Considerations on species selection in non-clinical similarity assessment of biosimilars:an example of post-approval change of an infliximab biosimilar
Monoclonal antibody biosimilar is currently a hot topic in drug development.According to the principle of step-by-step comparison,non-clinical studies serve as an effective method to bridge the gap between CMC and clinical trials.Non-clinical studies also play a crucial role in assessing pharmaceutical similarity during post-marketing changes.For antibody drugs without relevant animal species/models,innovative drugs can undergo non-clinical evaluations using methods such as transgenic models or surrogate molecules.Unlike innovative drugs,the development or post-marketing changes of biosimilars can employ non-target-mediated studies conducted in unrelated species,providing in vivo evidence for similarity assessment.For the biosimilar of infliximab,which cannot be compared non-clinically using related species,non-clinical comparative assessments have been conducted using rat or transgenic mouse models for the approved marketed products.After the commercialization of the injectable infliximab product(CMAB008),a significant process change was made.Based on CMC comparisons,non-clinical comparative assessments were conducted using rat models.By comparing the main exposure parameters(Cmax,AUC0-t,AUC0-∞)and immunogenicity,the similarity of the product before and after the change was further demonstrated.Through this case of non-target-mediated non-clinical comparative assessment,it helps to understand the PK characteristics of antibody drugs with unrelated species as viable options,providing reference for other similarity evaluation studies.
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