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. 2024 Jun 21;31(4):358-362.
doi: 10.1136/ejhpharm-2022-003604.

Container closure integrity testing and process validation of closed system transfer devices for aseptic reconstitution of drug vials connected to fluid bags

Roland B van den Berg  1 , Kübra Akgöl  2 , Eleonora L Swart  3 , Bastiaan Nuijen  2 , Mirjam Crul  3
Affiliations

Container closure integrity testing and process validation of closed system transfer devices for aseptic reconstitution of drug vials connected to fluid bags

Roland B van den Berg et al. Eur J Hosp Pharm. .

Abstract

Objectives: The closure integrity and process validation of closed system transfer devices (CSTDs) should be confirmed before implementation in clinical settings. We aimed to investigate the closure integrity and validate the aseptic procedure of two types of CSTDs by using a combination of the dye ingress test and a media fill test.

Methods: The dye ingress test with methylene blue was used for both CSTDs with 10 samples of drug vials of three brands. A media fill test was performed with both CSTDs (300 samples per CSTD, 150 carried out in a safety cabinet and 150 under non-classified environmental conditions).

Results: In all samples of both CSTDs, methylene blue was absent after visual inspection and spectrophotometric analysis. The nutrient media of one sample with CSTD A and none of the CSTD B samples were contaminated when reconstituted in a GMP grade A environment. Under non-classified environmental conditions, one sample of CSTD A and two samples of CSTD B were contaminated.

Conclusions: Both CSTDs connected to the drug vials met the terms of closure integrity by using the dye ingress test. The aseptic procedure of CSTD B was validated with the media fill test when reconstituted in a GMP grade A environment, but failed for CSTD A. Both CSTDs failed the media fill test when reconstituted under non-classified environmental conditions.

Keywords: chemical safety; drug incompatibility; pharmaceutical preparations; pharmacopoeia; safety.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Connected closed system transfer device (CSTD) A (left) and CSTD B (right).
See this image and copyright information in PMC

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