Biosimilar Product Development

To assist the sponsor in biosimilar product development, the Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for demonstrating biosimilarity between the proposed biosimilar product and its innovative drug product in terms of safety, purity, and efficacy. This chapter outlines current issues in similarity evaluation that are commonly encountered during biosimilar product development. These issues include, but are not limited to, 90% confidence interval (CI) versus 95% CI, that was then versus this is now (statistical methods for similarity evaluation), alternative methods for analytical similarity evaluation, reference product changes, extrapolation across indications, and sample size requirement. Recent developments in the assessment of interchangeability, detection of reference product change over time, the issue of extrapolation, and the use of non-medical switch are discussed as well.