Accurate prediction of vaccine stability under real storage conditions and during temperature excursions
Accurate prediction of vaccine stability under real storage conditions and during temperature excursions
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DOI：
10.1016/j.ejpb.2018.01.005
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发表时间：
2018-04-01
影响因子：
4.9
通讯作者：
Clenet, Didier
中科院分区：
文献类型：
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作者：
Clenet, Didier
由于其热敏感性，大多数疫苗从生产到使用都必须冷藏。要成功开展全球免疫计划，确保疫苗的稳定性至关重要。在这种情况下，有两个重要问题至关重要，即：(i) 预测疫苗稳定性；(ii) 防止由于温度超出推荐储存条件（冷链断裂）而导致产品损坏。我们对疫苗强制降解数据应用了先进的动力学和统计分析相结合，以准确描述包含三种变体的多价冻干灭活病毒疫苗的抗原性丧失。大量动力学模型的筛选与统计模型选择方法相结合导致了两步动力学模型的识别。基于动力学分析和实验稳定性数据的预测是一致的，长期稳定性储存条件、温度偏移后和冻干产品实验运输期间的实际值与实际值相差约五个百分点。结果表明，对几个月的强制降解进行建模可用于预测疫苗所承受的各种时间和温度曲线，即长期稳定性、超出标签储存条件的短时间偏移或在环境温度下的运输，且具有高精度。讨论了所提出的基于动力学的方法的制药应用。
Due to their thermosensitivity, most vaccines must be kept refrigerated from production to use. To successfully carry out global immunization programs, ensuring the stability of vaccines is crucial. In this context, two important issues are critical, namely: (i) predicting vaccine stability and (ii) preventing product damage due to excessive temperature excursions outside of the recommended storage conditions (cold chain break). We applied a combination of advanced kinetics and statistical analyses on vaccine forced degradation data to accurately describe the loss of antigenicity for a multivalent freeze-dried inactivated virus vaccine containing three variants. The screening of large amounts of kinetic models combined with a statistical model selection approach resulted in the identification of two-step kinetic models. Predictions based on kinetic analysis and experimental stability data were in agreement, with approximately five percentage points difference from real values for long-term stability storage conditions, after excursions of temperature and during experimental shipments of freeze-dried products. Results showed that modeling a few months of forced degradation can be used to predict various time and temperature profiles endured by vaccines, i.e. long-term stability, short time excursions outside the labeled storage conditions or shipments at ambient temperature, with high accuracy. Pharmaceutical applications of the presented kinetics-based approach are discussed.