Safety and toxicity of biosimilars-EU versus US regulation

Background: As patents for biological drugs begin to expire, the need for scientific guidance on biosimilar drugs grows increasingly important. The European Medicines Agency provided the first guidelines to cover the approval of biosimilars in 2005. On 10 February 2012, the US Food and Drug Administration drafted three guidance documents relevant to approval of biosimilars in the US. Objectives: The EU and US regulatory approaches to biosimilar approval were compared evaluating the potential impact on characterizing the safety profile of a proposed biosimilar product. Methods: Applicable legal documents and guidelines from the EU and US were compared. Three main categories were identified as potentially safety-relevant, namely general regulatory requirements, non-clinical and clinical testing strategies. Results: No fundamental differences were identified between EU and US guidelines concerning the non-clinical and clinical testing strategies. However, extrapolating immunogenicity data from one indication to another is allowed in the US but not in the EU. Further differences were identified in the general regulatory requirements including the reference product, definitions of biological drugs and historic regulatory conditions for distinct product classes. Furthermore, inconsistencies regarding naming and labelling conventions may hamper distinct post-authorization pharmacovigilance measures. Conclusion: Although the regulatory approaches to biosimilar approval in the US and EU are similar in general scientific content, the identified diff erences might affect the extent of the testing strategy and post-approval pharmacovigilance measures for biosimilars, in particular depending on the type of approval process (generic versus new drug application). In order to ensure globally comparable safety profiles, harmonization of these topics is highly desirable.