Safety

7. Safety

Antineoplastic agents are potentially hazardous and must be handled with caution. While the risks associated with BCG and MMC differ, given that BCG is an attenuated vaccine and MMC is a cytotoxic drug, only MMC is listed as hazardous drug on the National Institute for Occupational Safety and Health (NIOSH) Alert List of the United States government public health agency the Centers for Disease Control (CDC). These substances have the potential to cause carcinogenic effects, developmental or reproductive toxicity and organ damage [24].

7.1 European safety regulations

The European Agency for Safety and Health at Work (EU-OSHA) aims to minimise any risk of mutagenic exposure to the population. European regulations are implemented within individual EU Member States, with each Member State responsible for developing local regulations based on the EU directive [25]. In the United States, healthcare worker safety is governed by the Occupational Safety and Health Administration (OSHA) [26].

To protect workers from exposure to carcinogenic toxins, the European Council issued a directive indicating the minimum safety requirements [27]. The directive makes the following recommendations (Article 5):

Reduce sources of exposure: Use a biological safety cabinet when possible. It is at the discretion of the management/staff whether a closed system is to be used in accordance with the risk assessment performed and relevant legislation. The technical measures that are used should also be validated with appropriate monitoring techniques
Evacuation of carcinogens at the source by local extraction or general ventilation: The use of clean rooms with biological safety cabinet or isolators when a closed system for the medication is not used
Individual protection measures (personal protective equipment/PPE): The use of gloves, gowns, masks and protective clothing

Prevention against exposure is the highest goal to strive for when working with hazardous medication. The National Institute for Occupational Safety and Health in the United States also recommends that a closed system be used throughout the hazardous drug-handling chain, from pharmaceutical compounding to patient dose administration [28].

7.2 Risk factors and exposure

Both BCG and MMC pose significant health risks to individuals who are exposed to them during handling. These hazardous drugs are highly toxic, and as such, no permissible

exposure level has been established for them [29]. Research on occupational exposure has revealed that healthcare workers, particularly oncology nurses, face the highest risk of exposure to these drugs. These nurses, who are frequently exposed to carcinogenic agents, are at an increased risk of developing leukaemia, other cancers, genetic mutations and reproductive health issues, including miscarriages, infertility and congenital abnormalities. This heightened risk underscores the critical need for stringent safety protocols to protect healthcare workers from accidental exposure to these potent carcinogens [30-37].

Employers must assess the risk of handling antineoplastic and biological drugs and take suitable precautions to protect employees by identifying the hazards and deciding who might be harmed and how. Exposure during handling of BCG and MMC may be through skin absorption, eye contact, inhalation of aerosols and drug particles, ingestion and needle stick injuries during drug preparation and administration, handling of patient waste, transport and waste disposal, and cleaning of spillages.

People at risk of contamination include:

Transporters of the medication before and after preparation
Healthcare professionals: pharmacists/pharmacy assistants, nurses/nurses’ assistants, operating room theatre technicians and doctors
Cleaning personnel
Handlers of waste
Handlers of linen/bedding
Patients
Family members/people close to the patient

7.3 Risks during drug preparation

Spillage of medication often occurs at the connection points of syringes, tubes (such as infusion sets) and urinary catheters.

Measures to reduce exposure during sterile preparation should include the use of needle-free systems whenever possible. When needle-free systems are not feasible, appropriate precautions should be taken, such as using syringes with Luer-lock connections - commonly used to ensure a secure attachment that minimises the risk of needle or tube slippage and leakage. Additionally, air-venting devices should be utilised to reduce the aerosolization of hazardous drugs, which can pose an increased risk to the individual preparing MMC and BCG.

Additional precautions include the following [25]:

If a closed system is not available, use a biological safety cabinet for preparation.
Purge preparations with dissolvent.
Use an impermeable, single-use, waterproof mat with the absorbent side up.
Use appropriate personal protective equipment (PPE).

7.4 Risks during drug administration

The risk of spillage during instillation can occur as follows:

Contamination of the exterior of the system due to spillage during reconstitution within the biological safety cabinet
Spillage of medication prior to catheter insertion into the bladder
Spillage around the catheter caused by a bladder spasm
Potential spillage of medication remaining in the catheter upon removal
The patient’s inability to retain the medication for the prescribed dwell time or experiencing incontinence

7.5 Risks when handling patient waste

All material that has been exposed to medication used in intravesical instillation should be considered contaminated and disposed of in accordance with local and hospital regulations in a container specifically used for chemotherapeutic waste [38].

Single use items include:

Disposables
Syringes
Tubing
Packaging material
Catheters
Cleaning tissues
Absorbent pads
Incontinence pads
Personal protective equipment (PPE)

Reusable items include:

Linens contaminated with MMC or BCG, or excreta from patients who have received intravesical instillations in the past two days are potential sources of occupational exposure. Linens soiled with blood or other potentially infectious materials, as well as excreta, must also be managed as contaminated material. Linens contaminated with MMC or BCG should be placed in specially marked impervious laundry bags. Contaminated laundry should be washed separately from other laundry and preferably washed twice (cold and warm), following a two-step washing procedure [26, 38, 39].
The mattress of the gurney or bed used during the intravesical instillation should be protected from contamination using protective absorbent pads [40].

7.6 Risks during transportation

During transportation, drug contamination might occur due to damage to the vial/ container or contamination of the exterior of the package after preparation. During transportation, the handling personnel must be aware of the content and the risks involved. In accordance with local regulation, a sign/label can be used. Special signage should be used to alert those present in the same room in which hazardous drugs are stored or used [26, 40].

7.7 Cleaning and management of spillages

Periodic cleaning of work surfaces and areas with appropriate deactivation agents according to local guidelines before and after each patient encounter should be part of the established practice of each clinic/hospital.

Deactivation agents are listed on the Material Safety Data Sheet for each manufacturer [41].

Clean-up of small spills
Safety procedures should be in place in any area involved with handling hazardous drugs. Small spills are considered to be < 5ml.

Spills < 5ml or < 5g outside a biological safety cabinet must be cleaned up immediately by personnel wearing gowns, double latex gloves and splash goggles. If latex gloves are against national regulations or in cases in which the healthcare worker and/or patient has allergies, chemotherapy nitrile/neoprene single gloves should be used.
Liquids should be removed with absorbent gauze pads and solids should be wiped with wet absorbent gauze. The spill areas should then be cleaned three times using a detergent solution followed by clean water.
Any broken glass fragments should be picked up using a small scoop (never by hand) and placed in a sharps container. The container should then be placed in a hazardous drugs disposal bin, along with used absorbent pads and any other contaminated waste.
Contaminated reusable items, such as glassware and scoops, should be treated as outlined previously in the subsection on reusable items [26].

Clean-up of large spills
Safety procedures should also be in place for large spills, which are > 5ml.

Large spill areas should be isolated, avoiding aerosolisation of the drug.
Spills should be handled by personnel properly trained in the handling of hazardous material.
Cover liquid spills with an absorbent pad/sheet.
Protective apparel, including respirators, should be used as with small spills when there is any suspicion of airborne powder or that an aerosol has been or will be generated.

All contaminated surfaces should be thoroughly cleaned three times with detergent and water. All contaminated absorbent sheets and other materials should be place in a disposal bag for hazardous drugs [26].