Clinical trial development for biosimilars.

OBJECTIVES: Discuss issues regarding clinical trial design for the development of biosimilars in the European Union and the United States, with special focus on monoclonal antibodies used in the treatment of inflammatory diseases.

METHODS: A search of the Internet as well as PubMed was conducted through June 2014 for information related to the clinical development of biosimilars using the keywords biosimilar, rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis. The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) websites were searched for biosimilar guidelines.

RESULTS: The EMA began issuing draft guidelines for the development of biosimilars almost a decade ago and has approved numerous biosimilars. The US FDA has issued draft guidances providing stepwise considerations for the nonclinical and clinical development of biosimilars but has yet to approve a biosimilar under this pathway.

CONCLUSIONS: Clinical trials aim to resolve uncertainties that may remain following nonclinical development regarding the similarity of the proposed biosimilar with the reference product. Pharmacokinetic and pharmacodynamic studies form the backbone of early clinical development and serve to inform phase 3 clinical development. Factors to be considered in clinical development include study population, design, end points, sample size, duration, and analytical methods.