SBIR-STTR Award

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 10µm 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 This is best illustrated in the draft Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products released in February 2013 which states "sub visible particulates in the size range of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.

Public Health Relevance Statement:


Public Health Relevance:
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 10µm range. Successful development of this instrument will greatly enhance protein drug product development, failure analysis, and quality control capabilities.

Project Terms:
No Project Terms available

Optofluidics Inc. proposes to develop FlowID, a particle analysis quality control method designed to identify unwanted particles in therapeutic proteins that are injected directly into patients. Protein therapeutics currently represent between 15 and 30% of the overall pharmaceutical market. The primary concern for this class of therapeutics is that they can elicit an immune response from patients who develop anti-drug antibodies. The drug’s effect is therefore eliminated between 1 and 10 percent of patients who return to their original disease state. The presence of particulate matter in these therapeutics (e.g. shed glass from a syringe or a protein aggregate) can enhance this immune response and, due to the patient safety risk the FDA regulates the amount of particles that can be present. There are always some number of particles in each injected sample, and although their presence can be detected, they don’t know what the particles actually are. A QC tool that can identity the particles would help manufactures trace them back to their source (e.g. a bad lot of syringes) and eliminate them. The proposed FlowID technology will provide high throughput particle identification that is an order of magnitude faster than the existing systems. In addition, it will provide particle counting information on par with state-of-the art instrumentation. The heart of the innovation is in novel flow cell chips with a lithographically defined grid of micropores. It uses a combination of automated microscope imaging with FTIR spectroscopy to quantitatively count, size and identify each particle. It will be an order of magnitude faster than the state of the art, and completely automated. We believe that the additional typing capability of a routine particle counting instrument will speed up clinical development and enable higher quality, safer therapeutics. At the conclusion of this Phase II effort we will have developed a beta instrument and consumables and conducted testing on-site at GSK.

Public Health Relevance Statement:
Narrative In this work Optofluidics will develop a new quality control instrument that can rapidly identify the presence of unwanted particulates in pharmaceutical injectable drugs. The presence of these particles contributes to a side effect where patient’s bodies reject the drug. This returns them to their original diseased state and is a serious health risk and an obstacle in the development of these therapeutics. A successful project will contribute to the health and safety of patients receiving these medications.

Project Terms:
No Project Terms avail