Vaccines are often developed in freeze-dried (lyophilized) presentations due to requirements on stability, shipping, and faster timelines in early clinical development. The current lyophilization technology is capital and energy-intensive, largely due to the use of indirect, conductive heat exchange. The heat removal and input in freezing, primary and secondary drying are via contact between the product and shelves cooled or heated by a circulating working fluid such as silicone oil. This is slow, inefficient, and leads to non-uniform freezing and drying, especially in large-scale production systems. The use of the same heat transfer method for both freezing stage at atmospheric pressure and drying in vacuum is largely inefficient as it does not exploit the distinct mechanisms for the liquid, frozen, and partially dried porous material. Poor heat transfer, especially for the product in pre-filled double-chamber syringes is the rate and cost limiting bottleneck for manufacturing lyophilized biologics.
This project advances the tunable RF/MW drying in application to vaccine manufacturing. Tunable RF/Microwave Drying is a technology invented at Purdue which uses EM sources with variable frequency for optimizing power absorption by the frozen or liquid product in realistic complex enclosures. It applies statistical electromagnetics to provide average-power distribution that is uniform to a specified standard deviation. This is key to achieving uniformity of residual moisture and reconstitution time. The proof-of-concept experiments using Gen1 RF/MW system retrofitted to a lab-scale lyophilizer demonstrated x2 faster drying than the conventional lyophilization for protein formulations while achieving a comparable or lower residual moisture. The use of solid-state tunable MW sources and EM mixing allows drying at about an order of magnitude lower power input per product volume as compared with the magnetron-based MW heating.
The development of tunable RF/Microwave lyophilization technology significantly impacted the field of vaccine and biopharmaceutical manufacturing. Traditional lyophilization methods, which rely on indirect, conductive heat exchange, are capital- and energy-intensive, often resulting in inefficient and non-uniform freezing and drying, particularly in large-scale production. By introducing tunable RF/Microwave heating, this project advanced the discipline by offering a more efficient method that uses variable frequency electromagnetic sources to optimize power absorption during the lyophilization process.
This innovation enables faster drying times, accelerating the manufacturing process by 2-5 times compared to conventional batch-mode systems.
The impact is profound, as it not only increases manufacturing throughput but also reduces costs and improves the stability and quality of vaccines and biopharmaceuticals, ultimately leading to faster, safer, and more cost-effective delivery of medication to patients.
This project demonstrated a tunable RF/MW lyophilization unit with closed‑loop control that accelerates primary drying for drug companies, resulting in time benefits across vaccine lyophilization.
Fully functional lab scale freeze drying qRF heating unit with closed loop capable of speeding up primary drying time by 2-5 times.
Stability data for 2 types of pharmaceutically relevant products that indicate no significant impact from RF drying on critical product quality attributes
Process model with tuned parameters capable of predicting temperatures and drying time for a range of conditions.
Pilot scale first generation qRF design that meets stringent regulatory requirements and offers flexibility to conduct conventional freeze drying cycles, enabling comprehensive evaluation and comparison of product quality attributes
Darwish, A., Strongrich, A. D., Alexeenko, A., & Peroulis, D. (2024). Optimizing Statistical Field Uniformity for RF Heating in Lyophilization: Modeling and Experimental Validation. IEEE Transactions on Instrumentation and Measurement, 73, 1-9. https://doi.org/10.1109/TIM.2024.3381275
Mutukuri, T. T., Darwish, A., Strongrich, A. D., Peroulis, D., Alexeenko, A., & Zhou, Q. T. (2023). Radio Frequency – Assisted Ultrasonic Spray Freeze Drying for Pharmaceutical Protein Solids. Journal of Pharmaceutical Sciences, 112(1), 40-50. https://doi.org/10.1016/j.xphs.2022.09.024
Alexeenko, A., Darwish, A., Peroulis, D., Strongrich, A., Kazarin, P., wheeler, I., munson, E., Patil, C., Tower, C., Zhou, Q., Narsimhan, V., Yoon, K., Stanbro, J., Renawala, H., Roth, D., DeMarco, F., & Griffiths, J., Tunable RF/Microwave Lyophilization of Biologics with Closed-Loop Control, NIIMBL National Meeting, Washington, DC, June 27, 2023.
Alexeenko, A., Strongrich, A., Darwish, A., & Peroulis, D., Microwave Assisted Freeze Drying, NIPTE Advanced Manufacturing Technologies: Accelerating Injectable Product Development and Addressing Drug Shortages Workshop, Washington, DC, January 9, 2024.
Darwish, A., Strongrich, A., Peroulis, D., & Alexeenko, A., Tunable RF/Microwave Lyophilization of Biologics: From Modeling to Experimental Validation, Freeze Dry Conference, Breckenridge, CO, August 1, 2023.
Wheeler, I., Alexeenko, A., & Narsimhan, V., Modeling and PAT for Microwave-Driven Lyophilization, International Society of Lyophilization – Freeze Drying 2024 International Meeting, Torino, Italy, May 6, 2024.
Wheeler, I., Alexeenko, A., & Narsimhan, V., Modeling and PAT for Microwave-Driven Lyophilization, International Society of Lyophilization – Freeze Drying Midwest Conference, Chicago, IL, April 18, 2024.
Alexeenko, A. & Strongrich, A., Microwave Freeze Drying for Biologics Seminar at FDA, Federal Food and Drug Administration, Silver Springs, MD, October 17, 2023.
Alexeenko, A. & Strongrich, A., Microwave Freeze Drying for Biologics Seminar at NIST, National Institute of Standards and Technology on invitation from Division 644, Gaithersburg, MD, October 18, 2023.
Alexeenko, A., RF/Microwave Lyophilization of Biologics, 2022 NIPTE Research Conference, Virtual, November 29, 2022.
Darwish, A., Strongrich, A., Alexeenko, A., & Peroulis, D., Tunable Quasi Random-Field Microwave-Assisted Freeze Drying: A Novel Method for Optimizing Pharmaceutical Lyophilization, 2024 IEEE INC-USNC-URSI Radio Science Meeting (Joint with AP-S Symposium), Florence, Italy, July 24, 2024.
Peroulis, D., Tunable RF/Microwave Freeze Drying for Biologics, International Society of Lyophilization-Freeze Dry, Chicago, IL, April 20, 2023.
Strongrich, A., Beyond Late-night Leftovers: High Frequency Microwave Heating Applications In Pharmaceutical Freeze Drying, International Society of Lyophlization-Freeze Dry, Europe, Torino, Italy, May 8, 2024.
Strongrich, A., Darwish, A., Alexeenko, A., & Peroulis, D., Beyond Late-night Leftovers: High Frequency Microwave Heating Applications In Pharmaceutical Freeze Drying, Beyond Late-Night Leftovers: High Frequency Microwave Heating Applications in Pharmaceutical Freeze Drying, Bethesda, MD, March 6, 2024.
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Purdue University
IMA Life North America Inc.
Merck Sharp & Dohme LLC
