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Published on 1 November 2005

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External contamination of antineoplastic drug vials

teaser

Thomas H Connor
PhD
Research Biologist
National Institute for Occupational Safety and Health
Cincinnati, OH
USA
E:tmc6@cdc.gov

Several factors have contributed to the potential for increase in exposure of healthcare workers to antineoplastic and other hazardous drugs. These include increasing numbers of patients with cancer and other chronic illnesses, the use of higher doses of drugs (made possible by strategies to reduce the toxic side-effects of the drugs), noncancer use of antineoplastic drugs and the development of other potent drugs, such as antiviral agents. Because it has been well documented over the past 20 years that healthcare workers, especially pharmacists and nurses, are exposed to these drugs in the workplace, government institutions and professional organisations around the world have developed guidelines for the safe handling of antineoplastic and other hazardous drugs. In the USA, the National Institute for Occupational Safety and Health (NIOSH)(1) recently published an alert that lists recommendations for the safe handling of all hazardous drugs, of which antineoplastic drugs are the major class. Others classes of hazardous drugs include some hormonal, ­immunosuppressive and antiviral agents, monoclonal antibodies and several miscellaneous drugs.

Reports from Europe and the USA have shown that most surfaces in hospital pharmacies and patient treatment areas are contaminated with one or more of the antineoplastic drugs that are commonly used to screen for workplace contamination. These drugs include cyclophosphamide, ifosfamide, fluorouracil methotrexate, doxorubicin and platinum-containing compounds. Surface wipe samples have been developed to recover ­antineoplastic drugs from various surfaces in the hospital setting. Sensitive techniques have been developed to analyse for these marker drugs.(2) However, such a strategy can only estimate the overall level of contamination with hazardous drugs, since several dozen or more drugs can be used in any one location.

Studies examining airborne concentrations of antineoplastic drugs in pharmacies and treatment areas have usually demonstrated low concentrations in a small percentage of the samples. Given the physical nature of most antineoplastic drugs (eg, powder or liquid), airborne concentrations may not be the major route of exposure for these drugs. However, aerosols may produce airborne particulates that could be inhaled or deposited on work surfaces. Based on the widespread contamination of work surfaces such as the inside of biological safety cabinets (BSCs), floors, counter tops, trays, IV bags or patient chairs, the dermal route appears to be the major source of exposure to these drugs. Hand-to-mouth exposure may also occur from poor work practices, such as having food or drink in or near areas where antineoplastic drugs are stored, prepared or administered.

Reducing surface contamination
Routine handling procedures can result in the release of drugs to the work environment. Several factors can play a role in reducing this release and in reducing worker exposure to the drugs:

  • Proper training.
  • Use of approved preparation and administration techniques.
  • Use of BSCs and/or isolators.
  • Proper use of approved personal protective equipment.
  • Use of supplemental containment devices.
  • Proper cleaning and disposal of waste materials.

Over the past few years, European studies have shown that external surfaces of antineoplastic drug vials are often contaminated with the drugs that are contained within the vials. Vials for a number of drugs from several different manufacturers are contaminated with the drugs. A recent study from two pharmacies in the USA and one manufacturing facility in Europe supports the previously reported data on antineoplastic drug vial contamination.(3) Antineoplastic drug vials were sampled from the National Institutes of Health (NIH) Clinical Center pharmacy and the Veterans Affairs (VA) Medical Center pharmacy. Vials at the NIH were assayed for contamination with cyclophosphamide and ifosfamide, and those at the VA were assayed for contamination with cyclophosphamide and fluorouracil. Vials from a facility in Europe where cisplatin is manufactured were assayed for platinum following various approaches of decontamination and covering the vials with a plastic film.

In the US study, vials were sampled from ­different lot numbers and from different manufacturers. One hundred percent of the cyclophosphamide vials sampled at the NIH and 89% of those from the VA had measurable concentrations of the drug on the outside of the vials. Some vials of cyclophosphamide from the NIH demonstrated concentrations as high as 70µg per vial. Six ifosfamide vials from one manufacturer had concentrations of 1.5–1.7µg per vial. The vials from a second manufacturer had little to no detectable concentrations on the vials. Although fluorouracil was found on only 7% of the vials from the VA, one had a concentration of 630µg per vial. In both studies, no evidence of contamination from vial breakage was observed. It is obvious that, if a healthcare worker were to handle a number of similarly contaminated vials without the proper gloves and respiratory protection, substantial dermal and possible inhalation exposure could occur. In a follow-up study of the NIH vials, it appears that lyophilised drugs have higher concentrations of drug contamination on a higher percentage of vials tested.(4) This suggests that the lyophilisation process may contribute to vial contamination. The investigation of cisplatin contamination in the manufacturing facility demonstrated that improved vial cleaning, especially in combination with covering the filled vial with a plastic film, can reduce external contamination on drug vials. However, some level of contamination was still detected on a percentage of the vials, even with more rigorous cleaning and/or the addition of the plastic film. Because concordant findings in Europe and the USA have demonstrated that vial contamination with antineoplastic drugs is quite common and that levels of contamination can be substantial, drug vials should always be handled as if they pose a health hazard to the worker. Even if all other safe handling precautions and recommendations are followed in a facility where antineoplastic drugs are present, there still exists the potential for environmental contamination and possibly worker exposure to these drugs to occur from contaminated vials.

Disclaimer:
The findings and conclusions of this report have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy

References

  1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings 2004. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No 2004-165.
  2. Turci R, Sottani C, Spagnoli G, et al. Biological and environmental monitoring of hospital personnel exposed to antineoplastic agent: a review of analytical methods. J Chromatog B Analyt Technol Biomed Life Sci 2003;789:169-209.
  3. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health-Syst Pharm 2005;62:475-84.
  4. Connor TH, DeChristoforo R, Pretty JR, et al. External contamination of chemotherapy drug vials. 10th Congress of the European Association of Hospital Pharmacists. Lisbon, Portugal, March 2005.

Resource
NIOSH Alert: Preventing occupational exposures to
antineoplastic and other hazardous drugs in health care settings.
W:www.cdc.gov/niosh/docs/2004-165/



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