Using morphologically-directed Raman spectroscopy (MDRS) for generic nasal spray development.
Q:Last year, the FDA published an article titled “The FDA Embraces Emerging Technology for Bioequivalence Evaluation of Locally Acting Nasal Sprays” in which the FDA’s Bing Li said that the agency was very happy to have accepted MDRS data in lieu of a clinical endpoint BE study. Can you explain what happened?
A:The FDA accepted in vitro data measured using MDRS in place of data from a clinical endpoint bioequivalence (BE) study for an Abbreviated New Drug Application (ANDA) submitted by Apotex for a mometasone furoate nasal spray. Using MDRS, the applicant was able to compare the size, shape, and chemical form of the active pharmaceutical ingredient (API) in the test and reference listed drug (RLD) formulations. These data were used to support the claim that the test product would behave comparably when acting locally within the nasal cavity and consequently demonstrate BE.
MDRS combines image-based particle size and shape measurements with Raman spectroscopy in order to generate component-specific particle size and shape data for the individual populations within a formulation, including the API. In the specific case of suspension nasal sprays such as this mometasone furoate product, the FDA recognized that MDRS is a robust and efficient technique for measuring the particle size and shape of the API, pre- and post-actuation.
The FDA had previously rejected clinical endpoint BE study data that were submitted with the original ANDA because the API used to conduct the study was manufactured at a site other than the one intended for commercial API manufacture. In addition, clinical endpoint BE studies are particularly challenging for locally-acting drug products because efficacy is independent of systemic absorption, making conventional pharmacokinetic (PK) study data less relevant.