Background Paper on Biosimilars

Biological medicinal products (“biologics”) are made from a living system or organism. Similar biological medicinal products (“biosimilars”) are follow-on versions of original biotechnological compounds. They are developed independently following expiry of the original products’ patents, generally by companies other than the original manufacturer. A genetically modified cell line usually forms the base material for most biologics. Each manufacturer uses its own, characteristic and unique cell line (host cell) with which it then develops a unique manufacturing process in order to produce the drug in question.

A biosimilar should have exactly the same effect as the reference medicinal product and treat the same diseases as the innovator product. However, biologics have a lower bioavailability than classical (chemically produced) medicines because of their molecular size. As a result, they must be administered parenterally. Because of the size of their molecules, the human body’s reaction to the presence of xenobiotics (the “immunogenic response”) must be carefully tested and monitored to ensure that patients can enjoy the intended product benefits safely. These ongoing validations and tests during the complex manufacturing process and the administration of biotechnological medicinal products are time-consuming and necessary. The aim is to provide the maximum level of patient safety as the highest priority.

On account of the special features that characterise a biological medicinal product, the European Union has decided that the designation and authorisation procedure of follow-up products of biological medicinal products (“biosimilars”) should be different than that applicable to chemical medicines (“generics”).

The definition, authorisation and marketing of similar biological medicinal products are the topics of an intense debate. The discussion focuses on the difference between similar biological medicinal products and the generic copies of standard chemical medicines. As chemical medicinal products, generics are clearly defined in terms of structure and contain identical copies of the original active substance. From a pharmaceutical perspective, the original and generic compounds can hardly be distinguished from each other. They meet the strict criteria of “equivalence” in the organism, particularly as regards safety and effect. This equivalence between the original and generic product must be proved in a critical trial (proof of “bioequivalence”). In contrast, the above-mentioned definitions cannot be used for the follow-up products of biological medicinal products due to their individual features and the complexity of their manufacturing process. Analytical and preclinical trials are not enough to prove equivalence or an identical character between two biological products.