This case demonstrates the sensitivity of the novel drugs. And it just one of many conceivable scenarios. Hormones such as EPO or immunostimulants such as interferon are huge biomolecules that are produced by living cells cultivated in large bioreactors. The starting point is a gene that is introduced into the cell. The latter then expresses this gene in the form of a chain of amino acids — a protein. The genetic construction code is by no means the complete recipe, however. Instead, it is much more the case that the cells further modify the protein. They may add sugar molecules or other molecular groups to the protein, for example. All of these modifications affect the way in which the protein chain folds into its final ball-like three-dimensional configuration, and thus determine the gigantic molecule’s external appearance. Aspirin, for example, contains just 21 atoms that are joined together in a molecule that is always identical. EPO, by contrast, is almost 200 times heavier and its exact chemical composition has not yet been exactly described.

“It is not possible to create an exact copy of a biological active ingredient, due to the different cell cultures used and the complex production processes involved,” says Thomas Bols, Vice President Health Policy & Market Access at Merck Serono. However, healthy competition between manufacturers is very much desired by statutory health insurance funds and governments, which is why a regulatory framework conceived by the European Medicines Agency (EMA) has been in effect for a number of years. The manufacture of so-called biosimilars — similar biological medicinal products — is now permitted if their similar degrees of effectiveness and safety can be demonstrated. The clinical studies required are similar to those needed for a new approval process, but are less comprehensive. “The development costs generally amount to between 200 and 300 million euros, whereas the equivalent costs would typically be in the region of two to three million for conventional generics,” says Bols.

Where generics are concerned, the companies’ objective is to develop a “me-too” drug as soon as possible after the original compound’s patent protection has expired, while the drug’s price is falling drastically. However, as far as biosimilars are concerned, only a handful of companies are capable of manufacturing them, and their price normally falls by just around 30 percent. Nonetheless, since 2006 a good dozen biosimilars have received approval in Europe. By contrast, the introduction of a comparable regulatory framework was still being debated in the U.S. at the end of 2010. “The products approved by the EMA fulfill the normal safety standards, even though — unlike original products — there is no data from long-term studies of the biosimilars,” says Bols. In his opinion, physicians should always remain free to decide whether to prescribe the original or a biosimilar. The patient should then be informed of this choice and its possible effects. This is standard practice in most countries in Europe. At the same time, many countries have taken a stand against the automatic substitution of biological active ingredients in the same manner as traditional chemical drugs. Where possible, patients should always receive the identical active ingredient, as such an approach helps to avoid side effects that could be triggered by small differences in the product.