Application of the parallel line assay to assessment of biosimilar products based on binary endpoints.
Biological drug products are therapeutic moieties manufactured by a living system or organisms. These are important life-saving drug products for patients with unmet medical needs. Because of expensive cost, only a few patients have access to life-saving biological products. Most of the early biological products will lose their patent in the next few years. This provides the opportunity for generic versions of the biological products, referred to as biosimilar drug products. The US Biologic Price Competition and Innovation Act passed in 2009 and the draft guidance issued in 2012 provide an approval pathway for biological products shown to be biosimilar to, or interchangeable with, a Food and Drug Administration-licensed reference biological product. Hence, cost reduction and affordability of the biosimilar products to the average patients may become possible. However, the complexity and heterogeneity of the molecular structures, complicated manufacturing processes, different analytical methods, and possibility of severe immunogenicity reactions make evaluation of equivalence between the biosimilar products and their corresponding reference product a great challenge for statisticians and regulatory agencies. To accommodate the stepwise approach and totality of evidence, we propose to apply a parallel assay to evaluate the extrapolation of the similarity in product characteristics such as doses or pharmacokinetic responses to the similarity in binary efficacy endpoints. We also report the results of simulation studies to evaluate the performance, in terms of size and power, of our proposed methods. We present numerical examples to illustrate the suggested procedures.
Clinical Informatics and Medical Statistics Research Center and Graduate Institute of Clinical Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Jr-Rung
JR
Lin
Shein-Chung
SC
Chow
Chih-Hsi
CH
Chang
Ya-Ching
YC
Lin
Jen-pei
JP
Liu
D000465:Algorithms; D001688:Biological Products; D059451:Biosimilar Pharmaceuticals; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D017277:Drug Approval / Q000379:methods*; D004341:Drug Evaluation / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
D001688:Biological Products; D059451:Biosimilar Pharmaceuticals