Table 5

Essential characteristics and clinical study requirements for the approval of biosimilar products in the EU and USA

CharacteristicFDA and EMA requirements
Primary amino acid sequenceOne amino acid change respective to the innovator will deny biosimilarity
PotencyMust match the reference product
Route of administrationMust be the same as the reference product, although the administration device may be different
Higher-order structures, post-translational modifications and other potential variantsMust be as similar as possible to the reference product, with adequate analyses to demonstrate that any differences do not impact upon clinical efficacy, safety or immunogenicity
Clinical study parameterFDAEMA
Pharmacokinetic studiesComparative human studiesSingle dose, comparative human studies
Pharmacodynamic studiesComparative human studies, where clinically relevant measures are availableCombine with PK studies where a clinically relevant PD endpoint is available. Otherwise non-clinical evaluation required
EfficacyAt least one, adequately powered equivalence* trialHighly sensitive, dose-comparative PD studies may be sufficient. Otherwise, at least one, adequately powered equivalence trial
SafetyAt least one, adequately powered equivalence trialAt least one, adequately powered equivalence trial
ImmunogenicityAt least two comparative trials, one pre- and one postmarketingMust be assessed during the safety trial
  • *Differences in the specified parameters and the 95% CI fall within a predetermined equivalence margin, demonstrating that the biosimilar is both ‘non-inferior’ and ‘non-superior’ to the reference product.

  • EMA, European Medicines Agency; FDA, Food and Drug Administration; PD, pharmacodynamic; PK, pharmacokinetic.