van den Born-Bondt Tessa, Huizinga Harmen P S, Kappert Koen R, Westra Hans H, van Zanten Jacoba, Woerdenbag Herman J, Maurer Jacoba M, Gareb Bahez
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Pharmaceutics. 2025 Jan 7;17(1):74. doi: 10.3390/pharmaceutics17010074.
Parenteral drug products manufactured under GMP conditions should be visually inspected for defects and particulate contamination by trained and qualified personnel. Although personnel qualification is required, no practical protocols or formal guidelines are available for the development of qualification test sets (QTSs) used for qualification procedures. The current practice is to either procure a standardized QTS from a commercial supplier or amass sufficient manufacturing rejects during visual inspection procedures to compile in-house QTSs. However, both strategies inherently possess disadvantages and limitations. The objective of this study was to develop a manufacturing protocol for an optimal and adaptable QTS for training and qualification procedures. We combined the results of a literature search, survey of five Dutch hospital pharmacy compounding facilities, semi-structured personnel interviews, and extensive pre-GMP formulation studies to develop an optimal and adaptable QTS manufacturing protocol. The literature search did not identify a manufacturing protocol for an optimal and adaptable QTS, but did identify specifications and requirements for optimal QTSs. The survey among hospital pharmacy compounding facilities revealed considerable variability in the qualification procedures and used QTSs. Semi-structured personnel interviews and pre-GMP formulation studies demonstrated that defects encountered during routine productions could be realistically simulated with pharmaceutical-grade excipients. As a proof-of-concept, we manufactured two different QTSs under GMP conditions and assessed these for formal GMP training and qualification purposes, which were considered a significant improvement compared to using manufacturing rejects. To the best of our knowledge, this is the first study presenting these data and our adaptable protocol, which is provided in the Supplemental Materials, may aid compounding facilities in the standardization, training, and qualification of personnel involved in visual inspection procedures.
在GMP条件下生产的注射用药品应由经过培训且具备资质的人员进行目视检查，以发现缺陷和微粒污染。尽管需要人员具备资质，但目前尚无用于资质认定程序的资质测试集（QTS）开发的实用方案或正式指南。当前的做法要么是从商业供应商处采购标准化的QTS，要么在目视检查过程中收集足够多的生产不合格品以编制内部QTS。然而，这两种策略都存在固有的缺点和局限性。本研究的目的是制定一种用于培训和资质认定程序的最佳且适用的QTS生产方案。我们综合了文献检索结果、对荷兰五家医院药房配制设施的调查、半结构化人员访谈以及大量GMP前制剂研究结果，以制定最佳且适用的QTS生产方案。文献检索未找到最佳且适用的QTS生产方案，但确定了最佳QTS的规格和要求。医院药房配制设施的调查显示，资质认定程序和所使用的QTS存在很大差异。半结构化人员访谈和GMP前制剂研究表明，使用药用级辅料可以真实模拟常规生产过程中遇到的缺陷。作为概念验证，我们在GMP条件下生产了两种不同的QTS，并对其进行了正式的GMP培训和资质认定评估，与使用生产不合格品相比，这被认为有显著改进。据我们所知，这是第一项展示这些数据的研究，我们在补充材料中提供的适用方案可能有助于配制设施对目视检查程序相关人员进行标准化、培训和资质认定。
