Abstract
The aim of this study was to review the literature regarding the external contamination of commercial vials by antineoplastic drugs. A PubMed and CINAHL searches from 1 January 1990 to 1 May 2018 was performed with the terms: « antineoplastic agents », « environmental monitoring », « drug packaging », « vials » and « contamination ». Articles that presented results on the external contamination of commercial vials were included. Twenty-four articles were identified from 11 countries. A total of 4248 vials were sampled from 28 manufacturers. Traces were found on 56% (2379/4248) of vials. A maximum of 150 000 ng was measured on a glass vial of fluorouracil. This literature review showed that the exterior of the majority of commercial antineoplastic vials was contaminated. Manufacturers should limit this contamination. Centres are also encouraged to clean the vials on receipt. Personal protection equipment should be worn at all steps of the drug-use process.
Keywords: antineoplastic agents, drug packaging, vials, contamination, environmental monitoring
Introduction
Reports have shown that surfaces from healthcare centres are contaminated with antineoplastic drugs. Occupational exposure to these drugs can have adverse health effects on the workers.1 This contamination was observed in Canada, the USA, Europe, Asia and Australia.2–5 Progress was shown over the years which can be attributed to an increase in awareness, implementation of policies and safe handling practices.6 7 Despite these measures, antineoplastic drug traces are measured on surfaces. The source of this contamination cannot be clearly identified. It can come from spills, compounding or administration. The patients themselves are a source of contamination via their excreta but also via their skin.8
In addition, the exterior of commercial vials is often contaminated. The interior of shipping totes has also been shown to be contaminated.9 Receipt is at beginning of the path followed by antineoplastic drugs, thus contamination at this step can impact all of the subsequent handlings.
Our objective was to review the literature about the contamination of the exterior of commercial containers of antineoplastic drugs.
Methods
A literature review was conducted on PubMed and CINAHL: « antineoplastic agents » AND (« environmental monitoring » OR« contamination ») AND (« drug packaging » OR « vials »). Manual search from the reference lists of articles included and Google Scholar was also done. Articles published between 1 January 1990 and 1 May 2018 were searched. Studies were included based on title and abstract. We included experimental studies that presented results about the contamination of the exterior of antineoplastic drug containers. We excluded studies that only presented results about visual contamination of containers or that evaluated cleaning techniques. Articles in English and French were included as the authors were proficient in both languages. Data pertaining to contamination of the exterior of antineoplastic drug containers (before any cleaning) were extracted from full texts. Descriptive statistics were performed.
Results
Twenty-six studies were selected (13 from PubMed and 13 from manual search). Two studies were excluded because they only presented results of the visual contamination of containers. A total of 24 studies from 11 countries were included (Germany (n=3 studies), Australia (n=1), Belgium (n=3), Canada (n=6), the USA (n=2), France (n=2), Japan (n=3), the Netherlands (n=2), the UK (n=1), Sweden (n=2), Switzerland (n=1)) (online supplementary appendix 1).4 5 10–31 Sampling was done by wiping the containers (n=20) or by immersion (n=3). Liquid chromatography tandem-mass spectrometry (n=15) and gas chromatography tandem-mass spectrometry (n=15) were mostly used to quantify the drugs.
ejhpharm-2018-001705supp001.pdf (293.7KB, pdf)
Sixteen different drugs were quantified on the exterior of commercial drug containers (table 1). Twenty-eight manufacturers were identified. The majority (2379/4248, 56%) of containers had antineoplastic drugs traces on them. A maximum of 150 000 ng was measured on a glass vial of fluorouracil. Contamination differed per type of container. All blister packaging sampled were contaminated, while no plastic vial or ampoules were contaminated (online supplementary table). There was no clear reduction in the proportion of positive containers over the years for the three most frequent drugs (online supplementary figure).
Table 1.
Contamination found on the exterior of commercial vials per drug
| Drug (n studies) | Manufacturers (n) | Positive containers (n/N (%)) | Maximum concentration (ng/vial) |
| Cyclophosphamide (n=15) | 5 | 545/967 (56.4%) | 69 819 |
| Cytarabine (n=1) | 2 | 4/11 (36.4%) | 32.35 |
| Docetaxel (n=1) | 1 | 33/33 (100%) | ND |
| Doxorubicin (n=2) | 6 | 73/91 (80.2%) | 4.05 |
| Epirubicin (n=1) | 5 | 3/15 (20%) | 17.3 |
| Etoposide (n=2) | 3 | 204/207 (98.6%) | 1890.6 |
| Fluorouracil (n=7) | 6 | 386/727 (53.1%) | 150 000 |
| Gemcitabine (n=1) | 5 | 3/15 (20%) | 3.54 |
| Ifosfamide (n=6) | 3 | 300/901 (33.3%) | 1705 |
| Irinotecan (n=1) | 7 | 7/27 (25.9%) | 145.14 |
| Methotrexate (n=6) | 4 | 22/146 (15.1%) | 15 000 |
| Platinum* (n=9) | 9 | 799/1099 (72.7%) | 4719 |
| Vincristine (n=1) | 2 | 0/9 (0%) | ND |
*Carboplatin, cisplatin and oxaliplatin were grouped.
ND, not determined.
ejhpharm-2018-001705supp002.pdf (210.3KB, pdf)
ejhpharm-2018-001705supp003.pdf (87.6KB, pdf)
Discussion
Twenty-four studies published between 1992 and 2014 were identified. The contamination of the exterior of commercial antineoplastic drug containers was widespread. There was no definite sign of improvement over the years. Contamination was observed on many types of containers, from different manufacturers and in all countries.
The contamination of containers should be taken seriously by healthcare centres since a contaminated container can cross-contaminate the receipt area, the hands and gloves of workers handling them and the subsequent storage areas. Hazardous drugs should be segregated in storage areas to limit cross-contamination. We advocate for a thorough cleaning of the containers before they exit the production and are sent to the sites. Commercial protective overwrap can theoretically reduce this risk, but the protective wrapping itself was found to be contaminated.15 25 27 Protective wrapping added during the manufacturing process may contribute to a false sense of safety and they should be handled with the same precautions as other antineoplastic drug containers. Hospital workers may also discard the secondary container and clean the vials on receipt, when possible.32 Workers performing drug receipt or handling antineoplastic drug vials should definitely wear gloves .
Footnotes
Contributors: DH, CT and J-FB contributed to the initial design of the work, analysed the data and approved the final version to be published. DH drafted the first version of the manuscript. CT and J-FB revised the manuscript and wrote the final draft.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
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Associated Data
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Supplementary Materials
ejhpharm-2018-001705supp001.pdf (293.7KB, pdf)
ejhpharm-2018-001705supp002.pdf (210.3KB, pdf)
ejhpharm-2018-001705supp003.pdf (87.6KB, pdf)