Frequency and component analysis of contaminants generated in preparation of anticancer agents using closed system drug transfer devices (CSTDs)

Abstract

Occupational exposure of anticancer agents during their preparation has been recognized as a serious hazard. Closed system drug transfer devices (CSTDs) enable “safe” preparation of agents for medical personnel and ensure a safe hospital environment. However, artificial particles of infusion materials have been reported during CSTD use. Here, the incidence of insoluble fine particles during preparation of anticancer agents using CSTDs was examined. Visible insoluble fine particles were found in 465 (9.4%) of 4948 treatment cases at Ehime University Hospital with CSTD use. Contaminants occurred more frequently during preparation of monoclonal antibodies than cytotoxic anticancer agents (19.4% vs. 4.1%, respectively, P < 0.01). A similar survey was conducted at nine hospitals to investigate the incidence of insoluble fine particles with or without CSTDs. Insoluble fine particles were detected in 113 (15.4%) of 732 treatment cases during preparation of monoclonal antibodies with CSTD use. In contrast, the occurrence of insoluble fine particles without CSTDs was found in only 3 (0.073%) of 4113 treatment cases. Contamination with CSTDs might cause harmful effects on patients during cancer therapy. We strongly recommend the use of in-line filters combined with infusion routes after CSTD use to avoid contamination-associated adverse events.

Clinical Oncology Society of Australia Position Statement: 2022 update to the safe handling of monoclonal antibodies in healthcare settings

“…However, since the first COSA Position Statement, several consensus guidelines and position statements for the safe handling of mABs have been published, 3,6–8 as well as review papers 9,10,12 and commentary 11 on the occupational exposure risks. Among the relevant literature published since the 2013 Position Statement, literature relating specifically to pertuzumab, 13,14 closed system transfers devices (CSTDs) used with mABs, 3,18–22 a case report relating to staff sensitization to a mAB 5 , and the nomenclature change to mABs, 17 was identified.…”

“…In the last few years, there have been several papers published relating to the use of CSTDs in the preparation and administration of mABs 18–22 . While CSTDs provide enhanced protection against potentially hazardous exposures to healthcare workers, 3,13 performance standards for evaluation of CSTD containment are not yet available 23 .…”

“…Insoluble fine particles in the final product were detected when CSTDs were used in the preparation of mABs, but the clinical significance of this finding is uncertain 20,21 . Institutions should consider these potential issues when selecting CSTDs.…”

Safe handling of cytostatic drugs: recommendations from independent science

“…The CM-directive (Directive 2004/37/EC of the European Parliament and of the Council on the Protection of Workers from the Risks Related to Exposure to Carcinogens or Mutagens at Work) is up for revision in 2023 or 2024. In the run-up to that process, the producers of CSTDs are lobbying strongly to get their devices included in the guidelines,29 despite the lack of independent scientific evidence to support their added value compared with the method of using spikes,30 the higher costs for healthcare systems when implementing CSTDs,31 and the emerging evidence that, in some cases, CSTDs can compromise the quality of drug products through particle formation 32 33. Following persistent pressure from professional associations such as the European Oncology Nursing Society (EONS), European Cancer Organisation (ECO) and ESOP, the Directorate-General of Employment, Social Affairs and Inclusion of the EU launched an investigation to study the current situation in its member states.…”

Developing a flowchart to evaluate the use of Closed System Drug-Transfer Devices with monoclonal antibodies: Focus on the clinical trial setting

“…This issue has grown in importance in light of recent published articles imposing the challenges associated with the use of CSTDs in preparations with biologics. [30][31][32][33][34][35][36][37][38][39][40] All of this makes the debate on whether or not to use CSTD a hot topic in daily pharmacy practice, especially in a clinical trial setting where safety data of investigational medicinal products (IMP) are frequently not available and the compatibility of CSTD devices and IMP is often unknown.…”