LAUSR

Research on assessing similarity between two biologics has received much attention in recent years, as the biologics patent cliff began in the US drug market in 2012 (Calo-Fernández andMartínez-Hurtado, 2012). The Biologics Price Completion and Innovation (BPCI) Act was written into law on 23 March 2010, and in this act, a biosimilar was defined as a product that is highly similar to the reference product, notwithstanding minor differences in clinically inactive components and the presence of no clinically meaningful differences in terms of safety, purity, and potency. To regulate biosimilar submissions and implement the BPCI Act, in April 2015 the US Food and Drug Administration (FDA) published the first official biosimilar guidance for industry, entitled “Scientific considerations in demonstrating biosimilarity to a reference product.” This guidance contains three main topics: (1) a stepwise approach to demonstrate biosimilarity; (2) a totality-of-the-evidence approach to assess biosimilarity; and (3) general scientific principles in conducting comparative analyses of biosimilar trials. There are three other pieces of guidance published in the same year focusing on the quality control and answers to questions from sponsors. In addition, in January 2017 the FDA published another draft guidance entitled “Considerations in demonstrating interchangeability with a reference product guidance for industry” to assist sponsors in demonstrating that a proposed product is interchangeable with its reference product. In this special issue, we invited statisticians from federal agency, academia, and industry to share their current thinking about biosimilarity assessment. Topics cover analytical similarity assessment, sample size requirement, drug interchangeability, and some statistical considerations on biosimilar trials. This special issue begins with three articles on the topic of analytical similarity assessment contributed by the authors from the US FDA Center of Drug Evaluation and Research (CDER) and academia. In order to evaluate the analytical similarity between a biosimilar product and its reference product, a working group from the US FDAproposed a three-tier approach. The first article by Tsong et al. from the FDA CDER gives a detailed discussion on the Tier 1 equivalence test and it is followed by Wang and Chow’s paper on equivalence acceptance criteria in analytical similarity assessment. Next Shen et al. gave some statistical considerations regarding correlated lots in the analytical biosimilar equivalence test. The following four articles are related to sample size requirements for conducting equivalence trials. Since imbalanced sample size may be common in biosimilar product development, Dong et al. showed that sample size imbalance can lead to higher power for less similar products. The next article by Chow et al. provides statistical justification to the previous article and presents an alternative method for the sample size requirement for a Tier 1 equivalence test. Two other topics related to sample size requirement follow. Chang et al. give the sample size requirement for three-arm equivalence trials with discrete endpoints, Poisson or negative binomial response, while Shen and Machado focused on the bioequivalence evaluation of sparse sampling pharmacokinetics data using the bootstrap resampling method. The following four articles deal with drug interchangeability. The first article by Chow et al. gives a hybrid parallelcrossover design for assessing drug interchangeability of biosimilar products. Next, Chen and Chow proposed a reversed average bioequivalence criterion under a 2 × 4 replicated crossover design. Another paper by Li and Chow provides discussions on the topic of a scaled criterion for drug interchangeability. Zheng et al. gave their thoughts on the safety margin for drug interchangeability. The next two articles present tests that can be applied for equivalence assessment: (1) Wald’s test for variance-adjusted