Particulate contamination in parenteral fluid from glass ampoules: compliance assessment and comparative analysis of needle types and ampoule-breaking strategies

Roland B van den Berg; Elizabeth Serbée-Wijker; Elsbeth M Westerman; Jörn O Streefkerk; Erik B Wilms; Mirjam Crul; Eleonora L Swart

doi:10.1016/j.ejps.2025.107184

Particulate contamination in parenteral fluid from glass ampoules: compliance assessment and comparative analysis of needle types and ampoule-breaking strategies

Eur J Pharm Sci. 2025 Jun 25:212:107184. doi: 10.1016/j.ejps.2025.107184. Online ahead of print.

Authors

Roland B van den Berg¹, Elizabeth Serbée-Wijker², Elsbeth M Westerman³, Jörn O Streefkerk⁴, Erik B Wilms⁵, Mirjam Crul², Eleonora L Swart²

Affiliations

¹ Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands; Department of Hospital Pharmacy, Haaglanden Medisch Centrum, The Hague, the Netherlands. Electronic address: r.vandenberg2@amsterdamumc.nl.
² Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, location Vrije Universiteit, Amsterdam, the Netherlands.
³ Department of Hospital Pharmacy, Haaglanden Medisch Centrum, The Hague, the Netherlands.
⁴ Department of Intensive Care Medicine, Haaglanden Medisch Centrum, Den Haag, the Netherlands.
⁵ Department of Hospital Pharmacy, Haga Teaching Hospital, The Hague, the Netherlands; Apotheek Haagse Ziekenhuizen, The Hague, the Netherlands.

PMID: 40578456
DOI: 10.1016/j.ejps.2025.107184

Abstract

Particulate contamination in parenteral fluid poses potential risks when administered. Guidelines recommend using filter needles during fluid withdrawal from glass ampoules. However, studies supporting these guidelines exhibit certain limitations, preventing definitive conclusions regarding the superiority of filter needles over conventional needles. Additionally, no assessment of compliance with the European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) standards on particulate contamination has been conducted for either needle type. The aim of this study was to determine if both needle types, combined with either a manual breaking technique or an ampoule-breaking device, met these standards. Ten drugs were selected to assess particulate contamination in parenteral fluid after fluid withdrawal from glass ampoules using a filter or conventional needle, combined with either a manual breaking technique or an ampoule-breaking device. Each drug included 10 samples, totaling 100 samples per method and 400 samples overall. Samples underwent visual inspection and sub-visible particle analysis using the light obscuration (LO) particle count test. Results were compared to Ph. Eur. and USP standards and the Friedman test was used to assess differences in sub-visible particles between the four methods. Both needle types, in combination with either the manual breaking technique or the ampoule-breaking device, complied with Ph. Eur. and USP standards. Furthermore, no statistically significant differences were observed between the four methods regarding particles ≥10 µm (p = 0.227) and ≥25 µm (p = 0.237). Both needle types and breaking techniques are suitable for use during the aseptic drug reconstitution of glass ampoules. However, based on these results, the use of filter needles for fluid withdrawal from glass ampoules did not demonstrate additional benefit. Omitting them could potentially save time and reduce unnecessary waste.

Keywords: Compliance testing; Drug reconstitution; Parenteral solution; Particulate contamination; Sub-visible particles.