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Clinical development, immunogenicity, and interchangeability of follow-on complex drugs

22 Jan 2014

Abstract: 
Although not derived from living sources, non-biologic complex drug (NBCD) products have the immunogenicity and molecular complexity of biologic drugs. NBCD typically contain heterogenous mixtures of closely related nanoparticulate components that cannot be isolated, quantified, or entirely characterized physicochemically. Development of follow-on versions of NBCD poses many of the same scientific challenges associated with biosimilar drugs. Like biologics, the manufacturing methods used by the innovator to produce NBCDs ensure their identity, and consistent quality and activity. Some variation in alternate-sourced products is inevitable. Because of their complexity and because biological activity is often not correlated with serum pharmacokinetics, follow-on NBCDs can be shown to be similar, but not identical, to the originator product. Even slight variations in a follow-on NBCD can increase the risk of unwanted immunogenicity, safety problems, and/or reduced therapeutic effects. Issues related to follow-on versions of liposomal formulations, iron–carbohydrate complexes, and glatiramoids are described here to illustrate aspects of NBCDs that render the abbreviated pathway for approval of small-molecule drugs unsuitable for follow-on NBCDs.  The US Food and Drug Administration has made “equivalence of complex drugs” a Generic Drug User Fee Amendment priority initiative for fiscal year 2014. Experience suggests the same enhanced pre-approval scrutiny of biosimilar drugs should be applied to follow-on NBCDs. Preclinical and/or clinical data may be required to establish similar quality, immunogenicity, safety, and efficacy between a follow-on NBCD and a reference drug, and automatic switching or substitution of a follow-on NBCD for the originator should be contingent on demonstration of therapeutic equivalence.

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Date: 
22 January 2014

Click here to view the full article which appeared in Generics and Biosimilars Initiative Journal