Genotropin- a miracle medicine that makes dwarves grow tall

Kalle Ljungkvist is 187 centimeters tall now and a university student who studies physics at Uppsala University in Sweden. His parents found that something was wrong when he did not have the energy of other four-year-olds. Later he was diagnosed to produce too little growth hormone. At the age of five, Kalle began to take daily injections of growth hormone. At the age of 17, he stopped the medication. This is just one example how a patient who otherwise would not grow, became as tall as a normal person due to the growth hormone-Genotropin produced by Pfizer Strangnas, Sweden. Pfizer has 65 thousand similar patients around the world, about 30 or 40 percent of the total market of 180 thousand patients. This year Pfizer's miraculous drug Genotropin - the human growth hormone - celebrates its 20 years anniversary of production.

How did the growth hormone Genotropin come into being?

The human growth hormone Genotropin (www.genotropin.com) is used to treat children and adults who for one reason or another do not produce the hormone themselves. Without the treatment, a child could only grow to 125-140 centimeters while after treatment, the person can grow as tall as 180 cm. For adult patients who lacks growth hormone the treatment gives a possibility to come back to a normal active life.

There were three revolutions for Genotropin to be widely used for relevant patients. First, in the 1960s, the pharmaceutical industry had made hormone products from the pituitary glands of human dead bodies. Located at the base of the brain, the pituitary gland controls the body's functions and metabolism via the hormones it produces. But these hormone products were vulnerable to contamination from human viruses spreading deadly disease and thus was stopped in the mid 1980s.

Researchers in Sweden had already decided to try to develop a production method of a substance which is identical to the growth hormone produced by the human body and the development was intensified in the early 1980s. Linda Fryklund, PhD, Associate Professor, has concentrated on hormones and the genetics of growth in her career at Kabi, Pharmacia, and later Pfizer. She led the group that originally developed Genotropin at the Swedish company Kabi.

Linda Fryklund

"We started in 1978, and there were all sorts of problems at the very beginning. But two years later, in 1980, we found we could produce something active from the bacteria and we saw it respond in rats. We chose the well-known bacteria E. coli as the host organism for the hormone production and we then knew that we were able to produce the hormone", said Dr. Fryklund enthusiastically. But the next question was how to make it pure. The purification process is a very important step to make a drug. After numerous tests and failures during the process development, they could make it more than 99% pure, Fryklund continues to say.

Swedish authorities approved Genotropin in March 1987. This was considered the second revolution when biosynthetic growth hormones became available. This revolution substantially lowered the production cost, and made it possible to treat anyone with growth hormone deficiency as well as to test treatments on new groups of patients. With treatment, all patients could lead normal lives with normal height, muscle mass and skeletal strength, according to doctors. The third revolution was the invention of the Genotropin injection pen so that any patient who is even just six or seven years old can use it and inject themselves every day. That became the key to a global success for Genotropin. The drug was available, and the way to take it was simplified. Without the pen, patients had to go to the doctors three times a week. With the pen, the patients could inject themselves every day.

Open-minded leadership and trust make us work better

Dr. Fryklund said their success benefited from their bosses' trust and empowerment of the employees. "At that time we could use up to 2 million Swedish kronor without asking for permission first. This saved us a lot of time and energy so we could concentrate on research and development. We were at the time a small company, so we had to be quicker and better than the others."

In addition to financial support, Fryklund said researchers must trust themselves and be persistent in what they are doing. "Sure at the beginning we had a lot of problems and failures. We had to do it again and again, but we believed that we could make it work." said Fryklund.

Competitiveness is all important for a site leader

Working for Pfizer for 23 years, and just two and half years here in Str?ngn?s, 45 minutes by train west of Stockholm, Mr Orchard Pfizer Strangnas Site Leader, said he likes to work here and will work hard to decrease the costs and make the factory even more competitive.

"Yes, Pfizer indeed looks at countries such as China and India for production.

But Strangnas has its advantage in technology and provides a good infrastructure crucial for biotechnical production. Perhaps Pfizer likes to keep some of its technology in the west. But it is very challenging indeed for us. I told my staff that taking an example that in India they generate about 1500 PhDs a year in the biotech field, while here in Sweden only about 50. So we must work hard, lower the cost and make ourselves really competitive."

Simon Orchard Pfizer Strangnas Site Leader

Pfizer is not just producing Viagra

In China when people mention Pfizer, they often think of Viagra. But in fact, Pfizer all over the world produces many drugs treating high blood fat, blood pressure and many other diseases. In Sweden, a new factory is being built outside the old factory in Strangnas. Mr. Orchard said the capacity of the new factory will be much bigger than the old one. But it doesn't mean that they will hire more people. It only means that they have the ability to produce more with a similar number of people. They will close down the old plant when the new factory is up and running.

In addition, they will introduce a new production line which will produce a medicine similar to the growth hormone, but has the opposite function. The product will be used to treat Acromegaly, a condition where the body produces excess growth hormone, leading to abnormal growth of the body, notably in the hands, jaw and long bones.

As a site leader, Mr. Orchard said his biggest challenge is still to lower the cost and maintain or improve the product quality. "The biggest challenge I think is really over the next couple of years, giving all the support we need to start up a new factory and at the same time run this factory and decrease production cost and make it an even better place to work at. So running this factory and make it more efficient is the big challenge and on top of that, start up a new factory and make it running well is actually quite tough. I am confident to do it. But we must be very creative in how to use the people and their best skills." said Mr. Orchard.

Environmental effect is also high on the agenda

Dr. Fryklund said that as early as the 1980s, they already paid great attention to environment impacts. And they don't want the genetically modified micro-organism to go to the environment. "We were very strict with environmental rules." recalled Fryklund.

Mr. Orchard said that they have got the certificate of ISO 18001 in environment criteria. For example, all the waste water from the factory will go to the water treatment plant before the water is released to the nearby lake and much of the site waste is recycled. He said there is still potential in some areas. "One area we can do more is to look at the impact of transport, transport of people how they come to work and transport of our product and our raw materials coming here. We understand the impact and the better way of doing it. We haven't really done that and there is potential here. We have to look at the equipment we choose according to the recommendation list and try to avoid more carbon-dioxide emissions."

"Open dialogue and open culture is important. It is perfectly welcome for anyone to ask questions, to challenge things. Every second month we go out with questionnaires to the employees about how they feel about their work and ask them to answer 9 questions. In this way we encourage a continuous dialogue between the employees and the management. We also stimulate people to formulate suggestions for improvements of the production and we have innovation teams open for everybody. We try to help people to be more responsible about what they are doing. It is not just me the site leaders' responsibility, we are all responsible for what goes on here."

Experts believe that Genotropin has a broader market potential. Dr. Fryklund said she believes that there will be more patients who use this medicine because it is not only used for babies who lack growth hormone, but also used for adult accident survivors. To cover more patients, they need to spread the knowledge among doctors and hospitals all over the world so that they know the treatment is available. She believes that the economic benefit for the society is also huge if patients are cured.

But facing the globalization trend, Mr. Orchard said, whether the factory will move to China or other countries like what has happened in electronic and car industries, will very much depend on how competitive they will be in the future. They are expanding now in Strangnas, and they will try to keep it as competitive as ever, said Mr. Orchard.

By Xuefei Chen, People's Daily Online correspondent in Stockholm.