Cytotoxic handling and the importance of appropriate gloving

Since 1999 there has been continuous international interest in the safety aspects of handling cytotoxic agents, following the publication of several studies on the health risk associated with occupational exposure to cytotoxic agents, especially with focus on the reproductive effects.(1-9)

International organisations, such as the IARC (International Agency for Research on Cancer), have divided several commonly used cytotoxic drugs into two categories: “proven carcinogenic” and “probably carcinogenic”.

Increasing chemotherapy workload with more and higher dosages and newer, more potent drugs in the therapy arsenal brings this item to a higher level of anxiety for the staff who have to prepare and administer the drugs.

Safety level
The European directive to protect people against carcinogenic agents at work is very clear in the way these products should be handled. One should follow a hierarchical order in prevention:

• Level 1 is to replace the product by a less toxic or nontoxic one.
• Level 2 is the use of closed systems. This means isolation of the hazard or source containment. By containing the product throughout the entire process of preparation and administration at its source, the contamination of persons or materials is prevented. The US National Institute for Occupational Safety and Health (NIOSH) described this as a closed system for drug transfer – in other words, a device that mechanically prohibits the transfer of environmental contaminants into the system and prevents the escape of hazardous drugs or vapour concentrations outside the system. According to the definition of the International Society of Oncology Pharmacy Practitioners (ISOPP) standards committee, this means “leakproof and airtight” to prevent the occurrence of any form of contamination.(10-15)
• Level 3 is the use of local and general ventilation measures. The opinion of the ISOPP standards committee is that isolators and biological safety cabinets (BSC) fit in the level 3 category under the conditions that they are well engineered, controlled and validated.
• Level 4 is the use of personal protection measures.

Although personal protection is the lowest level in the hierarchical structure of the safety procedures, it remains essential for daily practice. Gloving has a particularly important place within level 4 because gloving can help us to protect ourselves against cytotoxic drug contact, while enabling us to protect the drug from particular and microbiological contamination.

Cytotoxic gloves

Sterile gloves used for preparations
The label “cytotoxic glove” cannot be accepted without the necessary tests and validation. Several critical points have to be considered:

• Temperature. Tom Connor indicated during the Gerpac Congress 2005 that the temperature of the glove rises to 34C after only five minutes, and traditional testing is done at temperatures of 25C. Higher temperatures could increase the permeation rate of certain products by a factor of at least two.
• Static/dynamic testing method. The purpose of a glove is to use it, meaning that we will stretch and rub the glove while using it. Until now, all studies, including the ones performed within the context of the European applicable norm (EN374-3),have been — and still are — performed in a static test situation and at room temperatures that probably underestimate the permeation results.(16,17) Permeation levels allowed by the norm are much too permissive, allowing a permeation of 1 mg/cm(2)/minute), and therefore do not guarantee safe handling. In 2005, a new test methodology was developed at the Universite Catholique de Louvain (Belgium) by Pierre Wallemacq and Bertrand Favier. The new methodology, developed in close collaboration with medical glove manufacturer Ansell Ltd, uses a dynamic test method. The test machine mimics the dynamic movements of the hand and can be used with different acceptor media and temperature — for example, a test on the permeation of oxaliplatin at 42 C over a period of 30 minutes, with these conditions being similar to that of a surgeon with his/her hands in the abdomen of a patient during a hyperthermia in combination with surgery and chemotherapy (HYPEC) procedure.(18) Furthermore, different permeation outcomes can result from other factors: the material used for the glove, conditions under which it was manufactured, products added during manufacture, and the drug’s molecular weight and lypophilic properties. Assumptions and extrapolations cannot be made, and each kind of glove should be tested.

Nonsterile gloves
It has long been known that the drugs coming into our hospital pharmacy and warehouses are not 100% free of contamination. Although some manufacturers have improved their washing and/or packaging techniques (via overlaid shrink foil, protection containers, etc), many vials are still contaminated.(19-21) In order to protect staff it is advised that they wear gloves with proven resistance at all times when they come into contact with the drug container and/or packaging. If contamination occurs in the protected working zone (isolator/BSC), it will emerge together with the prepared infusion bags or syringes and with the waste. However, some isolators allow users to seal the waste and the prepared products in plastic bags. This is only a temporary solution, because nurses need to unpack it before they can administer the drug to the patient, at which time they come into contact with a diluted form of the drug.(22,23)

The drugs administered to the patient will be metabolised and/or excreted, and again nurses will come into contact with a second dilution of the drug. All forms of excreta should be considered as potentially contaminated (urine, faeces, saliva, but also sweat). Patients themselves are a source of contamination, as shown by wipe samples from patients’ skins.(24,25) Therefore nurses should protect themselves with gloves appropriate for the type of handling carried out (for example, long sleeves) when nursing and washing patients.

Accidents and incidents
Special gloves can be used at certain times — when highly concentrated, large volumes of cytotoxic drugs are spilled or a vial breaks. Special attention should be paid to the possibility of sustaining cuts while removing glass. Thicker gloves with less sensitivity but more resistance are advisable in such cases.

Conclusions
Gloving plays an important role in our daily protection measures, not only in the pharmacy but also, perhaps even more, in the rest of the hospital.

This means that the correct choice and use of gloves, and �providing information to all people concerned, are among the primary jobs of a multidisciplinary cytotoxic hospital workgroup.

Author

Johan Vandenbroucke
PharmD
Senior Pharmacist Production
Central Pharmacy
University Hospital Gent
Belgium
E: [email protected]

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