Pharmaceutical Institute, Eberhard Karls University Tübingen, Tübingen, Germany.
Institute for Clinical Epidemiology and Applied Biometry, Eberhard Karls University Tübingen, Tübingen, Germany.
PLoS One. 2020 Dec 3;15(12):e0243428. doi: 10.1371/journal.pone.0243428. eCollection 2020.
Quality-assured medicines are a principal means of achieving health-related Sustainable Development Goals. An example of quality assurance/quality control (QA/QC) procedures in drug procurement is provided by the operation of the Global Drug Facility (GDF) of the Stop TB Partnership, the largest provider of tuberculosis (TB) medicines to the public sector worldwide.
Procedures and results of GDF's quality assurance/quality control (QA/QC) over the five-year period 2013-2017 were analysed retrospectively. 13,999 batches of 51 different medicines had been procured and reviewed within this period. 1,388 of these batches had been analysed in the laboratories of GDF's external quality control agent (QCA). Assay and dissolution results determined by the manufacturers and by the external QCA were compared using Bland-Altman analysis.
All investigated batches of medicines were in specifications at the time of shipment. The costs for QA/QC were 0.8% of purchase costs. The median time required for chemical analysis was 10 working days. Comparison of the medicine quality analysis results showed for the poorly water-soluble compound rifampicin a bias of 4.4%, with the manufacturers reporting higher values than the external QCA, most likely due to different methods employed for the analysis. Overall 95% limits of agreement (LOAs) were -6.7 to +8.0% for assay, and -10.1 to +11.8% for dissolution. In case of kanamycin injections, 95% LOAs for assay reached -14.5 to +13.2%, largely attributable to samples from one manufacturer who had used a microbiological assay while the external QCA had used an HPLC assay.
GDF's procedures represent a useful benchmark when evaluating QA/QC procedures of other medicine procurement operations. Inter-laboratory comparison using Bland-Altman plots allows to investigate bias and variability in medicine quality control and should be considered as a routine procedure by drug procurement agencies, to identify priorities for further improvements.
有质量保证的药品是实现与健康相关的可持续发展目标的主要手段。全球药品基金（GDF）作为全球最大的公共部门结核病药物供应商，在药品采购中实施质量保证/质量控制（QA/QC）程序就是一个范例。
本研究回顾性分析了 GDF 在 2013-2017 年五年期间的 QA/QC 程序和结果。在此期间，共采购和审查了 13999 批 51 种不同的药品。其中 1388 批在 GDF 外部质量控制代理（QCA）的实验室进行了分析。制造商和外部 QCA 确定的含量和溶出度结果使用 Bland-Altman 分析进行比较。
所有调查批次的药品在发货时均符合规格。QA/QC 成本占采购成本的 0.8%。化学分析的中位时间为 10 个工作日。药物质量分析结果的比较显示，对于水溶性差的化合物利福平，存在 4.4%的偏差，制造商报告的值高于外部 QCA，这很可能是由于分析采用了不同的方法。总体而言，对于含量测定，95%的一致性限（LOA）为-6.7%至+8.0%，对于溶出度，95%的 LOA 为-10.1%至+11.8%。对于卡那霉素注射液，含量测定的 95%LOA 达到-14.5%至+13.2%，这主要归因于一家制造商的样品，该制造商使用微生物测定法，而外部 QCA 使用 HPLC 测定法。
GDF 的程序为评估其他药品采购业务的 QA/QC 程序提供了一个有用的基准。使用 Bland-Altman 图进行实验室间比较可以研究药品质量控制中的偏差和变异性，并且应该作为药物采购机构的常规程序，以确定进一步改进的优先事项。
