Statistical Designs for Assessing Interchangeability of Biosimilar Products

Zhang Zz Chow Sc

doi:10.4172/2169-0138.1000109

Abstract

More and more biopharmaceutical and/or biotech companies begin to concern regulatory approval of biosimilar products, due to some innovator products will expire in decades. Once more biological products are going off patient, the problem whether approving biosimilar products used interchangeably and safely will be considered. Using a biological product of the reference product interchangeably, the United States Food and Drug Administration (FDA) requires that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product, is not greater than the risk of using the reference product without such alternation or switch. For this purpose, based on the concept of switching and/or alternation several useful designs for assessing drug interchangeability are proposed. In addition, by developed biosimilarity index, a uni?ed approach is discussed. The proposed method is robust against biosimilarity criteria and is applicable under a valid and appropriate study design.

Highlights

When the patent of the brand-name drug product expires, generic companies and/or bio- pharmaceutical have to file an Abbreviated New Drug Application (ANDA) for generic approval
For a given criterion for biosimilarity and a valid study design, the biosimilarity index in a given functional area or domain will be given by the following steps [7]: Step 1: Assess the average biosimilarity based on a given criterion, e.g. (80%, 125%) based on log-transformed data; Step 2: Calculate the local biosimilarity index based on the observed ratio and variability; Step 3: Claim local biosimilarity if the 95% confidence lower bound of p is larger than a pre-specified number p0, where p0 can be obtained based on an estimate of reproducibility probability for a study of comparing a reference product to itself, i.e., an R−R study
Under the appropriate study designs, we propose the switching index and alternating index to assess the switching and alternating, it is same to biosimilarity index for assessment of biosimilarity

Summary

Introduction

When the patent of the brand-name drug product expires, generic companies and/or bio- pharmaceutical have to file an Abbreviated New Drug Application (ANDA) for generic approval. In terms of safety or diminished efficacy, an appropriate study design should be chosen to address (i) the risk of alternating or switching between the uses of the generic product and the innovative product, (ii) the risk of using the reference product without alternation or switching, and (iii) the relative risk between switching/alternating and without switching/alternating. Note that for analysis of data collected from a two-sequence dual design, the statistical methods, including the evaluation of average biosimilarity, the estimates of intra-subject variabilities and inference on carry-over effect, are given in Chow and Liu [1], at the same time they have discussed the expected values of the sequence-by-period means, analysis of variance table. This new criterion is currently being studied by Endrenyi et al [12]

Statistical Methods

Concluding Remarks