Keywords: biosimilars, PK Similarity, scaling approaches
Assessment of pharmacokinetic (PK) similarity is part of the comparison of two potentially biosimilar biologics. It is sometimes suggested that we should use the regulatory structure currently in place for bioequivalence (BE) assessment of small molecule drugs to assess PK similarity of biologics. In the case of small molecule BE, the appropriate equivalence margin may depend on the underlying variability, particularly within-subject variability, of the Reference drug. The Center takes such variability into account in setting a BE margin for the cases of highly variable drug products and narrow therapeutic index drug products, conceptually scaling the allowable difference between products to the underlying variability, which must itself be estimated from the results of the BE study. Might such scaling methods be applicable to PK similarity assessment for biosimilars? If appropriate, such methods may obviate the need for large sample sizes in PK similarity studies. Also, there is no reason why such scaling methods could not be implemented within an appropriately validated adaptive experimental design, such as a sample size reestimation design.