Crommelin Daan J A, Volkin David B, Hoogendoorn Karin H, Lubiniecki Anthony S, Jiskoot Wim
Department of Pharmaceutics, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
J Pharm Sci. 2021 Feb;110(2):627-634. doi: 10.1016/j.xphs.2020.11.015. Epub 2020 Nov 23.
Once Covid-19 vaccines become available, 5-10 billion vaccine doses should be globally distributed, stored and administered. In this commentary, we discuss how this enormous challenge could be addressed for viral vector-based Covid-19 vaccines by learning from the wealth of formulation development experience gained over the years on stability issues related to live attenuated virus vaccines and viral vector vaccines for other diseases. This experience has led -over time- to major improvements on storage temperature, shelf-life and in-use stability requirements. First, we will cover work on 'classical' live attenuated virus vaccines as well as replication competent viral vector vaccines. Subsequently, we address replication deficient viral vector vaccines. Freeze drying and storage at 2-8 °C with a shelf life of years has become the norm. In the case of pandemics with incredibly high and urgent product demands, however, the desire for rapid and convenient distribution chains combined with short end-user storage times require that liquid formulations with shelf lives of months stored at 2-8 °C be considered. In confronting this "perfect storm" of Covid-19 vaccine stability challenges, understanding the many lessons learned from decades of development and manufacturing of live virus-based vaccines is the shortest path for finding promising and rapid solutions.
一旦有了新冠病毒疫苗，全球应分发、储存和接种50亿至100亿剂疫苗。在这篇评论文章中，我们将探讨如何通过借鉴多年来在减毒活病毒疫苗和用于其他疾病的病毒载体疫苗稳定性问题方面积累的丰富配方开发经验，来应对基于病毒载体的新冠病毒疫苗这一巨大挑战。随着时间的推移，这一经验已带来了储存温度、保质期和使用稳定性要求方面的重大改进。首先，我们将介绍“经典”减毒活病毒疫苗以及具有复制能力的病毒载体疫苗的相关工作。随后，我们将探讨复制缺陷型病毒载体疫苗。冻干并在2至8摄氏度下储存数年已成为常态。然而，在产品需求极高且紧急的大流行情况下，由于需要快速便捷的分销链以及终端用户的短时间储存，因此需要考虑在2至8摄氏度下保质期为数月的液体制剂。在应对新冠病毒疫苗稳定性挑战这一“完美风暴”时，了解从数十年基于活病毒疫苗的开发和生产中学到的诸多经验教训，是找到有前景且快速解决方案的最短路径。
