SBIR Phase II: Development of Polymer Gel-Based Indicators to Monitor the Exposure of Shipments of Pharmaceuticals to Harmful Temperatures

这个小型企业创新研究阶段（SBIR）II项目的更广泛的影响/商业潜力是帮助检测即将给予患者的药物是否在运输或储存过程中因暴露于接近或低于水的冻结温度的极冷温度而受损。许多药物，特别是疫苗，如果暴露在接近冷冻的条件下，就会失去效力。鉴于对药物温控储存和分销的监管日益严格，分销模式不断变化（直接向患者发货的增加），迫切需要以更高的可靠性和成本效益证明药物是否会因暴露于有害温度而失去效力。SBIR II项目的结果将成为一个指标，为药品供应链沿着的工人提供有关药品是否遇到有害温度以及这种情况持续时间的信息。有害温度和暴露时间都是确定药物是否受到损害所需的关键数据。确实存在指示是否暴露于有害温度的技术，然而，暴露时间的指示是混乱的，难以辨别。在第二阶段SBIR计划中拟议的研究如果成功，将为昂贵的电子设备提供可靠的替代方案。该设备的好处包括防止损坏的产品到达患者手中，帮助企业以具有成本效益的方式遵守法规，并减少药品浪费。该小型企业创新研究第二阶段项目旨在开发时间温度指示器（TTI），可靠地指示药品运输暴露于接近水冰点的有害低温。这项技术将是第一项能够显示这种暴露持续时间的化学技术。如果发生有害暴露，托运人可以使用这些指示器提供的时间和温度数据的组合来评估药物是否真正受损。结果，真正受损的药物被丢弃，不给患者服用。该专利指示剂采用了一种特殊配方的聚合物水凝胶，在冷却时，该水凝胶会从膨胀状态转变为塌陷状态。的动力学和温度依赖性的转变是高度可调的。该第二阶段项目的目标包括改进配方和合成方法，以制备具有高度可靠的溶胀-收缩转变的聚合物凝胶。然后将这些凝胶加入到专门设计的外壳中，以获得TTI原型。将设计简单的手动机器来制备TTI原型。将对这些TTI的性能进行确认：公司将证明这些TTI符合最低质量要求。此后，该项目将通过测量加速储存后的性能来测试TTI的稳定性，并对拟议的TTI原型进行标准运输测试。由于这些指标的可靠性是一个关键的产品属性，本项目将确定引入可变性的合成和工艺步骤，并相应地解决这些问题。

The broader impact/commercial potential of this Small Business Innovation Research Phase (SBIR) II project is to help detect whether pharmaceuticals about to be administered to patients have been damaged during shipment or storage by exposure to very cold temperatures close to or below the freezing temperature of water. Many pharmaceuticals, especially vaccines, lose their potency if exposed to near-freezing conditions. In light of tightening regulations with respect to the temperature-controlled storage and distribution of pharmaceuticals and changing distribution models (increase in direct-to-patient shipments), there is a critical need to demonstrate with greater reliability and in a cost-effective manner whether pharmaceuticals lose their potency due to exposure to harmful temperatures. The result of this SBIR II project will be an indicator that will provide workers along the pharmaceutical supply chain information about whether a pharmaceutical encountered harmful temperatures and the duration of such an encounter. Both harmful temperature and duration of exposure are critical pieces of data required to determine whether a pharmaceutical has been compromised. Technologies do exist that indicate whether an exposure to a harmful temperature has occurred, however, the indication of time of exposure is muddled and difficult to discern. The proposed research in this Phase II SBIR program, if successful, will offer a reliable alternative to costly electronic devices. The benefits of this device include preventing damaged product from reaching patients, helping companies remain in compliance with regulations in a cost-effective manner and reducing pharmaceutical waste.This Small Business Innovation Research Phase II project aims to develop Time Temperature Indicators (TTIs) that reliably indicate exposure of pharmaceutical shipments to harmful cold temperatures near the freezing point of water. This technology will be the first chemical-based technology capable of indicating the duration of such exposures. If a harmful exposure occurs, the combination of time and temperature data provided by these indicators can be used by the shipper to evaluate whether a pharmaceutical was truly compromised. As a result, pharmaceuticals that have been truly compromised are discarded and not administered to the patient. The patented indicators utilize a specially formulated polymer hydrogel that undergoes a volume transition from a swollen to a collapsed state upon cooling. The kinetics and the temperature dependence of the transition are highly tunable. The objectives of this Phase II project include refining formulations and synthesis methods to prepare polymer gels with highly reliable swollen-shrunken transitions. These gels will then be incorporated into specially designed housings to obtain TTI prototypes. Simple manual-driven machines will be designed to prepare the TTI prototypes. The performance of these TTIs will be validated: the company will demonstrate that these TTIs meet a minimum quality requirement. Thereafter the project will test the stability of the TTIs by measuring performance after accelerated storage and the proposed TTI prototypes will be subjected to standard transit tests. As the reliability of these indicators is a key product attribute, this project will identify the synthesis and process steps that introduce variability and address them accordingly.