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3PC-006 Container closure integrity testing and process validation of closed system transfer devices for aseptic reconstitution of drug vials connected to fluid bags
  1. R Van Den Berg1,
  2. K Akgöl2,
  3. E Swart1,
  4. B Nuijen2,
  5. M Crul1
  1. 1Amsterdam Umc – Vrije Universiteit Amsterdam, Department of Pharmacy and Clinical Pharmacology, Amsterdam, The Netherlands
  2. 2Netherlands Cancer Institute – Antoni Van Leeuwenhoek, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands


Background and Importance The closure integrity and process validation of closed system transfer devices (CSTD) should be assured before implementation in clinical settings. However, there are no gold standard methods for Container Closure Integrity Testing (CCIT) of CSTDs.

Aim and Objectives We aimed to investigate the closure integrity and validate the aseptic procedure of two types of CSTDs (Vial-Mate from Baxter, hereafter called CSTD A and Ecoflac Connect from B. Braun, hereafter called CSTD B) by using a combination of the dye ingress test and a media fill test.

Material and Methods The dye ingress test with methylene blue was used as CCIT for both CSTDs with ten samples of meropenem drug vials of three brands (n = 60). A media fill test was performed with both CSTDs (n = 300 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, reconstituted in a safety cabinet, was contaminated whereas none of the CSTD B samples with reconstitution in a GMP grade A environment were contaminated. Under non-classified environmental conditions, one sample of CSTD A and two samples of CSTD B were contaminated.

Conclusion and Relevance In conclusion, both CSTDs connected to meropenem vials of three brands are in compliance with the closure integrity by using the dye ingress. The aseptic procedure of CSTB B was validated with the media fill test when reconstituted in a GMP grade A environment, but failed for CSTD A. The added value of CSTDs in a hospital (pharmacy) remains debatable without a clearly demonstrated closure integrity when bedside reconstitution is done. Hospital pharmacists are strongly advised to perform sufficient and adequate closure integrity tests with CSTDs before implementing them in clinical use.

Conflict of Interest No conflict of interest

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