Leveraging Lyophilization Modeling for Reliable Development, Scale-up and Technology Transfer

• Published in: AAPS PharmSciTech 2019-07, Vol.20 (7), p.263
• Main Authors: Zhou, Deliang, Shang, Sherwin, Tharp, Ted, Jameel, Feroz, Sinha, Kushal, Nere, Nandkishor K.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Research Article
• ISSN: 1530-9932
• DOI: 10.1208/s12249-019-1478-9

Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient, K v , and the cake resistance, R p . The classical gravimetric method used to measure K v is tedious, time- and resource-consuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both K v and R p directly from an experimental run ( e.g. , temperature and Pirani profiles). The new methodology is demonstrated using 5% w / v mannitol model system. The values of K v obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing.