CERSI P.I. and Collaborator: Taylor Woehl, Ph.D., UMCP Department of Chemical and Biomolecular Engineering
FDA SMEs and Collaborators: Bin Qin, Ph.D., CDER FDA, Yan Wang, Ph.D., CDER FDA, Stephanie Choi, Ph.D., CDER, FDA
Regulatory Science Challenge
Nanoparticle based drugs are drug formulations where the active drug substance is formulated into nanoparticles with sizes in the range of 100 – 1000 nanometers. These unique drugs have been found in several cases to be significantly more affective cancer therapeutics compared to conventional small molecule drugs. However, nanoparticles adopt a broad range of particle sizes and characteristic due to the larger number of drug molecules per nanoparticle. This contrasts small molecule and protein drugs, where all drug molecules are identical copies of each other. The size distribution of nanoparticle drugs determines how they interact with biological tissue and thus nanoparticle size is a critical quality attribute of these drugs that must be characterized as part of the FDA chemistry review. Characterizing particle size distribution is particularly important for generic nanoparticle drug FDA applications, where applicants should demonstrate their drug is highly similar to the originator drug. Conventional optical microscopy methods are not capable of accurately measuring the size distribution of nanoparticle drugs, making it difficult to establish similarity of a generic drug to an originator. New optical microscopy tools must be developed to characterize generic nanoparticle drugs.
Project Description and Goals
This project will develop a new analytical tool, hyperspectral interferometric scattering microscopy (h-IFS), to characterize the size distribution of nanoparticle drugs. This approach uses a simple optical microscopy method together with microfabricated sensors to measure the size of nanoparticles based on how they scatter light. Researchers at University of Maryland will build a prototype instrument and will develop complex image analysis software to process characterization data. Researcher will use well-characterized model nanoparticle samples to validate the method and determine its limitations and strengths. Researchers will demonstrate application of this method to characterize two FDA approved nanoparticle drugs for metastatic cancer, Abraxane and Onivyde. Given that particle size is a critical quality attribute of nanoparticle drugs, this project will provide a powerful new characterization tool for generic nanoparticle drug developers. Measurements of particle size by h-IFS will help FDA reviewers make more informed decisions on the approval of generic nanoparticle drugs.