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Container closure integrity testing and process validation of closed system transfer devices for aseptic reconstitution of drug vials connected to fluid bags
  1. Roland B van den Berg1,
  2. Kübra Akgöl2,
  3. Eleonora L Swart1,
  4. Bastiaan Nuijen2,
  5. Mirjam Crul1
  1. 1 Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  2. 2 Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands
  1. Correspondence to Roland B van den Berg, Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; r.vandenberg2{at}amsterdamumc.nl

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.

  • drug incompatibility
  • chemical safety
  • pharmacopoeia
  • pharmaceutical preparations
  • safety

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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