Document text
Principal Investigator: Eric Paul Dixon
Organization: NIGHTHAWK BIOSCIENCES, INC.
Fiscal Year: 2023
Award: $274,649
Funding agency: National Center for Advancing Translational Sciences
PROJECT SUMMARY
To achieve the FDA’s required Sterility Assurance Level for use in humans, pharmaceutical products must
undergo terminal sterilization or aseptic manufacturing. This can be accomplished using physical or chemical
methods such as heat or formaldehyde for simple drug formulations; however, for pharmaceutical products that
have more complex drug formulations or that contain biologically active material important for downstream
applications (cell-containing therapeutics, vaccines, etc.), gamma irradiation is the preferred method of
sterilization. Gamma irradiation destroys nucleic acids to inactivate pathogens or render any cells replication
incompetent but leaves structural components like proteins intact. The logistical challenges of reliance on gamma
irradiation for terminal sterilization are, however, significant. Gamma irradiation requires high doses of radiation,
necessitating significant regulatory restrictions and specialized infrastructure, driving up costs and processing
times to manufacture a finished drug. As such, few biomedical research and production facilities are able to
adopt gamma-irradiation processes in-house to expedite manufacturing timelines, and they remain reliant on
centralized shielded facilities. Low energy electron irradiation (LEEI) represents a practical and inexpensive
alternative to gamma irradiation; however, a low penetration depth limits its utility for liquid suspensions. To
overcome these obstacles, Heat Biologics has partnered with Georgia Institute of Technology and Texas A&M
University to develop a microfluidics-enabled in-line continuous process for high-throughput LEEI sterilization of
pharmaceuticals. This strategy uses microfluidic manifolds to bring a continuously flowing product into the
working depth of an LEEI beam at a sufficient volumetric flow rate to allow for scaling to commercial capacity.
Since the product is terminally sterilized by this process, it enables end-to-end control as an alternative to
centralized sterilization at a shielded facility. In preliminary studies, rapid prototyping resulted in the design of a
consumable chip manifold. Computational modeling followed by experimental validation of the microfluidic chip
design demonstrated flow uniformity and good e-beam penetration through the channels without compromising
biological material. In this Phase I STTR project, this interdisciplinary team will finalize the microfluidics design
and test the prototype system in two pharmaceutical cell therapy products to confirm inactivation efficiency and
active agent bioavailability following irradiation. A consumable commercial set will be built to achieve 30L/hour
processing to ensure that the system can be appropriately scaled to accommodate commercial scale production.
Completion of these objectives will validate a high-throughput microfluidics device that when combined with e-
beam irradiation will provide standard biological research and production laboratories with the ability to produce
and irradiate biologically active pharmaceutical products at the site of manufacture.
Terms: <Adhesives><Adopted><Al element><Aluminum><Assay><Automobile Driving><Bacteria><Bioassay><Bioavailability><Biocompatible Materials><Biologic Assays><Biologic Products><Biological><Biological Agent><Biological Assay><Biological Availability><Biological Products><Biomaterials><Biomedical Research><Cell Body><Cell Line><Cell Therapy><CellLine><Cells><Chemicals><Complex><Computer Models><Computerized Models><Devices><Dimensions><Dose><Drug Formulations><Drugs><ELISA><Electron Beam><Enzyme-Linked Immunosorbent Assay><Failure><Filamentous Fungi><Filtration><Filtration Fractionation><Formaldehyde><Formic Aldehyde><Gamma Radiation><Gamma Rays><Hour><Human><Infrastructure><Injections><Laboratories><Lead><Liquid substance><Maps><Medical Device><Medication><Metals><Methods><Methyl Aldehyde><Micelles><Microfluidic Device><Microfluidic Lab-On-A-Chip><Microfluidic Microchips><Microfluidics><Modern Man><Molds><Nucleic Acids><Oxomethane><Pb element><Penetration><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Physiologic Availability><Polymers><Procedures><Process><Product Packaging><Production><Proteins><Radiation><Radiation Dose><Radiation Dose Unit><STTR><Sampling><Site><Small Business Technology Transfer Research><Solvents><Sterility><Sterilization><Strains Cell Lines><Surface><Suspension substance><Suspensions><System><Technology><Testing><Texas><Therapeutic><Thick><Thickness><UHMWPE><UHMWPE polyethylene><Universities><Vaccines><Validation><Virus><biologic><biological material><biological research><biologics><biopharmaceutical><biotherapeutic agent><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><computational modeling><computational models><computer based models><computerized modeling><cost><cultured cell line><design><designing><dosage><driving><drug/agent><electron energy><enzyme linked immunoassay><fluid><gamma irradiation><heavy metal Pb><heavy metal lead><innovate><innovation><innovative><instrument><ionization><irradiation><lipid based nanoparticle><lipid nanoparticle><liquid><manufacture><manufacturing process><meter><microfluidic chip><microfluidic technology><multidisciplinary><nano particle><nano-sized particle><nanoparticle><nanosized particle><particle><pathogen><pharmaceutical><polyetheretherketone><polymer><polymeric><preservation><pressure><prototype><simulation><sterile><technology platform><technology system><therapeutic vaccine><thermal stress><thermo stress><timeline><tool><treatment vaccines><ultra-high MW polyethylene><ultra-high molecular weight polyethylene><vaccine for the treatment><vaccine for treatment><validations><µfluidic><µfluidic technology><γ-Radiation><γ-Ray><γ-irradiation>