Optofluidics Inc. proposes to develop the Excelsior - a high-throughput nanoparticle enumeration and speciation (ID) instrument for QA/QC in protein therapeutics. The need for enhanced sub visible particle compositional characterization in the 0.1 to 10m range is a stated need of the FDA Chemical, Manufacturing and Controls Guidance Division. This is best illustrated in the draft Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products released in February 2013 which states sub visible particulates in the size range of 0.1-10 microns have a strong potential to be immunogenic, but are not precisely monitored by currently employed technologies. The reason for this need is that there is a wealth of data from animal studies and correlative human data that indicate that the presence of ... sub visible particles enhances the immunogenicity of ... protein therapeutics (FDA Office of Biotechnology Products Director Dr. Amy Rosenberg et al, J. Pharmaceutical Sciences, 2012). Our Excelsior Raman ID system works by observing the non-linearly scattered (Raman) light from particles captured in the near-field of an optical waveguide. As we demonstrate in the proposal, this ability to confine particles in the high intensity region of the near-field enables us to collect strong Raman spectra from them while maintaining short enough exposure times to enable throughputs consistent with industrial requirements. We have built a prototype instrument system and demonstrated the feasibility of the near-field Raman ID technique using an assortment of sub-micron particles. Given this, our goals in Phase I are to demonstrate the ability to rapidly ID and enumerate particle/protein aggregate mixtures and to obtain validation data using a sample provided by our industrial collaborators.
We will develop an instrument to address the FDA Chemical, Manufacturing and Controls Guidance Division's stated need for enhanced sub visible particle speciation (ID) in the 100nm to 10m range. Successful development of this instrument will greatly enhance protein drug product development, failure analysis, and quality control capabilities.
