The United States—Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) has recently approved the first biosimilar of ranibizumab (ranibizumab-nuna, Byooviz, Biogen, USA) [1, 2]. The International Retina Biosimilar Study Group (Inter BIOS Group) had conducted a survey (Bio-USER-unpublished data) which revealed that many retinal physicians from Europe and the US have concerns regarding the safety and efficacy of biosimilars. Safety and efficacy are the major parameters on which biosimilar molecules are tested. Biosimilarity needs to be established which leads to the similar efficacy and safety of these drugs. In this paper, we will discuss the yardsticks which are defined by the regulatory agencies (FDA and EMA) that make sure these drugs are similar to the originator (reference molecules) in all aspects except for some differences which are not clinically meaningful. It is a stepwise approach consisting of the following steps [3, 4].

This is one of the most important steps for companies that are involved in the development of biosimilars as this step decides the remaining steps to prove the biosimilarity of the proposed product. This does not require clinical testing rather the structure of the proposed biosimilar molecule is analysed with the help of analytical methods. The structural analysis includes matching the primary structures such as amino acid sequences, secondary, tertiary, and quaternary structures including aggregation, posttranslational modifications, and biological activities of the protein chains such as glycosylation and phosphorylation with the reference molecule. Apart from these, other potential variations such as protein deamidation and oxidation are also assessed. Chemical modifications such as PEGylation sites and other characteristics are tested as well. The above-described structural analysis is to be performed in multiple lots to check variability. Additionally, the structural analysis should include excipient, process-related impurities, and stability. It is mandatory that the company should have state of the art technology for the characterization of references of the proposed biosimilar products [3, 4].

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD