Characterization of nanoparticles and biologics is a critical step in the development of important new pharmaceutical therapeutics as, in many cases, preclinical characterization is the rate-limiting phase of the commercialization process. Nanoparticle therapeutics poses unique challenges for characterization that require an interdisciplinary approach in which several orthogonal methods are required to provide a complete picture. Cryo-electron microscopy, with its unique capability for providing exact visual information of size, shape, morphology, and aggregation of a sample in its natural hydrated state, is a powerful additional tool in the armamentarium of characterization techniques applied to nanoparticles. NanoImaging Services, Inc. was established in 2007 in order to provide cryoEM imaging services specifically focused on the characterization of biologics and nanoparticles. Over the past 18 months it has become clear that there is a critical need for more quantitative analysis of multiple cryoEM images. The images must be processed, analyzed and evaluated with the goal of providing numerical data that can be used for assessing the characteristics of the samples and comparing these characteristics to the results obtained from other orthogonal methods. Quantitation is critical for assessing lot-to-lot comparisons, quality assurance and control, monitoring samples over time, and when providing data to the regulatory agencies. Here we request support to undertake a 6 month study to determine the feasibility of developing several quantitative characterization protocols that are designed to address specific needs in the research and development of new biologics and nanoparticles as therapeutics. Specifically we will develop quantitative tools to characterize particle morphology and aggregation state and test and validate the methods using a number of samples of high interest as pharmaceutical therapeutics.
Arguably two of the fastest growing sectors of the biopharmaceutical industry are the production of biologics as therapeutic agents and nanoparticles as drug delivery vehicles. There is considerable evidence that the physical properties of biologics and nanoparticles is tightly linked to their functional behavior and may thus be a determining factor in the biodistribution, safety, and efficacy of the pharmaceutical product. Cryo- electron microscopy, with its unique potential for providing quantitative information of size, shape, morphology, and aggregation of a sample in its natural hydrated state, is a powerful additional tool in the armamentarium of characterization techniques applied to nanoparticles.