Essential characteristics and clinical study requirements for the approval of biosimilar products in the EU and USA
| Characteristic | FDA and EMA requirements | ||
|---|---|---|---|
| Primary amino acid sequence | One amino acid change respective to the innovator will deny biosimilarity | ||
| Potency | Must match the reference product | ||
| Route of administration | Must be the same as the reference product, although the administration device may be different | ||
| Higher-order structures, post-translational modifications and other potential variants | Must 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 parameter | FDA | EMA | |
| Pharmacokinetic studies | Comparative human studies | Single dose, comparative human studies | |
| Pharmacodynamic studies | Comparative human studies, where clinically relevant measures are available | Combine with PK studies where a clinically relevant PD endpoint is available. Otherwise non-clinical evaluation required | |
| Efficacy | At least one, adequately powered equivalence* trial | Highly sensitive, dose-comparative PD studies may be sufficient. Otherwise, at least one, adequately powered equivalence trial | |
| Safety | At least one, adequately powered equivalence trial | At least one, adequately powered equivalence trial | |
| Immunogenicity | At least two comparative trials, one pre- and one postmarketing | Must 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.