Lambert Peter, McIntosh Michelle P, Widmer Mariana, Evans Lawrence, Rauscher Megan, Kuwana Rutendo, Theunissen Fiona, Yeager Beth, Petach Helen
1Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.
2Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
J Pharm Policy Pract. 2020 May 15;13:14. doi: 10.1186/s40545-020-00205-7. eCollection 2020.
The use of quality injectable oxytocin effectively prevents and treats postpartum hemorrhage, the leading cause of maternal death worldwide. In low- and middle-income countries (LMICs), characteristics of oxytocin-specifically its heat sensitivity-challenge efforts to ensure its quality throughout the health supply chain. In 2019, WHO, UNFPA and UNICEF released a joint-statement to clarify and recommend that oxytocin should be kept in the cold chain (between 2 and 8 °C) during transportation and storage; however, confusion among stakeholders in LMICs persists.
To further support recommendations in the WHO/UNFPA/UNICEF joint-statement, this paper reviews results of oxytocin quality testing in LMICs, evaluates product stability considerations for its management and considers quality risks for oxytocin injection throughout the health supply chain. This paper concludes with a set of recommended actions to address the challenges in maintaining quality for a heat sensitive pharmaceutical product.
Due to the heat sensitivity of oxytocin, its quality may be degraded at numerous points along the health supply chain including: At the point of manufacture, due to poor quality active pharmaceutical ingredients; lack of sterile manufacturing environments; or low-quality manufacturing processesDuring storage and distribution, due to lack of temperature control in the supply chain, including cold chain at the end user health facilitySafeguarding the quality of oxytocin falls under the purview of national medicines regulatory authorities; however, regulators in LMICs may not adhere to good regulatory practices.
Storing oxytocin from 2 to 8 °C throughout the supply chain is important for maintaining its quality. While short temperature excursions may not harm product quality, the cumulative heat exposure is generally not tracked and leads to degradation. National and sub-national policies must prioritize procurement of quality oxytocin and require its appropriate storage and management.
使用优质注射用缩宫素可有效预防和治疗产后出血，而产后出血是全球孕产妇死亡的主要原因。在低收入和中等收入国家（LMICs），缩宫素的特性——尤其是其热敏感性——给确保其在整个卫生供应链中的质量带来了挑战。2019年，世界卫生组织、联合国人口基金和联合国儿童基金会发布了一份联合声明，以澄清并建议缩宫素在运输和储存过程中应保存在冷链（2至8摄氏度）中；然而，低收入和中等收入国家的利益相关者之间仍然存在困惑。
为进一步支持世界卫生组织/联合国人口基金/联合国儿童基金会联合声明中的建议，本文回顾了低收入和中等收入国家缩宫素质量检测的结果，评估了其管理中的产品稳定性考量，并考虑了缩宫素注射液在整个卫生供应链中的质量风险。本文最后提出了一系列建议行动，以应对维持热敏药品质量方面的挑战。
由于缩宫素的热敏感性，其质量可能在卫生供应链的多个环节下降，包括：在生产环节，由于活性药物成分质量差、缺乏无菌生产环境或低质量的生产工艺；在储存和分销环节，由于供应链中缺乏温度控制，包括终端用户医疗机构的冷链。保障缩宫素的质量属于国家药品监管当局的职责范围；然而，低收入和中等收入国家的监管机构可能不遵守良好的监管规范。
在整个供应链中将缩宫素储存在2至8摄氏度对于维持其质量很重要。虽然短时间的温度偏差可能不会损害产品质量，但累积的热暴露通常没有得到跟踪，会导致产品降解。国家和次国家政策必须优先采购优质缩宫素，并要求对其进行适当的储存和管理。
