The Injection Business How Safe Is the Swine Flu Vaccine?
On first impression, anyone walking into the medical practice of Helmut Beermann these days would likely think the doctor must be a hypochondriac. A warning sign prominently displayed on the door to his practice in the southern section of Hannover in northern Germany reads: "People who believe that they could have the swine flu are barred from entering this practice." Instead, the sign instructs potential carriers of the virus to ring the doorbell four times and "wait outside for an appropriate period of time."
A GSK employee in Dresden working on the production of a vaccine for the swine flu.
Foto: DPALast week, someone rang the telltale doorbell four times. Beermann carefully covered his nose and mouth with a mask, stuck his head out the door and greeted the sick patient.
"I went to his house, where I took his temperature outside and determined he had a fever," says the 55-year-old doctor.
Beermann is less concerned about his own health than about his business. "The public health department has closed the practices of five doctors I know." The agency apparently justified its action with the argument that the physicians had treated swine flu patients without wearing protective clothing.
In theory, this rule also applies to the ordinary winter flu, but health officials are uninterested in that aspect of the regulation.
Now that Germany is in a pandemic state of emergency, overreactions among public health officers are not uncommon. In Lübeck, a port city on the Baltic Sea, they closed a delivery ward in a hospital. In Engstingen, a town in the southwestern state of Baden-Württemberg, an entire school was shut down, simply because seven pupils had become infected during a trip to London. And in Ilmenau in the eastern state of Thuringia, a concerned public health officer ordered a county-league football match cancelled because a striker had come down with the swine flu.
The officials have been incited by the sort of media hysteria typical of the summer news slowdown. Day after day, German mass circulation newspaper Bild, for example, recounts how many vacationers have contracted the swine flu on the Mediterranean vacation island of Mallorca, most likely during inebriated viral exchanges over communal buckets of sangria. One typical alarmist headline reads: "Swine Flu: Virus Out of Control!"
The headlines have been having an impact. On the eastern edge of the Lüneburg Heath region in north-central Germany, Heinz Jarmatz, a family physician, receives about 20 inquiries a day from nervous patients wanting to know whether a vaccine is available against the flu strain yet. Jarmatz would also like to put up a sign, expect that his, as he says, would read: "The Vaccine is Not Available Yet." He predicts that once the serum becomes available, "there will be a real stampede to get it."
Does It Pose a Health Risk?
But the question is: Is it even advisable to get the supposedly protective vaccination as quickly as possible? Is the swine flu vaccine truly safe? Or does it pose a health risk?
To avoid being accused of doing nothing, government health officials are preparing a vaccination campaign unprecedented in scope. Last Friday, the health ministers of Germany's states ordered 50 million doses of the vaccine from pharmaceutical giant GlaxoSmithKline (GSK).
But their plans do not call for the standard, tried-and-tested program of vaccinations that are administered to millions of Germans each year to combat the seasonal influenza virus. Instead, new types of vaccine production processes will be used, as well as new drugs designed to boost the immune system.
In addition, the vaccine serums have passed through a uniquely accelerated approval process at the European Medicines Agency (EMEA) in London. "What we are experiencing here is a large-scale experiment being conducted on the German population," warns Wolfgang Becker-Brüser, the publisher of arznei telegram, a professional journal critical of the pharmaceutical industry.
When the plans for an accelerated mass vaccination were developed, this approach seemed justified. In 2004, a new type of killer bird flu virus known as H5N1 made headlines when it became known that the resulting illness was fatal in 60 percent of those infected. Fortunately, the virus has not (yet) proven to be highly contagious from human to human. But if the bird flu virus ever mutates, a pathogen could develop that will spread quickly and be extremely deadly. If that happens, accelerated vaccination will undoubtedly be preferable to no vaccination, all risks aside.
But the swine flu virus, or H1N1, has not proven to be a killer on anything like the same scale. Although more than 1,100 people had died from swine flu by last Friday, according to official figures, most of the victims were people with underlying conditions, in some cases severe. Pregnant women also appear to be among those at particularly high risk. In the vast majority of cases, however, the symptoms of the swine flu have been noticeably mild.
"At first I thought to myself: Will I die?" said Rupert Grint, known for his portrayal of the character Ron Weasley in the "Harry Potter" films, after contracting H1N1. "But all I had was a sore throat." According to a survey conducted by the German medical journal Ärztezeitung, "almost all physicians in private practice note that the symptoms are generally moderate."
This has led to growing calls for a more cautious approach to dealing with the swine flu. "If the course of the swine flu remains as harmless as it has been so far, a mass vaccination program would not be justified," says Matthias Gruhl, the head of the public health department in the northern city of Bremen. According to Gruhl, who is involved in preparations for a pandemic, all efforts are based "on the assumption that a second, far more serious wave of the swine flu is headed our way." However, says Gruhl, there are no signs yet that this will in fact happen.
Many in the medical community share his reservations. "Countries need to assess carefully the risks and benefits of rapid approval" of an H1N1 vaccine, writes the British medical journal The Lancet in an editorial in its current edition, "especially since the disease has so far been mild with most patients making a full recovery."
The Lancet authors emphasize, in particular, the simplified approval procedure introduced in Europe specifically for vaccines to be used in a pandemic, which permits manufacturers to apply for approval of so-called "mock-up" vaccines in advance of a pandemic. Four such vaccines were available when the pandemic began. Now the mock-up virus strain merely has to be exchanged for the current pandemic virus, which would allow for approval to be granted within a short period of time. Under the accelerated procedure, safety studies with the vaccine that would be used in actual vaccinations are no longer necessary.
Pregnant Women at Risk
According to the EMEA guidelines, tests to determine the safety of the final vaccine must only be performed during mass vaccinations. In the case of a killer virus, such a massive human experiment would be an acceptable risk, but should this also be true of an illness that often causes nothing but relatively harmless cold-like symptoms? The European drug licensing authority appears to have recognized the problem, and in late June, the EMEA quickly tightened its requirements for the documentation of vaccination-related incidents and adverse medical effects.
But this does nothing to change the fact that the clinical tests completed with the model vaccines were not particularly stringent. The EMEA guideline merely calls for safety studies in which side effects can be detected that occur in more than 1 percent of cases. In other words, nothing is known about less common vaccine-related incidents, some of which can be quite serious.
In theory, this means that of the 25 million German citizens to be vaccinated in the first stage, close to 250,000 could suffer a serious reaction to the vaccine, one that may not have been detected in the preceding safety studies.
The subjects in the clinical trials were primarily adolescents and adults, but not small children and pregnant women. H1N1 poses a particularly high risk for the latter group, which should therefore be vaccinated first. Paradoxically, however, there are virtually no data on the effects of a new adjuvant -- a component used to stretch the active ingredient -- used in the GSK vaccine on pregnant women. For this reason, says an insider, pregnant women in the United States will receive a vaccine without the adjuvant.
Americans More Cautious than Europeans
Frank Ulrich Montgomery, the deputy head of the German Medical Association, finds the German approach surprising. "In a mass vaccination program like this, it is preferable to resort to proven methods and substances."
In fact, it would have been safer to use the conventional influenza vaccine, which has been used and proven safe millions of times, as the basis for the new swine flu vaccine. Instead, new production methods are also being tested. For the first time, flu vaccines that are not cultivated in chicken eggs but on cell cultures will be used on a large scale.
Novartis has already applied for approval in Europe of its pandemic vaccine based on cell cultures. "Approval is expected to be issued in mid-October," reports Johannes Löwer, president of the Paul Ehrlich Institute (PEI), the national control authority charged with approving vaccines.
Germans could also receive this cell-culture-based vaccine, if the German states decide to order a second batch of vaccine from Novartis instead of GlaxoSmithKline. However, the rapid market introduction has sparked concerns, because the viruses used to make the Novartis vaccine grow on dog cells, which can cause tumors in animal experiments. Consequently, it is critical that these cells not enter the eventual vaccine.
Other concerns have been raised about GlaxoSmithKline's new pandemic vaccine, which is expected to be available first. The vaccine contains an adjuvant known as AS03, which is added to amplify the immune response so that fewer killed swine flu virus cells are needed.
"This means that more doses of vaccine can be produced with less material. In addition, the vaccine is designed to protect against other mutated H1N1 viruses," says PEI President Löwer, who is quick to add: "The safety data look good." However, the data are not as comprehensive is Löwer implies. Besides, adjuvants are by no means as harmless as the name would suggest. A 57-member World Health Organization (WHO) panel concluded in early June that the effects on young children and women in the early stages of pregnancy required further study. The panel also noted that there were no clinical experiences that made it possible to assess the risks and benefits of adjuvanted and non-adjuvanted H1N1 vaccines.
The US agency charged with regulating drugs, the Food and Drug Administration (FDA), has thus far refused to approve flu vaccines containing adjuvants. Besides, Americans generally tend to be more cautious than Europeans. Although the Centers for Disease Control and Prevention (CDC) have recommended vaccinating 160 million US citizens, the US swine flu vaccine is based on a seasonal flu vaccine.
'There Are Still Some Unkowns'
To be on the safe side, US authorities are also stockpiling adjuvants. "If it turns out, in September or October, that the virus has become more dangerous, we will still be able to approve the adjuvants in an expedited process and then add them to the vaccine," explains Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which manages vaccine trials. Fauci also points out that his agency is "not as confident in adjuvants, because there are still some unknowns."
The Americans have good reason to be cautious. Their health officials still have uneasy memories of what the New York Times called the "swine flu fiasco" of 1976, when 13 soldiers at a military base contracted a new H1N1 virus and one of them died. Because of fears that the world could face a new flu pandemic almost as deadly as the 1918-1919 "Spanish flu," more than 40 million people were immunized with a hurriedly produced vaccine.
The pandemic never materialized, but instead there were many reports of presumed vaccine complications. One that was particularly insidious was Guillain-Barré syndrome, a neurological disorder that causes paralysis in the legs and can lead to severe pulmonary complications.
That experience prompted the FDA to establish stricter standards for the approval of new vaccines, requiring manufacturers to conduct costly studies with thousands of volunteers. Given these regulations, it is only too convenient for drug companies when new vaccines and production processes to combat swine flu are tested on millions of Europeans. Indeed, instead of having to pay for testing, the drug companies stand to profit handsomely from this approach.
It is already clear that GlaxoSmithKline will be the greatest beneficiary of the swine flu. According to information obtained by SPIEGEL, one dose of vaccine will cost €8.33 ($11.9), and GSK stands to earn revenues upwards of €410 million ($588 million) in Germany alone.
Costs Could Reach €1 Billion
And then there is the cost of administering the vaccine on such a large scale, which will not be borne by the health ministers who have ordered the vaccine from the pharmaceutical companies, but by Germany's health insurance agencies. This, at any rate, is the way German Minister of Health Ulla Schmidt, a Social Democrat, wants the cost issue to be handled. The "summary minutes" of a teleconference of state health ministers also call for the insurance companies to carry the full cost of vaccine administration.
The least expensive option, at least in cities, would be for public health agencies to implement the vaccination program. In that case, the authorities anticipate a markup of approximately €10 per person. It would cost an estimated two or three times as much if doctors in private practice administered the vaccinations and purchased the vaccine from pharmacies.
In the end, each of the German states will define its own procedure. Depending on how the vaccine is administered to the population, the program will cost the health insurance agencies between €650 million and upwards of a €1 billion for the amount of vaccine currently on order.
But things could actually turn out somewhat differently. Health insurance agencies will only pay for vaccines that are in fact administered, while the states will end up paying for unused doses. And perhaps the anticipated surge in demand for vaccinations will never materialize. "Imagine if we have a pandemic, and no one gets vaccinated," says a ministry official from one of the eastern German states.
MICHAEL FRÖHLINGSDORF, MARKUS GRILL, VERONIKA HACKENBROCH, GERALD TRAUFETTER