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Hazardous drugs and eliminating contamination

Cytotoxic and hazardous drug compounding is a technical challenge because it is necessary to implement correct aseptic technique to maintain product sterility while also minimising potential occupational and environmental exposure owing to the deleterious effects of this class of drugs.1

Healthcare personnel are also in danger of exposure to hazardous drugs and their effects at all contact points, including point of manufacture, transport, distribution, receipt, storage, preparation, administration, and waste handling. Pharmacists and nurses risk particular exposure to cytotoxic agents during preparation and administration.

What is considered hazardous?
Drugs that meet one or more of the following criteria should be handled as hazardous:

  • Carcinogenicity
  • Teratogenicity or developmental toxicity
  • Reproductive toxicity
  • Organ toxicity at low doses
  • Genotoxicity
  • Structure or toxicity similar to drugs classified as hazardous using the above criteria.

Harmful effects from workplace exposure to these agents were first described in the 1970s by Falck and colleagues.2 Risks associated with handling of these agents include mutagenesis and damage to DNA, and a possible increase in the risk of cancer and infertility.3–8

Routes of exposure
The most commonly identified routes of exposure and contamination are absorption through direct skin contact, inhalation, ingestion, and needlestick injuries.

Personal protective equipment
The use of personal protective equipment (PPE) when handling hazardous drugs has been recommended since the 1980s by The Occupational Safety and Health Administration (OHSA). PPE for hazardous drug handling includes:

  • Gowns – disposable, made of fabric that has low-permeability to the agents in use, with closed-front and cuffs, intended for single use
  • Gloves – powder-free, labelled and tested for use with chemotherapy drugs, made of latex, nitrile, or neoprene
  • Face and eye protection when splashing is possible
  • A respirator when there is a risk of inhaling drug aerosols.

Safety standards and guidelines
As awareness of the routes of exposure increased, safety standards have been published from technical institutes and professional bodies. These include: Occupational Safety and Health Administration, 19999National Institute for Occupational Safety and Health (NIOSH), 200410
United States Pharmacopeia USP 79711 American Society of Health System Pharmacists, 200612 Infusion Nurses Society, 200613 and International Society of Oncology Pharmacy Practitioners, 2007.14

A newer proposed standard – USP 800 – is to provide standards to protect personnel and the environment when handling hazardous drugs and is intended to define processes to provide containment of hazardous materials to as low a limit as possible (

Demonstrating contamination
Observational studies have demonstrated surface contamination with these agents, and contamination outside of the preparation area/biological safety cabinet,15–17 and workers are likely to come in to contact with contaminated surfaces when not wearing PPE. The presence of hazardous drugs in the urine of healthcare workers has also shown that systemic absorption is a possibility, as shown by Sessink and colleagues in 1992.18

A study by Boccellino and colleagues has also demonstrated that doxorubicin can penetrate nitrile gloves.19

Minimising any environmental contamination is therefore vital to safeguard healthcare professionals against exposure to hazardous drugs.

Closed system transfer devices
Closed system transfer devices are playing an increasing role as part of the approach to reduce exposure of personnel to hazardous agents.

A closed-system transfer device is defined as: a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system. The system must be airtight and leakproof. 10,14 Both the NIOSH and USP 797 standards recommend the use of CSTDs, in conjunction with PPE, when preparing and administering chemotherapy.

Studies have demonstrated the effectiveness of CSTDs in decreasing surface contamination and reducing exposure. Siderov and colleagues20 performed a pre- and post-intervention study in which chemical contamination was tested at baseline, five and 12 months after the introduction of a CSTD. Cyclophosphamide was used as a surrogate marker for all cytotoxic drugs. After five months, contamination was reduced in 13 of the 22 sites sampled with four of these samples showing undetectable levels of contamination. After 12 months, surface contamination was reduced in 75% of sample sites. The total contamination of surfaces tested was reduced by 68%.

Sessink and colleagues published data from a study of 22 US hospital pharmacies showing that the implementation of a CSTD reduced surface contamination significantly.21 Using a CSTD compared with the standard preparation techniques resulted in a significant reduction in levels of surface contamination for all drugs tested (cyclophosphamide, isosfamide and 5-Fluorouracil (5-FU); 95%, 90% and 65%, respectively).

Evaluating a CSTD in the workplace setting is important to validate the effectiveness of the product. A study by Sessink and Clark22 evaluated the effectiveness of the EquaShield CSTD in an ambulatory cancer chemotherapy infusion centre between June 2010 and August 2011.22The cancer centre has approximately 16,500 chemotherapy visits per year and has a dedicated pharmacy for chemotherapy preparation.

The system
The Equashield system comprises a double-membrane for drug transfers and a two-chambered syringe (having a distal chamber for air and a proximal chamber for liquid), which is airtight. The connector has dual needles to allow for air and liquid exchange.

Methods and results
Twelve areas were tested for contamination with cyclophosphamide and 5-FU: within the pharmacy, infusion areas and offices. Initial wipe sampling results demonstrated environmental contamination with cyclophosphamide in a number of departments. One site was contaminated with 5-FU, which might be a result of the higher detection limit for the analysis of 5-FU compared with cyclophosphamide.

The final sampling results were obtained one year after implementation of the CSTD and demonstrated a contamination-free environment. Implementation of the CSTD had eliminated surface contamination at the ambulatory infusion centre.22

In combination with other personal protective measures, CSTDs can prevent leakage or accidental discharges during and after administration of chemotherapeutic agents and hazardous drugs, thereby protecting healthcare staff from accidental exposure.


  1. Connor TH et al. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin 2006;56(6):354–65.
  2. Falck K et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250–1.
  3. Valanis B et al. Acute symptoms associated with antineoplastic handling among nurses. Cancer Nurs 1993;16:288–95.
  4. Valanis B et al. Occupational exposure to antineoplastic agents and self-reported infertility among nurses and pharmacists. J Occup Environ Med 1997;39:574–80.
  5. Skov T et al. Leukaemia and reproductive outcomes among nurses handling antineoplastic drugs. Br J Indust Med 1992;49:855–61.
  6. McDiarmid MA et al. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med 2010;52(10):1028–34.
  7. Dranitsaris G et al. Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature. J Oncol Pharm Pract 2005;11(2):69–78.
  8. Hansen J et al. Cancer morbidity among Danish female pharmacy technicians. Scand J Work Environ Health 1994;20(1):22–6.
  9. Occupational Safety and Health Administration. Technical manual, 1999. TED 1-0.15A, Section VI, Chapter 2.
  10. National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings.
  11. The United States Pharmacopeial Convention. USP 797 Guidebook to pharmaceutical compounding-sterile preparations;2008.
  12. ASHP (American Society of Health System Pharmacists). Guidelines on handling hazardous drugs. Am J Health Syst Pharm 2006;63:1172–93.
  13. Infusion Nurses Society. J Infus Nurs 2006;29(1 Suppl):S1–92.
  14. International Society of Oncology Pharmacy Practitioners Standards Committee. ISOPP standards of practice. Safe handling of cytotoxics. J Oncol Pharm Pract 2007;13 Suppl:1–81.
  15. Hedmer M et al. Environmental and biological monitoring of antineoplastic drugs in four workplaces in a Swedish hospital. Int Arch Occup Environ Health 2008;81(7):899–911.
  16. Sessink P et al. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl (Sci) 1992;14:16-22.
  17. Connor TH et al. Surface contamination with antineoplastic agents in six cancer centers in Canada and the United States. Am J Health Syst Pharm 1999;56:1427–32.
  18. Sessink PJ et al. Occupational exposure to antineoplastic agents at several departments in a hospital. Environmental contamination and excretion of cyclophosphamide and ifosfamide in urine of exposed workers. Int Arch Occup Environ Health 1992;64(2):105–12.
  19. Boccellino M et al. Doxorubicin can penetrate nitrile gloves and induces apoptosis in keratinocyte cell lines. Toxicol Lett 2010;197:61–8.
  20. Siderov J et al. Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Pract 2010;16(1):19–25.
  21. Sessink P et al. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract 2010;17:39–48.
  22. Clark B, Sessink P. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract 2013;19(2):99–104.

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