Session 6: Biosimilars II
Organizer: Lanju Zhang (Abbvie) and Guochen Song (Quintiles)
Chair: Guochen Song (Quintiles)
Lanju Zhang (Abbvie) “How to set up biosimilarity bounds in biosimilar product development”
FDA published three biosimilar guidances in 2012 and one guidance in 2014. With the approval of the first biosimilar product in March 2015, FDA cleared a regulatory pathway for biosimilar product development in US. This calls for stepwise development approach, including analytical biosimilarity, pharmacological biosimilarity and clinical biosimilarity. A tiered approach has been proposed for demonstrating analytical biosimilarity, requiring more statistical rigor with increasing criticality of quality attributes. Specifically, critical quality attributes in tier 1 call for a head to head comparison between reference product and biosimilar product, using a statistical equivalence test to show biosimilarity based on appropriate equivalence bounds. The key is therefore to set up these goalposts. In this talk, we will review some methods to set up equivalence bounds, with a focus on 1.5 times standard deviation of reference product, which was used in the briefing document for the FDA’s first biosimilar product approval. This is a joint work with Sutan Wu from SutanStats.
Thomas Gwise (FDA) “Points to Consider for Biosimilar Clinical Studies”
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) amends the PHS Act and other statutes to create an abbreviated licensure pathway for biological products shown to be biosimilar to an FDA-licensed biological reference product. This presentation will discuss the objectives of the BPCI Act to place into context the role of clinical studies in establishing a product as biosimilar to a reference product. The recent biosimilar application reviewed by FDA’s Oncologic Drug Advisory Committee will serve as an example to explore clinical study design issues particular to biosimilars, including margin determination.
Sujit Ghosh (NC State University and SAMSI) “Dynamic Model Based Methods to Test for Biosimilarity”
In recent years there have been a lot of interest to test for similarity between biological drug products, commonly known as biologics. Biologics are large and complex molecule drugs that are produced by living cells and hence these are sensitive to the environmental changes. In addition, biologics usually induce antibodies which raises the safety and efficacy issues. The manufacturing process is also much more complicated and costly than the small-molecule generic drugs. Because of these complexities and inherent variability of the biologics, the testing paradigm of the traditional generic drugs cannot be directly used to test for biosimilarity. Taking into account some of these concerns we propose a dynamic model based methodology that takes into consideration of the entire time course of the study based a class of flexible models. The empirical results show that the proposed approach is more sensitive than the classical equivalence test approach, and require much less sample size for detecting biosimilarity. [This is a joint work with Dr. Yifang Li, Novartis Inc.]
