Jenke Dennis
Triad Scientific Solutions, LLC, Hawthorn Woods, IL
PDA J Pharm Sci Technol. 2019 Mar-Apr;73(2):135-169. doi: 10.5731/pdajpst.2018.009050. Epub 2018 Oct 25.
Pharmaceutical drug products are packaged in containers so that they can be manufactured, distributed, and stored. During these events in a drug product's life cycle, the drug product and its packaging could interact, resulting in substances leaching from the plastic and accumulating in the drug product. As the leached substances could adversely impact a key quality attribute of the drug product, drug products must be tested to establish which leachables are present and in what quantities.Because a drug product's lifetime can be long, it is common practice to accelerate leaching by using temperatures higher than clinical use conditions. While use of accelerated conditions is a well-accepted practice, there are questions with respect to the means by which the degree of acceleration can be calculated and justified. In this manuscript, experimental data from 10 case studies are used to evaluate commonly utilized, Arrhenius-based approaches to acceleration, and recommendations are made in terms of the proper approaches to be used for concentration and duration extrapolations. Specifically, when accumulation levels are projected from a clinical to an elevated temperature, the Arrhenius model formulated by ASTM for the accelerated aging of medical devices using a Q10 value of 1.5 most frequently provides the best fit to experimental leaching data. Alternatively, when contact durations are projected from a clinical to an elevated temperature, the Arrhenius model reflected in the empirically derived "factor 10 rule," developed for and applied to food contact packaging, most frequently provides the best fit to experimental leaching data. Pharmaceutical drug products are packaged in containers so that they can be manufactured, distributed, and stored. During these events in a drug product's life cycle, the drug product and the plastic systems may interact, resulting in substances leaching from the plastic and accumulating in the drug product. As the leached substances could adversely impact a key quality attribute of the drug product, drug products must be tested to establish what leachables are present and in what quantities.Because a drug product's lifetime can be long, it is common practice to accelerate leaching by using temperatures higher than clinical use conditions. While use of accelerated conditions is a well-accepted practice, there are questions with respect to the means by which the degree of acceleration can be calculated and justified. In this manuscript, experimental data from 10 case studies are used to evaluate commonly utilized approaches to acceleration, and recommendations are made in terms of the proper approaches to be used for concentration and duration extrapolations.
药品被包装在容器中，以便于生产、分销和储存。在药品生命周期的这些过程中，药品及其包装可能会相互作用，导致物质从塑料中浸出并在药品中积累。由于浸出的物质可能会对药品的关键质量属性产生不利影响，因此必须对药品进行测试，以确定存在哪些可浸出物以及其含量。由于药品的保质期可能很长，通常的做法是通过使用高于临床使用条件的温度来加速浸出。虽然使用加速条件是一种被广泛接受的做法，但关于如何计算和证明加速程度的方法仍存在问题。在本手稿中，使用来自10个案例研究的实验数据来评估常用的基于阿伦尼乌斯的加速方法，并就用于浓度和时间外推的适当方法提出建议。具体而言，当从临床温度推算到升高温度下的积累水平时，美国材料与试验协会（ASTM）制定的使用1.5的Q10值进行医疗器械加速老化的阿伦尼乌斯模型最常能与实验浸出数据最佳拟合。或者，当从临床温度推算到升高温度下的接触时间时，为食品接触包装开发并应用的经验推导的“10倍规则”中反映的阿伦尼乌斯模型最常能与实验浸出数据最佳拟合。药品被包装在容器中，以便于生产、分销和储存。在药品生命周期的这些过程中，药品和塑料系统可能会相互作用，导致物质从塑料中浸出并在药品中积累。由于浸出的物质可能会对药品的关键质量属性产生不利影响，因此必须对药品进行测试，以确定存在哪些可浸出物以及其含量。由于药品的保质期可能很长，通常的做法是通过使用高于临床使用条件的温度来加速浸出。虽然使用加速条件是一种被广泛接受的做法，但关于如何计算和证明加速程度的方法仍存在问题。在本手稿中，使用来自10个案例研究的实验数据来评估常用的加速方法，并就用于浓度和时间外推的适当方法提出建议。
