TABLE 1

U.S. Regulatory Approval Requirements for Biosimilars: Comparison With U.S. Requirements for Small-Molecule Generics and to E.U. Requirements for Biosimilars

Drug typeBiosimilarsSmall molecule genericsBiosimilars
SettingUnited StatesUnited StatesEuropean Union
Regulatory agency1FDAFDAEMA
Approval pathway regulationBiologics Price Competition and Innovation Act of 2010Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act)Directive 2004/27/EC of 2004
Approval requirements2• Analytical (in vitro) studies: demonstrate “highly similar” chemical composition, purity, and quality to the reference product• Toxicity studies on animal model• Comparative clinical studies on patients with the clinical condition: demonstrate safety and effectiveness, assess immunogenicity, elucidate pharmacokinetics and pharmacodynamics• Bioequivalence studies: demonstrate same chemical composition, purity, and quality as the reference product and same bioavailability in healthy volunteers• In vitro assays and impurity profiling• Comparative clinical studies on patients with the clinical condition: demonstrate safety and effectiveness, assess immunogenicity, and elucidate pharmacokinetics and pharmacodynamics• Post-approval pharmacovigilance/ monitoring studies
Criteria for granting interchangeability3 (defined as allowing for the drug to be substitutable for the reference product by a pharmacist without the intervention of the prescriber)• Fulfillment of all criteria for biosimilarity• Clinical “switching” studies: demonstrate same clinical result in any given patient and demonstrate that risk from switching is not greater than from using the reference product aloneAutomatically granted upon fulfillment of bioequivalence criteria described above• Fulfillment of all criteria for biosimilarity• Additional studies not required• Decisions made at the country level
Nonproprietary naming of product4USAN-designated proper name of the biologic plus a four-letter suffix devoid of meaningSame USAN-designated proper name as the reference drugSame proper name as the biologic as designated by the INN convention5
Number of Approved Biosimilar Products as of December 2019626NA69
  • 1 The EMA was the first regulatory agency to establish a pathway for biosimilar approval. 2The specific requirements for biosimilar approval may vary on a case-by-case basis for both the FDA and the EMA. 3The FDA has recently modified the criteria for interchangeability for the specific case of insulins, such that proof of biosimilarity will be sufficient for granting interchangeability. 4The nonproprietary names of all reference biologics approved by the FDA as of March 2020 will also contain a four-letter suffix devoid of meaning, which is different than the suffix of their biosimilars. 5The INN is defined by the World Health Organization and typically adopts the same name as the USAN-designated name. 6As of December 2019, the FDA had not approved any interchangeable biosimilar products. INN, International Nonproprietary Names; USAN, United States Adopted Names Council.