Department of Pharmacy, Grenoble Alpes University Hospital, Grenoble, France; INSERM U1055, Laboratory of Fundamental and Applied Bioenergetics, University Grenoble Alpes, Grenoble, France.
Department of Pharmacy, Grenoble Alpes University Hospital, Grenoble, France.
Eur J Pharm Sci. 2022 Dec 1;179:106275. doi: 10.1016/j.ejps.2022.106275. Epub 2022 Aug 17.
Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process.
自动化复合设备（ACD）越来越多地用于肠外营养（PN）袋的生产，其采购必须经过充分的考虑。法律要求这些 ACD 具备资质，但没有具体规定要进行哪些测试。基于质量设计（QbD）的风险方法允许定义质量目标产品概况，以便为每个单位获得最佳的 ACD，并通过风险分析来定义关键质量属性（CQA）。这些 CQA 将允许定义在资格认证期间执行的测试。经过资格认证的 ACD 是一个 12 泵体积系统。PN 袋的 CQA 包括无菌、精确和准确的生产，并具有足够的稳定性。在运行资格认证期间，进行了体积精度测试，在性能资格认证期间，进行了冲洗体积、介质填充、环境微生物完整性、控制袋的无菌性和生产测试。最后，所有测试的结果都是确定的（除了一些主要由于分析偏差导致的结果），该 ACD 被认为可以在控制环境中生产无菌袋，精确（相对标准偏差<4%）和准确（重量的平均偏差<1%，其他控制<7%），具有足够的稳定性。基于质量设计的风险方法允许我们根据需要获得最佳的 ACD，并对生产过程的相关要素进行资格认证。
