稀释还是不稀释:基因药物的名义滴度剂量。

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pharmaceutical Statistics Pub Date : 2024-06-25 DOI:10.1002/pst.2406
Paul Faya, Tianhui Zhang
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引用次数: 0

摘要

重组腺相关病毒(AAV)已成为许多基因治疗应用的流行平台。基于 AAV 的产品的强度是影响药物疗效的关键质量属性,以载体基因组的浓度或物理滴度来衡量。由于患者的用药剂量是根据滴度测量得出的,因此生产商必须确保药物产品的测量滴度接近批次的实际浓度。一直以来,剂量计算都是使用药物产品标签上报告的测定滴度。然而,根据最近的监管指南,申办者现在应该在药品标签上标注名义滴度或 "目标 "滴度。对基因治疗产品的这一新要求可能会给工艺和分析变异性带来挑战。特别是,制造商必须决定是否需要在药物产品阶段对药物物质进行稀释,以使其强度符合标称值。在本文中,我们提出了两种简单明了的统计方法来帮助制造商做出稀释决定。这些方法利用对工艺和分析变异性的理解来计算达到所需药物产品滴度的概率。我们还提供了一种方法,用于确定最佳的化验复制策略,以达到满足药物产品释放规格的预期概率。
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To Dilute or Not to Dilute: Nominal Titer Dosing for Genetic Medicines.

Recombinant adeno-associated virus (AAV) has become a popular platform for many gene therapy applications. The strength of AAV-based products is a critical quality attribute that affects the efficacy of the drug and is measured as the concentration of vector genomes, or physical titer. Because the dosing of patients is based on the titer measurement, it is critical for manufacturers to ensure that the measured titer of the drug product is close to the actual concentration of the batch. Historically, dosing calculations have been performed using the measured titer, which is reported on the drug product label. However, due to recent regulatory guidance, sponsors are now expected to label the drug product with nominal or "target" titer. This new expectation for gene therapy products can pose a challenge in the presence of process and analytical variability. In particular, the manufacturer must decide if a dilution of the drug substance is warranted at the drug product stage to bring the strength in line with the nominal value. In this paper, we present two straightforward statistical methods to aid the manufacturer in the dilution decision. These approaches use the understanding of process and analytical variability to compute probabilities of achieving the desired drug product titer. We also provide an approach for determining an optimal assay replication strategy for achieving the desired probability of meeting drug product release specifications.

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来源期刊
Pharmaceutical Statistics
Pharmaceutical Statistics 医学-统计学与概率论
CiteScore
2.70
自引率
6.70%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Pharmaceutical Statistics is an industry-led initiative, tackling real problems in statistical applications. The Journal publishes papers that share experiences in the practical application of statistics within the pharmaceutical industry. It covers all aspects of pharmaceutical statistical applications from discovery, through pre-clinical development, clinical development, post-marketing surveillance, consumer health, production, epidemiology, and health economics. The Journal is both international and multidisciplinary. It includes high quality practical papers, case studies and review papers.
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