Microfluidic technology platform as a continuous end-line process to inactivate pharmaceuticals - 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.
