Definition
Like all biologics, biosimilars are extracted from living organisms and undergo highly complex and regulated manufacturing processes. A biosimilar is highly similar to, and has no clinically meaningful differences in safety, purity, and potency from an existing FDA/EMA-approved reference product.1
Regulatory Perspectives
FDA: A biosimilar is a biologic product that is highly similar to a reference product notwithstanding minor differences in clinically inactive components and has no clinically meaningful differences between the biologic product and the reference product in terms of safety, purity, and potency of the product.2
EMA: A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. A biosimilar demonstrates similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety, and efficacy based on a comprehensive comparability exercise.3
Key Terms
Extrapolation: It is a well defined scientific and highly regulated principle whereby the biosimilar is approved for use in indications, held by the reference biologic, but not studied for the biosimilar in direct head-to-head clinical trials. This process is based on the "totality of evidence" provided in the biosimilar's application and should support clinical equivalence in at least one sensitive indication shared with the reference product.
Interchangeability: Based on the EMA definition, interchangeability refers to the property of a medicine to be exchanged with another one, which is expected to have the same clinical effects. This may mean replacing a reference product with a biosimilar or vice versa or replacing one biosimilar with another. Such replacing may be done by switching or automatic substitution at the pharmacy level. In the United States, interchangeability is a legal designation which means products can be substituted for the reference product by a pharmacist without the intervention of the prescribing health care practitioner, if so permitted by state laws. As per this definition, the FDA MIGHT require additional scientific validation.
1. FDA. Biological Product Definitions. Available at: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.fda.gov/files/drugs/published/Biological-Product-Definitions.pdf. Accessed October 24, 2022.
2. US FDA. Biosimilar product regulatory review and approval. https://www.fda.gov/files/drugs/published/Biosimilar-Product-Regulatory-Review-and-Approval.pdf. Accessed February 2022.
3. European Medicines Agency. Biosimilar medicines: overview. European Medicines Agency. Accessed: February 2023. Available at: https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medicines-overview.
