Abstract
Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.