(368av) Mechanistic Modeling of Continuous Lyophilization Via Suspended Vials

Lyophilization (aka freeze drying) is a process used to increase the stability of various therapeutics in biopharmaceutical manufacturing. Recently, freeze drying has been shown to provide long-term stability for mRNA vaccines, e.g. COVID-19 vaccines, which enables these vaccines to be delivered in countries that lack a cold supply chain [1]. This potential could help improve society’s ability to respond to future pandemics. Three stages of lyophilization comprise (1) freezing, (2) primary drying, and (3) secondary drying. In conventional lyophilization, the product contained in a glass vial is cooled or heated in a chamber, which is performed as a batch process.

Continuous lyophilization is considered an emerging technology that has been of interest during recent years as the pharmaceutical industry has been moving toward continuous manufacturing [2]. The benefits of continuous lyophilization have been discussed and demonstrated, including improved quality control, greater flexibility, drying time reduction, better heat transfer uniformity, and smaller equipment size. To achieve continuous lyophilization, various concepts have been proposed, e.g., spin lyophilization [1] and suspended vials [3].

Mechanistic modeling has been extensively used to guide the design, optimization, monitoring, and control of lyophilization, with a large number of models established for a conventional lyophilization process. However, its applications to continuous lyophilization are currently very limited. This work discusses mechanistic modeling strategies and applications for continuous lyophilization. Several mechanistic models for conventional lyophilization are first discussed. Subsequently, state-of-the-arts models for continuous lyophilization are developed. Finally, applications of the resulting models are demonstrated.

Acknowledgement: This research was supported by the U.S. Food and Drug Administration under the FDA BAA-22-00123 program, Award Number 75F40122C00200.

References

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[2] Pisano, R., Arsiccio, A., Capozzi, L.C., Trout, B.L., 2019. Achieving continuous manufacturing in lyophilization: Technologies and approaches. Eur. J. Pharm. Biopharm. 142, 265–279.

[3] Capozzi, L.C., Trout, B.L., Pisano, R., 2019. From batch to continuous: Freeze-drying of suspended vials for pharmaceuticals in unit-doses. Industrial & Engineering Chemistry Research 58, 1635–1649.

[4] Fissore, D., Pisano, R., Barresi, A.A., 2015. Using mathematical modeling and prior knowledge for QbD in freeze-drying processes, in: Jameel, F., Hershenson, S., Khan, M.A., Martin-Moe, S. (Eds.), Quality by Design for Biopharmaceutical Drug Product Development. Springer, New York, pp. 565–593