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Safe handling of cytotoxic drugs

Occupational exposure to cytotoxic drugs in hospital pharmacies remains a significant issue for those potentially exposed and those responsible for their health and safety. This article is written not from a pharmacist’s viewpoint, but from within the wider context of risks from cytotoxics, and from the viewpoint of the UK regulatory body, the Health and Safety Executive (HSE), which has responsibility for occupational health and safety. In this context the control of risks from cytotoxics in hospital pharmacies can be viewed against how other UK workplaces control the risks from toxic chemicals.

Concerns for healthcare workers
Concerns about risk to health from occupational exposure to chemotherapeutic drugs (“cytotoxics” in this article) are not new. Such drugs are hazardous because of their high toxicity, and occupational exposure may involve a cocktail of drugs. It is not only pharmacy staff who are potentially exposed to cytotoxics. However, pharmacies have been an international focus of investigation. Centralisation of cytotoxic preparation, for cited reasons of a safer controlled environment, means that large amounts of cytotoxics are stored and formulated by a relatively small number of staff. One factor that distinguishes the hospital pharmacy from other workplaces using highly toxic chemicals is that control measures are needed both for protection of staff and maintenance of product sterility.

Main discussion
The primary adverse health outcomes from cytotoxics are cancer and a range of poor reproductive outcomes, which are particularly relevant as most staff involved in UK cytotoxic preparation are female and of reproductive age.(1) Occupational epidemiology can be uninformative, with any discovered risk of ill-health reflecting past, outdated work practices. A recently published meta-review covering published data from 1966 to 2004 was only able to show a small (OR = 1.46) increased risk of spontaneous abortions for “female staff working with �cytotoxic drugs”.(2) Currently there is no clear evidence on the quantitative level of increased health risks, if any, to pharmacy staff working with cytotoxics under typical UK conditions.

The UK generic legislation Control of Substances Hazardous to Health (COSHH, 1994) applies to cytotoxics in pharmacies and has been in place, with amendments, since 1994 (see Resources).(3) Given the toxic nature of cytotoxics and the lack of any evidence of safe exposure levels, HSE’s general strategy is that the risks (ie, exposure) must be reduced to “as low as reasonably practical”. This implies some balance between expenditure and benefits, but acknowledges that changes in knowledge and technology may necessitate further exposure reduction. Such risk reduction should be done against an understanding of where and how exposure to cytotoxics may occur, and the general hierarchy of measures to control such exposure (see Figure 1).

Clearly substitution (B) and complete elimination of the hazard (A) cannot be applied as control measures. The most effective control measure then is barrier engineering control (C). A recent report on UK pharmacies1 suggested that more than 86% of units preparing cytotoxics are now using high-containment isolator technology, with only 5% relying on vertical laminar flow cabinets and/or microbiological safety cabinets; this situation may not be matched in other countries.(4,5) However, even with the use of isolators, some external surface contamination has been reported.(6,7) Devices to control aerosol formation from reconstitution of lyophilised drugs(8,9) and using drugs supplied in liquid form are useful means of reducing the hazard.

The low-level contamination found outside isolators may reflect that found on some vials and �packaging delivered to pharmacies,(10,11) the effects of vial handling and sanitisation procedures. However, an alternative source of such contamination may relate to the reported volatilisation of some cytotoxics produced as small particles within aerosols,(12) and air filtered using high-efficiency particulate air (HEPA) systems that was recirculated to the room might not remove such vapours.

The likely levels of any vapour-phase cytotoxics under normal work practices need some investigation. Contaminated primary product and packaging highlight the need for appropriate protection of stores staff. This would largely rely on gloves as personal protective equipment (PPE) to prevent dermal exposure, plus training and raising risk awareness. Such PPE use does not appear widespread in the UK.(1)

External surface contamination, even when using high-containment enclosures, has also raised issues about cleaning procedures. Further research has been proposed to investigate cleaning agents and strategies for cytotoxic removal and their chemical degradation, if possible. Some current cleaning strategies for floors and work surfaces may reduce microbiological contamination but effectively spread any localised cytotoxic contamination.

Use of guidance and PPE as control measures (D and E in Figure 1) are considered to be of lower effectiveness because they rely on staff compliance. Guidance produced over the years by various national regulatory, professional and specialist bodies (see Resources) can generally be presumed to be positive in promoting safer environments. However, there is evidence from many work sectors, including hospitals, that guidance, especially regarding PPE usage, is not always followed.(13) Poor usage of disposable gloves can increase dermal uptake, so training and policies on glove usage are important. Gloves marketed for specific use with cytotoxics, including some independent test data, have been available for some time.(14) However, general disposable gloves are widely used, and it is interesting that data on the time-dependent permeability of different materials against specific drugs, and under dynamic usage, is still being produced.(15)

Within the HSE strategy for controlling toxic hazards, the last element would be to monitor and review the effectiveness of any implemented controls. Annual health surveillance(16) for those working with cytotoxics is common in the UK, but there is currently no accepted biological test to help identify the early effects of any cytotoxic absorption. Sensitive urine measurements are able to detect widely used drugs (cyclophosphamide, ifosfamide, the platino-coordinated, methotrexate and anthracyclins) and can be used after actual or suspected exposure, or as part of regular monitoring to monitor any uptake. A significant number of environmental monitoring research studies from several countries(5) have been published. Albeit with some concerns about the intercomparability of the data, they do indicate that some structured surface monitoring can be useful for benchmarking the efficacy of existing control measures and reviewing the effects of modifying any work practices.

Lack of any identifiable safe exposure level means that responsible management can only ensure that the risk of exposure is reduced to as low as practically possible.

Appropriate control measures in the pharmacy need to address the whole workflow, from delivery from manufacturer to supply of prepared drugs to wards and/or outpatients. In HSE’s hierarchy of control this means using high-level containment for formulation, implementing practical measures or work practices that separate drug and staff, and use of appropriate PPE to reduce the residual risk of dermal absorption. Procedures for cleaning and maintenance of facilities should relate to cytotoxic removal or degradation.

There may be a role for some monitoring strategies to establish the effectiveness of the applied control measures in a pharmacy. HSE is hoping to undertake soon a cross-sectional monitoring study to help benchmark current likely exposure to staff in UK pharmacies and also allow some comparison with similar internationally collected data.


Howard Mason
Principal Scientist
Health and Safety Laboratory
Harpur Hill
E: [email protected]


  1. Mason H. Questionnaire study of hospital pharmacy units undertaking antineoplastic drug preparation. HSL Report Series HE 05/01. Health and Safety Laboratory; 2005.
  2. Dranitsaris G, et al. J Oncol Pharm Pract 2005;11(2):69-78.
  3. Health and Safety Executive. Control of �substances hazardous to health. HSE Books;2005. p. 1-144.
  4. Schreiber CK, et al. Int Arch Occup Environ Health 2003;76:11-6.
  5. Turci R, et al. J Chromat B 2003;789:169-209.
  6. Crauste-Manciet S, et al. Ann Occup Hyg 2005;49(7):619-28.
  7. Mason H, et al. Ann Occup Hyg 2005;49(7):603-10.
  8. Clark C. Pharmaceut J 1999;263:65-8.
  9. Wick C, et al.Am J Health-Syst Pharm 2003;60(22):2314-20.
  10. Mason H,et al. Ann Occup Hyg 2003;47(8):681-5.
  11. Nygren O, et al. Ann Occup Hyg 2002;46(6):555-7.
  12. Kiffmeyer T,et al. Pharmaceut J 2002;268:331-7.
  13. Nieweg R, et al.Cancer Nurs 1994;17(6):501-11.
  14. Singleton L,Connor T. Oncol Nurs Forum 1999;26(9):1491-6.
  15. Wallemacq P, et al. Am J Health-Syst Pharm 2006;63(6):547-56.
  16. DesRoches P. AAOHN 2003;51(3):106-8.

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