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Demonstrating Q3 Structural Equivalence of Nasal Sprays: New Analytical Concepts and Techniques

Suman JD, Olkhovyk O.

RDD Asia 2018. Volume , 2018: 15-26.

Abstract:

Demonstrating in vivo bioequivalence (BE) in complex dosage forms such as suspension-based nasal sprays is challenging. One reason for this is due to the lack of validated particle size methodologies to determine not only the size of the active ingredients but also the extent of agglomeration, which can impact bioavailability. To facilitate bioequivalence determinations, the United States Food and Drug Administration (FDA) Generic Drug User Fee Amendments (GDUFA) has supported research to advance the concept and underlying science of Q3 equivalence to compare innovator and generic drug products. Q3 equivalence is defined as the same components in the same concentration with the same arrangement of matter. The spatial arrangement of particles and agglomerates can now be quantified by objective, chemically-specific methods such as Raman spectroscopy and scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM-EDS). Used alone or as orthogonal methods, these techniques can be validated to quantify < 2 μm particles. With this information, pharmaceutical companies can de-risk clinical studies by understanding their product attributes. In addition, chemically-specific particle size methods can be used in a regulatory setting to apply for clinical biowaivers or as indicators of in vitro  BE.