Biotechnology is used to produce medicinal products for complex therapeutic purposes (recombinant human insulin, erythropoietin, granulocyte colony-stimulating factor, etc.) when they cannot be synthesized chemically or produced in sufficient amounts from biological material by simple extraction. Major therapeutic advances have been made using biotechnological methods, prominent among which is recombinant DNA technology, by which sequences of natural or intentionally modified genes are inserted in a suitable host system, which then expresses the product of interest. The host production system can be a prokaryotic or eukaryotic organism, an animal or a transgenic plant. Biotechnology-derived medicinal products have reached a crossroads in their short history. The expiry of patents protecting innovative recombinant products introduced over the last two decades means that manufacturers with the required know-how and technology can develop and market substitutes. Against this backdrop, a recently published EMEA Directive stipulates what is required to demonstrate that a biotechnological medicinal product, or ‘biosimilar’, is equivalent to the original drug. The new European text marks a significant change with respect to previous EMEA Directives concerning ‘replicas’ of innovative products. Directive 2004/27/EC1 states that a biosimilar is first and foremost a medicinal product which has similar physicochemical and biological properties to the reference product, and the same pharmaceutical form. But the most remarkable measure stipulates that new preclinical and clinical trials must prove a biosimilar to be bioequivalent to the innovator's original drug. If a biosimilar has more than one indication, its safety and efficacy must, where necessary, be demonstrated for each of the claimed indications. This obligation to demonstrate identical safety and efficacy is not necessarily applied to conventional generic drugs, whose equivalence is taken as given if the copy has the same bioavailability as the original. It is therefore clear that the legislators wished to put biosimilar medicinal products in a different category from generic drugs. This distinct status is linked to the very nature of the therapeutic product, and to the risk of modification due to minor, difficult-to-detect alterations in the numerous steps of the production process. Biotechnology-derived therapeutic products are generally proteins with a complex structure. In comparison, chemically synthesized products are far simpler molecules. Biotech products may also contain additional hydrocarbon chains, which may be required for their pharmacological activity. The production of a given protein by two types of cells, which are necessarily different genetically and enzymatically, can lead to quantitative and qualitative variations in glycosylation. The industrial production of biotechnology-derived medicinal products involves many steps that are susceptible to variations: culture of cell line in bioreactors, extraction of crude protein, purification and formulation for delivery as medicinal products. Biosimilars and the original product may both contain impurities, but not necessarily the same ones. All this explains why variations in a protein are seen following a change in production site or method, even when this protein is produced by the same manufacturer using clones of the same cell bank. Potential variations are even greater when the protein is produced by another manufacturer, especially as product innovators quite legitimately protect their industrial secrets. Even minor variations can alter the activity, pharmacokinetics, or pharmacodynamics of the products. This is why the regulations demand proof of the efficacy and safety of biosimilars before they are granted a marketing authorization.