vaccine during this "inter-pandemic" phase. The benefit of having a licensed vaccine against a potential pandemic influenza virus strain, even with limited data, outweighs the risk of having no vaccine at the time of an inevitable influenza pandemic.

8. What are the risks associated with the vaccine?

The vaccine was generally well-tolerated by the recipients in the study, with pain and tenderness at the injection site, headache, general ill feeling, and muscle pain being the most common complaints. However, because the number of people studied was small, rare safety events may not have been identified, but given the potential risk of a pandemic, this is the only vaccine currently available and its benefits outweigh its risks. In addition, sanofi pasteur has agreed to work with the U.S. government to gather additional information on the safety and effectiveness of the vaccine should it be used in the event of a pandemic.

9. How will FDA monitor the safety of a pandemic influenza vaccine if it is used?

Post-licensure monitoring of vaccine safety involves identification of possible adverse effects of vaccination, followed by evaluation of these "signals" for a possible causal link with vaccines. Systems currently available to conduct vaccine safety monitoring include the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). Adaptation of these systems for use during a pandemic may be required. Other large automated databases of encounter and/or claims data that might be useful for pandemic influenza vaccine safety monitoring include those of the Centers for Medicaid & Medicare Services, Veterans Affairs, Department of Defense, and private insurance groups not currently part of the VSD. The FDA and the Centers for Disease Control and Prevention (CDC) are evaluating these systems for potential to contribute to the monitoring of pandemic influenza vaccine safety. If the pandemic vaccine is administered primarily through public health departments, a registry of vaccinees, with common identifiers allowing researchers to determine the vaccination status of those with adverse events (AE), may need to be established.

10. What if a pandemic is declared and the influenza virus strain of the pandemic is different than the influenza virus strain in this vaccine?

No one can predict which influenza virus subtype (strain) will cause the next pandemic. Several factors affect the effectiveness of influenza vaccines. One major factor is the degree to which circulating strains and influenza vaccine strains are similar. If the pandemic virus strain is substantially different from the H5N1 virus contained in the vaccine, it is unlikely that the existing vaccine would be effective. It is possible that the next influenza pandemic will be caused by a strain of influenza that does not belong to the H5N1 subtype. Both of these scenarios would require development of a new vaccine. If the influenza pandemic strain turns out not to be a perfect match with the vaccine strain, it does not necessarily mean that the vaccine can't be used; studies have shown that influenza vaccine may provide some immunity against strains that are somewhat different.

The goal of pandemic preparedness is to develop additional vaccines and vaccination strategies that will be ready for use against various strains that have the potential to cause a pandemic.

11. Does the vaccine contain thimerosal?

Yes, thimerosal, a mercury containing compound, is used as a preservative in the vaccine. Because the vaccine is supplied in a multi-dose vial; it is necessary to have a preservative to prevent the growth of bacteria and fungus in the event that the vaccine is accidentally contaminated, as might occur with repeated puncture of multi-dose vials.

12. Will the vaccine be available to anyone who wants it?

No, the manufacturer has stated that the vaccine won't be available to the public commercially, meaning it can't be obtained from a doctor's office. It has been purchased by the federal government for inclusion within the country's Strategic National Stockpile, for distribution by the Department of Health and Human Services in case it is ever needed.

13. Why is the vaccine for inclusion within the Strategic National Stockpile ( SNS) and not being made available to all Americans?

The production capacity of the United States currently is not sufficient to make vaccine rapidly available for the entire population. Inclusion of this vaccine in the SNS will ensure that when it is needed, those who are designated as priority recipients, will have vaccine available to them. Other vaccines are also being developed to meet the Nation's needs against influenza pandemics.

14. Even though it will be in the SNS, can people who may be at risk of exposure to H5N1 influenza virus, such as travelers to infected regions of the world, poultry workers, or first-responders get the vaccine?

At this time, immunization is not recommended for populations that may be at risk of exposure to H5N1 influenza virus. Through its Interagency Pandemic Vaccine Prioritization Working Group, the federal government is working to decide who will get the vaccine earliest in a pandemic.

15. Why does the approved indication not include children or elderly?

It is not uncommon for new vaccines to be tested in a healthy adult population and then once further information is gathered about benefits and risks, additional testing is done in other populations such as children and the elderly. FDA is expecting information on these particular populations to be submitted in the near future and will evaluate those results.

16. How is the vaccine administered?

It is administered as a two-dose regimen. One 90 microgram dose is given intramuscularly, in the upper arm, and a second 90 microgram dose is given in the same manner, 28 days later.

17. Is it possible to become infected with avian influenza from the H5N1 vaccine?

No. The vaccine is made from killed influenza viruses, and they cannot cause influenza infection.

18. Will the annual shot for influenza protect people against pandemic influenza?

No, current annual influenza vaccines include three influenza viruses, A subtypes H3N2 and H1N1 viruses, and one B virus. A vaccine made from these viruses would not provide protection against a different influenza A subtype virus (such as H5N1).

It is important to continue to get the influenza shot every year as this is the best way to prevent illness from the seasonal influenza virus.

19. Where can I get more information on avian influenza and actions that can be taken to prepare for a pandemic?



Information can be found at www.pandemicflu.gov. This website provides one-stop access to U.S. Government avian and pandemic flu information and is managed by the Department of Health and Human Services. In addition, information can also be found on FDA's website at http://www.fda.gov/oc/op/pandemic/default.htm

Updated: April 17, 2007