Are Biosimilars Identical to the Reference Products

Abstract

Biotechnological drugs have become an essential part of modern pharmacotherapy and are expected to reach a 50% share in the pharmaceutical market in the next few years. The recent and pending patent expirations for a number of biopharmaceuticals (e.g. human growth hormone, erythropoietin, interferons ,etc.) have led to the development of alternative versions of biological products called biosimilars or follow-on biologics (FoB). As with traditional low molecular weight chemically derived pharmaceuticals, this allows the possibility of developing new and cheaper versions of biopharmaceutical products. However, it is important to state that whilst biosimilar products are similar to the original product, they are not exactly the same and may not be biogenerics. “Interchangeability” is a term used to designate the situation where scientific data convincingly demonstrates that two products with very similar molecular compositions or active ingredient (s) can be safely substituted for one another and have the same biologic response and not create adverse health outcomes. With small molecular products, there is a long history to support the use of various scientific approaches to establish “bioequivalence” between products with the same active ingredient (s) produced by different manufacturers. Bioequivalent products can indeed be expected to behave in a pharmacologically interchangeable manner, when used in patient care. With protein products, as of today, the FDA has not determined how interchangeability can be established for complex proteins. Different large protein products, with similar molecular composition, may behave differently in people and substitution of one for another may result in serious health outcomes (e.g. generation of a pathologic immune response). Biosimilars are attempted copies of existing biological medicinal products, but the unique multidimensional structure of the proteins and in consequence their complicated mode of action are not easily reproducible. In fact biotechnological medicine, even with the same type of cells or microorganisms, can possess different pharmacokinetic and pharmacodynamic properties. Recombinant proteins are completely different from chemical small molecule drugs in terms of their manufacturing, structure and action. Biotechnological drugs are large molecules with a fragile-3-dimensional structure and are products of living cells and usually contain a mixture of different isoforms. Chemical drugs are more stable, whereas biological drugs are sensitive to change in physical conditions which require not only strict manufacturing processes but also appropriate storage at pharmacies and by the patients. Manufacturing and formulation of protein products is highly complex and lengthy and the manufacturing process is critical in terms of defining the characteristics of the final product. These products are usually much more difficult to characterize than chemically derived ones, and past experiences has shown that even minor differences can have important clinical consequences. For all these reasons European Agency for the Evaluation of Medical Products (EMEA) has named these products biosimilars, and not generics or biogenerics. As a direct consequence the approval process that is used for generic drugs cannot be applied to drugs claiming similarity to biopharmaceuticals. The history of the development of regulatory laws in the case of biosimilars is short, due to the fact that expiry of patent protection for major biological medicines took place in the recent years. In fact EMEA is a pioneer in the regulations on biosimilars, since FDA is still working on the guideline on Copyright © 2009 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services Iranian Journal of Pharmaceutical Research (2009), 8 (2): 77-78