Investigational New Drugs

, Volume 31, Issue 2, pp 479–487 | Cite as

Clinical trial design in biosimilar drug development

  • G. Dranitsaris
  • K. Dorward
  • E. Hatzimichael
  • E. Amir


In contrast to most drugs which are chemically synthesized and have a known structure, biological drugs are derived from living organisms or their products. Biologicals are structurally more complex and unique from chemically synthesized small drug molecules because of their larger size and intricate manufacturing process. Secondary to their protein structure, they are also more prone to acute and chronic immune responses. Biosimilars are intended to offer comparable safety and efficacy relative to reference brand biologicals, yet they are not generic alternatives to the original compounds and so are currently not considered interchangeable. Given their structural complexity, multifaceted manufacturing processes and risk for immunogenicity, biosimilars require class-specific regulatory approval pathways. Here we seek to provide a general overview of clinical trial design in the era of biosimilar drug development. This will include a review of the regulatory requirements for clinical trials in Europe and the United States, followed by a review of two biosimilars that have recently reported results of randomized trials against branded biologicals.


Biosimilars Follow on biologics Regulations Non-inferiority Clinical trial 


Authors contributions

G. Dranitsaris: wrote manuscript, literature review

K. Dorward: literature review, edited manuscript

E. Hatzimichael: literature review, edited manuscript

E. Amir: literature review, edited manuscript

Declaration of competing interests

None of the authors have competing interests to declare. This review did not receive any funding.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • G. Dranitsaris
    • 1
    • 2
    • 3
  • K. Dorward
    • 1
    • 2
  • E. Hatzimichael
    • 1
    • 2
  • E. Amir
    • 1
    • 2
  1. 1.Department of HaematologyUniversity of IoanninaIoanninaGreece
  2. 2.Department of Medical OncologyPrincess Margaret HospitalTorontoCanada
  3. 3.TorontoCanada

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