© freelance tekstforfatter Christian Nevado On research and development in modern pharmaceutical companies eller Pharmaceuticals: A guided tour from lab to drugstore counter eller 7 years and 700 millions: how a modern drug is developed Poul Rasmussen, director of research and development at Leo Pharmaceutical Products in Denmark, describes the process any new drug must go through to make sure it's safe for you The popular notion of a research chemist wearing a white smock and juggling test tubes is not too far from the mark. Pharmaceutical research and development involves chemists working with compounds and bioscientists working with biological matter like receptors, enzymes and cell systems. It involves toxicologists making sure the product is safe, pharmacists turning it into pills, and doctors testing whether it's better than current products, doing statistics and clinical experiments.      All of these scientists work closely together with hundreds of colleagues at universities all around the world, trying to find 'leads' to the development of new products.      But even though the universities contribute greatly to the research part, only the industry has the resources to develop a product and put it on the market. Because that is an incredibly long, difficult and expensive process.      The research, development, testing and approval of a new drug with full documentation takes, on average, seven years and costs no less than 700 million DKK, often much more. This figure does not even include the research, only the development. So it's important to make plans for each stage of the process.      Who invests these huge sums of money? Pharmaceutical research and development is carried out under a private capitalistic system, allowing private companies, including the pharmaceutical companies themselves, of course, to support the research and development of new drugs. Sometimes a company might choose to go public with the financing, allowing anyone interested to invest in an upcoming product. Pharmaceutical companies: maybe competing, but still helping each other out Obviously, competing pharmaceutical companies are often working towards the same goals. We would all like to develop a remedy for cancer, or AIDS, or for one of a dozen life-threatening diseases. Searching for this, pharmaceutical companies often join forces on larger projects, exchanging knowledge and distributing tasks among each other, thus reaching the goal sooner and avoiding to duplicate each others' efforts. In general, knowledge about new findings in our field is very freely exchanged, for example through publications like Nature and Science or at scientific meetings and congresses. This also makes it possible for scientists to make a name for themselves, taking the credit for discoveries which are rightfully theirs by going public with them.      Still, this policy of making information easily accessible to others doesn't mean that we are gullible in this business. Before publishing new inventions, a patent application is filed, giving the discovering company exclusive rights to the production. In this way, we all support each other without giving away too many advantages. The story of Regaine: how decreased blood pressure became increased hair growth Sometimes the search for a cure for one ailment leads to the unexpected discovery of a cure for another. This is one of the positive effects of the extensive testing that is required during the development of each new product.      At Leo Pharmaceuticals, we were working on a drug back in the seventies to decrease blood pressure. We developed a product which did this by affecting the so-called potassium channels in the cell walls, opening them to relieve the pressure.      When we performed clinical trials with the product, we discovered an unexpected side effect: the patients got undesirable hair growth. It seemed that the effect on the potassium channels of the body extended to the potassium channels in the hair roots, stimulating growth, so we had inadvertently created a drug which could cure baldness in some people.      Interested in the new effect, we kept working on the principle and ended up with the product which is today undergoing clinical trials comparing it with Minoxidil. The story of Drivonex: How an improved vitamin D did wonders for skin and bone Back in the seventies, there was a problem with kidney patients who contracted bone problems. It turned out that this was because they lost their ability to make use of the vitamin D, which you take in through food, pills or even sunlight.      But before the body can use the vitamin D, the kidneys must make a small change in the molecules of the vitamin, adding a so-called OH group. The kidney patients, who were receiving dialysis treatment, couldn't do this, so Leo Pharmaceuticals developed a vitamin D molecule in which the OH group was already added. This solved the problem, and the patient's bones became normal again.      During further research, it was discovered that the vitamin D has other interesting properties as well. The vitamin has an active part which is able to influence the development of cells. This was interesting in connection with cancer cells. Cancer cells start out as normal cells, but stop developing before maturity and start multiplying instead. When we applied the active part of the vitamin D to a cancer cell, it became more normal: the cell finished its development instead of multiplying. So we tried to develop a vitamin D compound which had no bone-altering effect - but learned that in its present form, it was broken down by the body and could not be used against cancer.      It had another use in relation to abnormal cells, though. Psoriasis is a skin disease which is also caused by the uninhibited growth of immature cells. But with psoriasis, the breaking down of our vitamin D by the body was not a problem; it was an advantage, because it prevented the product from affecting anything but the skin itself. The resulting product, Drivonex, is one of our biggest today.      At Leo Pharmaceuticals, we are of course continuing our work with vitamin D and its possible uses against cancer. The story of penicillin: Discovered by one of medical history's luckiest coincidences As you may know, penicillin was originally discovered more or less by coincidence in 1928 by the bacteriologist Alexander Fleming. A piece of mould fungus blew in through an open window in his laboratory - which by modern standards was somewhat less than immaculate - and ended up in a petri dish containing a culture of bacteria. Gripped by curiosity, Fleming studied the culture through his microscope and saw that the fungus was killing the bacteria. His studies based on this discovery lead to the development of penicillin.      An anecdote tells that Sir Fleming years later was escorted through a modern laboratory by a colleague who proudly pointed out the expensive equipment and high hygienic standards. "What wonderful things couldn't you have discovered here!" exclaimed the colleague.      "Penicillin," answered Fleming laconically.      The first penicillin had to be injected into the body because the stomach acids destroyed its effect when it was taken in the form of pills. So the first step was for the industry to develop a penicillin pill.      Then it turned out that the penicillin only affected some kinds of bacteria, the so-called gram-positive bacteria, and not the gram-negative. So the second step was to develop a more broad-spectred penicillin.      Then the bacteria began to mutate, that is to change their properties so they were no longer affected by the penicillin. (This was - and is still - a problem, particularly in some countries where penicillin is sold without prescription and is used very indiscriminately.) So the third step was to develop a penicillin which could kill off these mutated types of bacteria. And so on...      This just shows that the development of a new drug is a constant process in which the preconditions are constantly changing and new efforts are required to keep up. Of course, the documentation on the drug has to be updated also. In practice, you talk about a first generation drug in the same sense as a beta version of new software. This version is then improved upon by yourself or others, gradually eliminating the weaknesses and side effects as they are discovered. The whole process might never be finished because new factors constantly enter into the equation. So it is hard to underestimate the amount of work involved in the development of a new drug. What the pharmaceutical business do to consider the less fortunate Because the research and development of new drugs is so expensive, very few countries have the resources for it. Only Western Europe, Japan and North America can afford it in any organized way. But even though pharmaceutical development is a business like so much else, we have room for considering the less fortunate countries. Several large companies donate medicine to underdeveloped nations. Smithkline Beecham is an example of a company which has been very generous in this respect, and the WHO is constantly working to improve the distribution of vital drugs worldwide.      The governments are also conscious of the need for developing medicine against less common diseases, which of course is not so profitable, and they support the development of these so-called "orphan drugs" as much as they can. They often help the developing companies to get exclusivity on the market during the introduction of an "orphan drug".      There is no doubt that without applied pharmaceutical research and development, the world would look much different. Without the birth control pill limiting the number of new individuals and other medicine prolonging the life span, we would have a lot more young people and a lot less old people. How we make sure that pharmaceutical products are safe Safety is a very important factor in the development of any new pharmaceutical product. Everyone is interested in control and reliability, and each country has its own set of rules for documenting a product's properties to the authorities. This set of rules is called GMP (Good Manufacturing Practice) and ensures that the product always retains its approved properties and that everything is done right when you use it.      A data sheet must follow any pharmaceutical product, describing exactly what it is, for what use it is approved and what the side effects are. There must be no doubt about these things. This data sheet is under constant revision; new discoveries about the product are added on the sheet, and both the prescribing doctor and the patient have to abide by it. It is the doctor's responsibility to report any side effects a product has, both to the authorities and to the company which has developed it.      At Leo Pharmaceuticals, we keep a constantly updated database with the side effects of our products and can print out a report on any product for the authorities at any time. Meaningful work is more fun at Leo Pharmaceuticals In a business where the cost of developing new products can be measured in the hundreds of millions of DKK, it is obvious that the largest pharmaceutical companies have great advantages. They are able to reduce their financial risk, invest in several projects at once and in general make life hard for mid-sized companies like Leo Pharmaceuticals.      Still, being our size also hasj its advantages. Working with a shorter chain of command, we are able to make decisions quicker and move faster. All in all, I believe that we balance the pros with the cons very well by keeping on our toes and making sensible decisions.      The pharmaceutical business involves so many different working areas, occuping so many different people with different backgrounds that the work never gets boring. The fascinating projects, the constant dialogue and the achievement of constructive results makes every day worth while. And in my personal opinion, there is not much work which is as meaningful as the daily effort of developing medicine for sick people.