Evolution on biosimilar guidelines worldwide

Biosimilars are biological medicinal products marketed as a copy of an originator (reference) product. Today, biosimilars are a reality of the pharmaceutical market in the European Union. The scenario is complicated by evolving regulatory policies, mainly established by guidelines issued by different authorities, and periodically revised to reflect the experience gained. Unlike generics, which contain the same (small molecule) active substance(s) as that of a reference medicinal product and have a bioequivalence demonstrated through appropriate bioavailability studies, biosimilars, are demonstrated to be similar but not identical to their reference products. Indeed, their chemical characteristics are directly related to the manufacturing process, and cannot be precisely duplicated lead to a final product with different characteristics. Moreover, since no analytical techniques are currently available for detecting or predicting all biological and clinical properties of proteins, differences between biopharmaceutical products can easily remain undetected. Thus, to grant a Marketing Authorization (MA), biosimilars require an approach different from both originators and generics and a comparability exercise is required (abridge application). EMA has issued guidelines about evaluation of biosimilar products in general or product-specific guidelines which describe the specific studies required to compare efficacy and safety between a originator and a biosimilar product containing a specific active substance, e.g. erytropoietin and low-molecular-weight heparins. The World Health Organisation (WHO) has recently published a guideline about evaluation of biosimilar products, while Food and Drug Administration (FDA) has issued some drafts. Other issues about biosimilar products are the naming, the pharmacovigilance and the possibility of substitution. The WHO has regulate the naming of biological active substances, while the issue of the substitution and interchangeability has been left to the national authorities.