Affiliation:
1. WuXi Biologics (Shanghai) Co., Ltd Drug Product Development, , 190 Hedan Road, Waigaoqiao Free Trade Zone, Shanghai, 200131, China
Abstract
Abstract
Background
Lyophilized drug products with high protein concentration often perform long reconstitution time, which is inconvenient for clinical use. The objective of this work is to achieve short reconstitution time with multiple and combined strategies.
Methods
Here, we describe the following approaches that lead to reduction of reconstitution time, including adding annealing step, decreasing headspace pressure, decreasing protein concentration with reducing diluent volume, increasing high surface-area-to-height ratio of the cakes, increasing frequency of swirling and diluent temperature.
Results
Among these strategies, reducing diluent volume to achieve high protein concentration and reducing headspace pressure show markedly reduction of reconstitution time. Moreover, we propose combined strategies to mitigate the reconstitution time, at the same time, to achieve same target dose in clinics.
Conclusions
Therefore, this paper provides insights on the application of multiple strategies to accelerate the reconstitution of lyophilized drug products with high concentration, and facilitates their widespread clinical application.
Funder
Drug Product Development, Shang Hai WuXi Biologics Inc
Publisher
Oxford University Press (OUP)
Subject
Immunology,Immunology and Allergy
Reference22 articles.
1. Subcutaneous delivery of high-dose/volume biologics: current status and prospect for future advancements;Badkar;Drug Des Devel Ther,2021
2. Lyophilization strategies for development of a high-concentration monoclonal antibody formulation: benefits and pitfalls;Bhambhani;Am Pharm Rev,2010
3. US FDA-approved therapeutic antibodies with high-concentration formulation: summaries and perspectives;Wang;Antib Ther,2021
4. Challenges in the development of high protein concentration formulations;Shire;J Pharm Sci,2004
5. Rational design of lyophilized high concentration protein formulations-mitigating the challenge of slow reconstitution with multidisciplinary strategies;Cao;Eur J Pharm Biopharm,2013