Several European countries have banned a flu vaccine produced by the Swiss pharmacetucial company, Novartis, for safety reasons. DW looks at the production of flu vaccines to show how this could have happened.
Germany is the latest country to announce a ban on flu vaccines from the Swiss pharmaceutical giant Novartis, following previous moves by Italy, Switzerland and Austria. On Thursday, Germany's vaccine regulatory agency, the Paul Ehrlich Institute, announced that the release of four batches of the vaccine Begripal and a batch of Fluad had been canceled.
Every fall, doctors and health experts appeal to the public to be innoculated against the common flu. But the relevant vaccines are nothing like regular medicines because producing them is very tricky. After vaccination, the body's immune system should be able to recognize the characteristic attributes of the pathogen, or infectious agent, and then remember it at a later date.
Vaccines are made up of bacteria, viruses or characteristics from them. For live vaccines, against diseases like yellow fever and measles, the pathogens can still multiply, but do not infect people.
More is good with vaccines
Like the name implies, pathogens in dead vaccines are killed with chemicals. Most of the time, a virus can be reduced to a single surface protein. Then the protein can be injected. That's the case for the Hepatitis B vaccine.
But producing any kind of vaccine requires the propagation of viruses or bacteria in a laboratory. That takes time because not every pathogen grows quickly. And with some, researchers have to ensure that the bacteria and viruses are carefully monitored. The pathogens need the right nutrients, temperature and environment to multiply. Pathogens also change their preferences for optimum conditions now and then, especially in the case of flu viruses. That means that researchers again have to find the best growth conditions.
Bacteria can be grown in a culture medium in large pots. But unlike bacteria, viruses are not living organisms, because they always need other cells in order to multiply. Therefore, drug manufacturers make vaccines against viral illnesses with animal cells in petri dishes. The virus infects the cells and reproduces, and at the end, scientists can obtain the final pathogen from the culture. It is the first intermediate product in vaccine production. Then, the virus must be extracted and purified.
For example, viruses can be reproduced in the connective tissue of chickens, or cells obtained from people. Originally, the cells were only from humans or animals. But now, they have become pure laboratory cells because they are manipulated in such a way as to reproduce like cancer cells. With time, through mutations, the viruses adapt to fit the host.
“The trick is to get viruses, which can reproduce in these cells, but which have not changed so much that they are no longer good for the vaccination,” says Rolf Hömke from Germany's Association of Research-Based Pharmaceutical Companies (VFA). The vaccines would not produce the desired immunity in the body, he adds.
If manufacturers have a matching strain of the virus, they must ensure that there is as little change as possible. The solution is to freeze huge amounts of the virus in portions and to thaw them for every new production process. That's the reason why vaccines are produced in batches and never continuously, Hömke says. This prevents an optimal virus strain from changing further.
“For almost all vaccines, the serum that you get today is almost the same as 20 years ago,” he says. The only exception is the flu vaccine.
Every year brings new viruses
The flu virus changes so fast that there are always viruses with new characteristics. So last year's flu vaccine may not be effective against a flu strain that is rampant this year.
The World Health Organization (WHO) keeps on eye on influenza viruses. It sends the three most common strains to vaccine manufacturers so that they are part of the vaccine for the new season. GlaxoSmithKline, a major pharmaceutical manufacturer, reproduces flu viruses in fertilized and developing eggs.
“Flu viruses infect birds, and a chicken's embryo is the most primitive bird,” says Hömke.
The viruses can then be extracted from a part of the embryo of a developing chick. One egg is about enough for one dose. The three virus strains are propagated separately and then mixed in the vaccine.
In time for the new flu season, pharmaceutical companies have to discover the best conditions in which different virus strains propagate and then produce sufficient pathogen material. There are years when one or more strains do not propagate, and that means that there is less vaccine, or that the vaccine comes late. In other years, the yield is good.
Not enough for everyone
The manufacturer must test each batch of a vaccine after production to check whether it works and if test animals develop antibodies against the pathogen. Apart from that, the vaccine needs to meet a wide range of quality standards – It must be absolutely clean and sterile. It's quite possible, however, that the desired immune response fails, or that the vaccine demonstrates unwanted side-effects in the animals, or is contaminated.
“There's nothing that the manufacturer can do, but dry the batch and burn it,” says Hömke.
When that happens, there are delivery problems because another batch cannot be produced if one is destroyed after several months of production, which can take 6 to 22 months due to the required extensive testing and controls.
If more people suddenly wanted to get vaccinated, there would be bottlenecks. The supply can't be easily adapted to the demand, says Hömke.
“You can't just fire up the copier when there are only a few originals,” he said..