LyoHUB Projects

Advanced Characterization and Manufacturing Methods for mRNA Vaccine Development

Funded by: NIIMBL (National Institute for Innovation in Manufacturing Biopharmaceuticals) as part of the American Rescue Plan Completed in 2023

Investigators: Eric Munson (PI, Purdue IMPH), Alina Alexeenko (Co-PI, Purdue ChemE/AAE), Elizabeth Topp (Co-PI, Purdue IMPH), Tony Zhou (Co-PI, Purdue IMPH)

Current mRNA/LNP vaccines are solutions which must be stored at -80 °c to remain stable. refrigeration accounts for a large portion of the costs associated with vaccine shipment and storage. in this project, formulation and manufacturing methods for solid room-temperature stable vaccines were explored.

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Random Field Radio Frequency Lyophilization

Investigators: Alina Alexeenko (PI, Purdue), Ahmad Darwish (Purdue), Drew Strongrich (Purdue), Petr Kazarin (IMA Life), Chanakya Patil (Purdue), Cole Tower (Purdue), Isaac Wheeler (Purdue), Eric Munson (Co-PI, Purdue), Qi Zhou (Co-PI, Purdue), Vivek Narsimhan (Co-PI, Purdue), Kyu Yoon (Purdue), Steven L. Nail (Consultant), Anthony Cofer (Purdue), Justin Stanbro (IMA Life), Harshil Renawala (Merck), Daniel Roth (Merck), Francis DeMarco (IMA Life), Justin Griffiths (IMA Life), and Dimitrios Peroulis (Co-PI, Purdue)

There has recently been a surge in the demand for lyophilized injectable products. The rapidly expanding portfolio of new biologics, particularly in the aftermath of the COVID-19 pandemic, highlighted the challenges associated with freeze-drying since such a process is very time-consuming, taking anywhere from days to weeks. Toward that end, this random field radio frequency lyophilization system addresses these shortcomings by applying highly controllable volumetric heating capable of accelerating freeze-drying processes

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Simulating Sublimation Front Shapes in Microwave-Assisted Freeze Drying

Investigators: Isaac Wheeler (Purdue ChemE Ph.D. student), Alina Alexeenko (PI, Purdue), Dimitrios Peroulis (Purdue Electrical and Computer Engineering), Ahmad Darwish (Purdue Electrical and Computer Engineering), Vivek Narsimhan (Purdue ChemE), Drew Strongrich (Purdue LyoHUB), and Petr Kazarin (Purdue AAE, now at IMA Life)

Microwave-assisted freeze drying is an exciting new method of accelerating the primary drying stage of lyophilization. One advantage of the technology is the ability to bypass the container and heat the frozen product directly, since electromagnetic heating is applied throughout the chamber volume (rather than from a surface, e.g. the top of a shelf). However, as everyday experience with microwave ovens would suggest, glass vials and similar containers may also be heated by the microwave field. 

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Empirical Correlation for Predicting Equilibrium Moisture Content in Sugar/Protein Mixtures During Freeze-Drying

Investigators: Kyu Yoon (Purdue ChemE Research Scientist) and Vivek Narsimhan (Purdue ChemE)

Predicting the equilibrium moisture content of a dried cake during freeze-drying is essential for understanding the desorption kinetics of bound water and ensuring the final product’s quality and stability. The weighted-average model is frequently used for mixture formulations; however, this correlation often falls short in complex systems, such as sugar/protein mixtures, due tointeractions between sugar and water monolayer sites on dried proteins.

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Mechanical Characteristics of Vial Strain During Freezing and Thawing Operations Using Amorphous Excipients

Investigators: Ian Flynn (Purdue LyoHUB), Drew Strongrich (Purdue LyoHUB), Serguei Tchessalov (Pfizer), Bakul Bhatnagar (Pfizer), and Evgenyi Shalaev (Abbvie)

Wireless strain sensors developed in LyoHUB are being evaluated for their unique ability to detect mechanical stresses and strains in primary packaging during freezing, thawing, and freeze drying. Prior research in the LyoHUB Demonstration Facility has identified key differences in strain response for amorphous excipients such as sucrose and trehalose at different concentrations. For example, the temperature and strain profiles of sucrose at concentrations from 5-80% are shown in Figure 1. Recent studies are focused on leveraging computational modeling to understand the implication of these differences in strain behavior.

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Experimental Study of Freezing-Induced Concentration Gradients in a Container

Investigators: Marilyn Padua (Purdue PMP student), Sai Bhusurapalli (Purdue PMP student), Jie Wang (AbbVie), Sherwin Shang (AbbVie), Kyu Yoon (Purdue ChemE Research Scientist), and Vivek Narsimhan (Purdue ChemE)

Freezing is currently a common unit operation in the production and storage of biopharmaceuticals. Although biopharma- ceuticals are preferentially stored in the frozen state, degradation due to aggregation, protein unfolding, air bubbles formed on the ice crystallization front, and local pressure and mechanical stresses due to volume expansion during water-to-ice transformation, complications may affect the stability of frozen biopharmaceuticals. The stability of frozen biologicals may also depend on the sample size due to its impact on the freezing kinetics, cryoconcentration effects, and mechanical stresses associated with freezing.

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Comparative Evaluation of S–γ Model and AMUSIG Model in Predicting Droplet Size Distributions in Narrow-Gap Homogenizers

Investigators: Chun Yuan Kung (Purdue PMP student), Thomas Eppinger (Siemens), Petr Kazarin (Purdue Post Doc, now at IMA Life)

In the dynamic working field of emulsion processing, the accurate prediction of droplet size distribution is an important factor in enhancing and improving efficiency and product quality in various industries. This project resulted in a comparative analysis of the performance of two models, the S-γ model and the Adaptive Multiple Size Group (AMUSIG) model under various conditions by using STAR- CCM+ simulation software, allowing the provided analysis to methodically verify hypotheses, designs, and models in a controlled environment.

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