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Period: September to December 2012
In order to demonstrate comparability between a biosimilar and its reference product, EMA recommends that the clinical trial should make it possible to detect a difference between the biosimilar and reference product. In most cases, this means that a two-arm clinical trial design (reference biological and biosimilar) in a small group of homogenous patients may be used. If the two arms of the trial produce similar results, then the biosimilar can be approved.
The FDA guidelines go much further, however. The current text says that the biosimilar is ‘expected to produce the same clinical result as the reference product in any given patient’. The guidelines add that ‘the risk in terms of safety or diminished efficacy of alternating or switching between use of the [biosimilar] and the reference product will not be greater than the risk of using the reference product without such alternation or switch’.
Both agencies also require immunogenicity be evaluated in comparative studies, which may be done using immunogenicity assays.
The regulatory requirements for Europe and the US highlight the importance of having the right clinical trial design and the right immunogenicity assay for biosimilars.
This article discusses some of the research papers on clinical trial design and immunogenicity assays for biosimilars that have been published during the period of September to December 2012.
Clinical trial design
Biologicals are structurally complex, have complicated manufacturing processes and may cause immunogenicity. All of these considerations mean that biosimilars require class-specific regulatory approval pathways. In line with these considerations, authors Dranitsaris et al. provide a general overview of clinical trial design for biosimilar [1]. They review the regulatory requirements for clinical trials in Europe and the US, as well as reviewing two biosimilars that have recently reported results of randomized trials against brand-name biologicals.
Immunogenicity assays
In order to gain approval for a biosimilar, biosimilarity to the originator drug must be demonstrated. This implies demonstrating the similarity of physical and chemical properties between the biosimilar and its reference product, as well as an evaluation of immunogenicity in comparative studies.
Immunogenicity assays are generally qualitative, and therefore, proving similarity/comparability based on these assays can be a challenge. In a review by authors Cai et al. the challenges of developing and validating immunogenicity assays to support preclinical and clinical comparative studies for biosimilar drug development, as well as the challenges in association with the interpretation of the data are discussed [2].
The research highlights the importance of clinical trial design for biosimilars and the challenges associated with developing and validating immunogenicity assays for comparability studies of biosimilars.
Editor’s comment
Readers interested to learn more about the biosimilarity and interchangeability in the US are invited to visit www.gabi-journal.net to view the following manuscript published in GaBI Journal:
*Professor Shein-Chung Chow is a member of the International Editorial Advisory Board of GaBI Journal, an expert in bioavailability/biosimilarity and bioequivalence; and is the Guest Editor of the educational editorial series on 'Biosimilarity and Interchangeability' currently under production by GaBI Journal, contact us for more information on this educational supplement.
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References
1. Dranitsaris G, Dorward K, Hatzimichael E, Amir E. Clinical trial design in biosimilar drug development. Invest New Drugs. 2013;31(2):479-87.
2. Cai XY, Thomas J, Cullen C, Gouty D. Challenges of developing and validating immunogenicity assays to support comparability studies for biosimilar drug development. Bioanalysis. 2012;4(17):2169-77.
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