This was the first time that the Office of Generic Drugs accepted in vitro data in place of a clinical endpoint study to demonstrate bioequivalence of a generic nasal spray, and the approval sets a precedent for future submissions. The potential elimination of the requirement for clinical studies via this strategy is of substantial interest and benefit to the industry since such studies are both time-consuming and costly.
Q: How does component-specific data help to define the performance of locally-acting nasal sprays?
A: For a locally-acting nasal spray, BE depends on ensuring that deposition of the dose in the nasal passages is comparable with the test and reference products. The FDA’s draft product specific guidance for mometasone furoate metered nasal sprays, for example, calls for laser diffraction droplet size distribution measurement to help ensure analogous deposition behavior, but analyzing droplet size alone is insufficient. It is necessary to verify that the delivered API particles of the test product are the same size, shape and in the same state of dispersion as those of the RLD to demonstrate that the dissolution rate of the API, and consequently its bioavailability at the site of action, is likely to be equivalent.
Q: How does MDRS work? What advantages does it offer relative to other techniques that may be applied to try to access the same information?
A: MDRS combines automated imaging to gather data for morphological characterization and direction with Raman spectroscopy for chemical identification. Automated imaging makes it possible to gather individual images of tens of thousands of particles in just a few minutes, and the system uses parameters determined from these images to build up statistically significant particle size and shape distributions.
The user can then utilize these data to identify specific populations within the sample for chemical identification. For example, the user could choose to apply Raman spectroscopy to all particles less than 7 μm in size that are close to being completely spherical or, alternatively, focus attention on larger, irregularly-shaped particles to study agglomerates.
In this way, through classification on the basis of particle size and shape, and the elective application of Raman spectroscopy to specific particles, MDRS generates morphological information for specific populations within a sample/formulation.
