NIOSH Publication No. 2004-165: Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings	September 2004

RECOMMENDATIONS

Summary of Recommended Procedures

1. Assess the hazards in the workplace.

• Evaluate the workplace to identify and assess hazards before anyone begins work with hazardous drugs. As part of this evaluation, assess the following:
  
  
  • Total working environment
    
    
  • Equipment (i.e., ventilated cabinets, closed-system drug transfer devices, glovebags, needleless systems, and PPE)
    
    
  • Physical layout of work areas
    
    
  • Types of drugs being handled
    
    
  • Volume, frequency, and form of drugs handled (tablets, coated versus uncoated, powder versus liquid)
    
    
  • Equipment maintenance
    
    
  • Decontamination and cleaning
    
    
  • Waste handling
    
    
  • Potential exposures during work, including hazardous drugs, bloodborne pathogens, and chemicals used to deactivate hazardous drugs or clean drug-contaminated surfaces
    
    
  • Routine operations
    
    
  • Spill response
    
    
  • Waste segregation, containment, and disposal
    
    
• Regularly review the current inventory of hazardous drugs, equipment, and practices, seeking input from affected workers. Have the safety and health staff or an internal committee perform this review.
  
  
• Conduct regular training reviews with all potentially exposed workers in workplaces where hazardous drugs are used. Seek ongoing input from workers who handle hazardous drugs and from other potentially exposed workers regarding the quality and effectiveness of the prevention program. Use this input from workers to provide the safest possible equipment and conditions for minimizing exposures. This approach is the only prudent public health approach, since safe concentrations for occupational exposure to hazardous drugs have not been conclusively determined.

2. Handle drugs safely.

• Implement a program for safely handling hazardous drugs at work and review this program annually on the basis of the workplace evaluation. Establish work policies and procedures specific to the handling of hazardous drugs. These policies and procedures should address and define the following:
  
  
  • Presence of hazardous drugs
    
    
  • Labeling
    
    
  • Storage
    
    
  • Personnel issues (such as exposure of pregnant workers)
    
    
  • Spill control
    
    
  • Detailed procedures for preparing, administering, and disposing of hazardous drugs
    
    
• Establish procedures and provide training for handling hazardous drugs safely, cleaning up spills, and using all equipment and PPE properly. Inform workers about the location and proper use of spill kits. Make these kits available near all potential sources of exposure. Make sure that training conforms to the requirements of the OSHA hazard communication standard [29 CFR 1910.1200] and other relevant OSHA requirements such as the PPE standard [29 CFR 1910.132]. In addition, establish procedures for cleaning and decontaminating work areas and for proper waste handling and disposal of all contaminated materials, including patient waste.
  
  
• Establish work practices related to both drug manipulation techniques and to general hygiene practices—such as not permitting eating or drinking in areas where drugs are handled (the pharmacy or clinic).

3. Use and maintain equipment properly.

• Develop workplace procedures for using and maintaining all equipment that functions to reduce exposure—such as ventilated cabinets, closed-system drug-transfer devices, needleless systems, and PPE.

Detailed Recommendations

Receiving and Storage

• Begin exposure control when hazardous drugs enter the facility. The most significant exposure risk during distribution and transport is from spills resulting from damaged containers.
  
  
• Prepare workers for the possibility that spills might occur while they are handling containers (even when packaging is intact during routine activities), and provide them with appropriate PPE.
  
  
• Make sure that medical products have labeling on the outsides of containers that will be understood by all workers who will be separating hazardous from nonhazardous drugs.
  
  
• Wear chemotherapy gloves [ASTM in press], protective clothing, and eye protection when opening containers to unpack hazardous drugs. Such PPE protects workers and helps prevent contamination from spreading if damaged containers are found.
  
  
• Wear chemotherapy gloves to prevent contamination when transporting the vial or syringe to the work area.
  
  
• Store hazardous drugs separately from other drugs, as recommended by ASHP [1990] and other chemical safety standards.
  
  
• Store and transport hazardous drugs in closed containers that minimize the risk of breakage.
  
  
• Make sure the storage area has sufficient general exhaust ventilation to dilute and remove any airborne contaminants.
  
  
• Depending on the physical nature and quantity of the stored drugs, consider installing a dedicated emergency exhaust fan that is large enough to quickly purge airborne contaminants from the storage room in the event of a spill and prevent contamination in adjacent areas.

Drug Preparation and Administration

Initial steps

• As part of the hazard assessment described earlier, evaluate and review the entire drug preparation and administration process to identify points at which drugs might be released into the work environment. Always consider the possibility of contamination on the outside of containers [Ros et al. 1997; Hepp and Gentschew 1998; Delporte et al. 1999; Nygren et al. 2002; Favier et al. 2003; Mason et al. 2003].
  
  
• Limit access to areas where drugs are prepared to protect persons not involved in drug preparation.
  
  
• Coordinate tasks associated with preparing and administering hazardous drugs for most effective control of worker exposures.

Preparing hazardous drugs

• Use a ventilated cabinet designed to reduce worker exposures while preparing hazardous drugs (see following section entitled Ventilated Cabinets).
  
  
• Train all staff who use ventilated cabinets to employ work practices established for their particular equipment. The safe use of any control depends on proper work.
  
  
• Practice proper technique and use of equipment.
  
  
• Include initial and periodic assessments of technique in the safety program [Harrison et al. 1996], and verify technique during drug administration.
  
  
• Wear protective gloves and gowns if you are involved in preparation activities such as opening drug packaging, handling vials or finished products, labeling hazardous drug containers, or disposing of waste.
  
  
• Wear PPE (including double gloves and protective gowns) while reconstituting and admixing drugs:
  
  
  • Make sure that gloves are labeled as chemotherapy gloves and make sure such information is available on the box [ASTM in press] or from the manufacturer.
    
    
  • Consider latex-sensitive workers [NIOSH 1997] and remember that a number of glove materials are suitable for protecting workers from antineoplastic drugs [Connor 1999; Singleton and Connor 1999; Klein et al. 2003].
    
    
  • Consider using chemotherapy gloves for hazardous drugs that are not chemotherapy drugs or for which no information is available.
    
    
  • Use double gloving for all activities involving hazardous drugs. Make sure that the outer glove extends over the cuff of the gown [Connor 1999; Brown et al. 2001].
    
    
  • Inspect gloves for physical defects before use.
    
    
  • Wash hands with soap and water before donning protective gloves and immediately after removal.
    
    
  • Change gloves every 30 minutes or when torn, punctured, or contaminated. Discard them immediately in a yellow chemotherapy waste container [ASHP 1990; Brown et al. 2001].
    
    
  • Use disposable gowns made of polyethylene-coated polypropylene material (which is nonlinting and nonabsorbent). These gowns offer better protection than polyethylene gowns against many of the antineoplastic drugs [Connor 1993; Harrison and Kloos 1999]. Make sure gowns have closed fronts, long sleeves, and elastic or knit closed cuffs.
    
    
  • Dispose of protective gowns after each use.
    
    
  • Use disposable sleeve covers to protect the wrist area and remove the covers after the task is complete.
    
    
    
• When drug preparation is complete, seal the final product in a plastic bag or other sealable container for transport before taking it out of the ventilated cabinet.
  
  
• Seal and wipe all waste containers inside the ventilated cabinet before removing them from the cabinet.
  
  
• Remove all outer gloves and sleeve covers and bag them for disposal while you are inside the ventilated cabinet.
  
  
• Wash hands with soap and water immediately after removing gloves.
  
  
• Consider using devices such as closed-system transfer devices, glovebags, and needleless systems when transferring hazardous drugs from primary packaging (such as vials) to dosing equipment (such as infusion bags, bottles, or pumps). Closed systems limit the potential for generating aerosols and exposing workers to sharps. Evidence documents a decrease in drug contaminants inside a Class II BSC when a closed-system transfer device is used [Sessink et al. 1999; Vandenbroucke and Robays 2001; Connor et al. 2002; Nygren et al. 2002; Spivey and Connor 2003; Wick et al. 2003].
  
  
  • Remember that a closed-system transfer device is not an acceptable substitute for a ventilated cabinet and should be used only within a ventilated cabinet.
    
    
  • Use appropriate PPE and work practices even when you are using a closed system.
    
    
• Have pharmacy personnel prime the IV tubing and syringes inside the ventilated cabinet, or prime them in-line with nondrug solutions—never in the patient’s room.

Administering hazardous drugs

• Administer drugs safely by using protective medical devices (such as needleless and closed systems) and techniques (such as priming of IV tubing by pharmacy personnel inside a ventilated cabinet or priming in-line with nondrug solutions).
  
  
• Wear PPE (including double gloves, goggles, and protective gowns) for all activities associated with drug administration—opening the outer bag, assembling the delivery system, delivering the drug to the patient, and disposing of all equipment used to administer drugs.
  
  
• Attach drug administration sets to the IV bag, and prime them before adding the drug to the bag.
  
  
• Never remove tubing from an IV bag containing a hazardous drug.
  
  
• Do not disconnect tubing at other points in the system until the tubing has been thoroughly flushed.
  
  
• Remove the IV bag and tubing intact when possible.
  
  
• Place disposable items directly in a yellow chemotherapy waste container and close the lid.
  
  
• Remove outer gloves and gowns, and bag them for disposal in the yellow chemotherapy waste container at the site of drug administration.
  
  
• Double-bag the chemotherapy waste before removing the inner gloves.
  
  
• Consider double bagging all contaminated equipment.
  
  
• Wash hands with soap and water before leaving the drug administration site.

Ventilated Cabinets

Use of cabinets

• Mix, prepare, and otherwise manipulate, count, crush, compound powders, or pour liquid hazardous drugs inside a ventilated cabinet designed to prevent hazardous drugs from being released into the work environment.
  
  
• Do not use supplemental engineering or process controls (such as needleless systems, glove bags, and closed-system drug transfer devices) as a substitution for ventilated cabinets, even though such controls may reduce the potential for exposure when preparing and administering hazardous drugs.

Selection

• Consult the following document for performance test methods and selection criteria for BSCs: Primary Containment for Biohazards: Selection, Installation and Use of Biological Safety Cabinets, 2nd edition [CDC/NIH 2000].
  
  
• Select a ventilated cabinet depending on the need for aseptic processing. Aseptic technique is important for protecting hazardous drugs from possible contamination. However, it is also important to consider worker protection and to assure that worker safety and health is not sacrificed. Therefore, when asepsis is required or recommended, use ventilated cabinets designed for both hazardous drug containment and aseptic processing. Aseptic requirements are generally regulated by individual State boards of pharmacy [Thompson 2003; USP 2004].
  
  
• When asepsis is not required, a Class I BSC or an isolator intended for containment applications (a “containment isolator”) may be sufficient.
  
  
• When aseptic technique is required, use one of the following ventilated cabinets:
  
  
  • Class II BSC (Type B2 is preferred, but Types A2 and B1 are allowed under certain conditions)
    
    
  • Class III BSC
    
    
  • Isolators intended for asepsis and containment (aseptic containment isolators) [NSF/ANSI 2002; PDA 2001]

Air flow and exhaust

• Regardless of type, equip each ventilated cabinet with a continuous monitoring device to confirm adequate air flow before each use
  
  
• Use a high-efficiency particulate air filter (HEPA filter) for the exhaust from these controls, and where feasible, exhaust 100% of the filtered air to the outside.
  
  
• Install the outside exhaust so that the exhausted air is not pulled back into the building by the heating, ventilating, and air conditioning (HVAC) systems or by the windows, doors, or other points of entry.
  
  
• Place fans downstream of the HEPA filter so that contaminated ducts are maintained under negative pressure.
  
  
• Do not use a ventilated cabinet that recirculates air inside the cabinet or exhausts air back into the room environment unless the hazardous drug(s) in use will not volatilize (evaporate) while they are being handled or after they are captured by the HEPA filter. Information about volatilization should be supplied by the drug manufacturer (possibly in the MSDS) or by air-sampling data.
  
  
• Seek additional information about placement of the cabinet, exhaust system, and stack design from NSF/ANSI 49–2002 [NSF/ANSI 2002]. Incorporate their recommendations regardless of the type of ventilated cabinet selected.

Maintenance

• Identify a safety and health representative familiar with potential drug exposures and their hazards. Ask that person to review in advance all maintenance activities performed on ventilated cabinets and exhaust systems associated with hazardous drug procedures.
  
  
• Develop a written safety plan for all routine maintenance activities performed on equipment that could be contaminated with hazardous drugs.
  
  
• Properly install and maintain and routinely clean any Class II BSC.
  
  
  • Field-certify its performance (1) after installation, relocation, maintenance repairs to internal components, and HEPA filter replacement, and (2) every 6 months thereafter [NSF/ANSI 2002; OSHA 1999].
    
    
  • Prominently display a current field-certification label on the ventilated cabinet [NSF/ANSI 2002].
    
    
• Treat other types of ventilated cabinets similarly with regard to care and frequency-of-performance verification tests.
  
  
• Select the appropriate performance and test methods for isolators, depending on the type (containment-only or aseptic containment), the operating pressure (positive or negative and designed magnitude), and the toxicity of the hazardous drug:
  
  
  • At a minimum, provide isolators with a leak test and a containment integrity test such as those described in Guidelines for Gloveboxes [AGS 1998].
    
    
  • Perform a HEPA filter leak test (described in NSF/ANSI [2002]) for isolators that rely on HEPA filtration for containment.
    
    
  • Perform additional tests as required by local and/or national jurisdictions to verify aseptic conditions.
    
    
• Make sure that workers performing maintenance are
  
  
  • familiar with applicable safety plans,
    
    
  • warned about hazards, and
    
    
  • trained in appropriate work techniques and PPE needed to minimize exposure.
    
    
• Remove all hazardous drugs and chemicals, and decontaminate the ventilated cabinet before beginning maintenance activities.
  
  
• Warn occupants in the affected areas immediately before the maintenance activity begins, and place warning signs on all equipment that may be affected.
  
  
• Strictly follow all applicable lockout/tagout procedures [29 CFR 1910.147].
  
  
• Decontaminate and bag equipment parts removed for replacement or repair before they are taken outside the facility.
  
  
• Seal used filtration media in plastic immediately upon removal, and tag it for disposal as chemotherapy waste; or dispose of it as otherwise directed by the environmental safety and health office or applicable regulation.

Routine Cleaning, Decontaminating, Housekeeping, and Waste Disposal

Cleaning and decontaminating

• Perform cleaning and decontamination work in areas that are sufficiently ventilated to prevent buildup of hazardous airborne drug concentrations. Develop protocols prohibiting the use of unventilated areas such as storage closets for drug storage or any tasks involving hazardous drugs.
  
  
• Clean work surfaces with an appropriate deactivation agent (if available) and cleaning agent before and after each activity and at the end of the work shift.
  
  
• Establish periodic cleaning routines for all work surfaces and equipment that may become contaminated, including administration carts and trays.
  
  
• At a minimum, wear safety glasses with side shields and protective gloves for cleaning and decontaminating work.
  
  
• Wear face shields if splashing is possible.
  
  
• Wear protective double gloves for decontaminating and cleaning work.
  
  
  • Select them by referring to the MSDS, glove selection guidelines, or information from the glove manufacturer.
    
    
  • Make sure the gloves are chemically resistant to the decomtamination or cleaning agent used.

Housekeeping

• Wear two pairs of protective gloves and a disposable gown if you must handle linens, feces, or urine from patients who have received hazardous drugs within the last 48 hours—or in some cases, within the last 7 days [Cass and Musgrave 1992].
  
  
• Dispose of the gown after each use or whenever it becomes contaminated.
  
  
• Wear face shields if splashing is possible.
  
  
• Remove the outer gloves and the gown by turning them inside out and placing them into the yellow chemotherapy waste container. Repeat the procedure for the inner gloves.
  
  
• Wash hands with soap and water after removing the gloves.

Waste disposal

• Be aware of the various types of waste generated by preparing and administering hazardous drugs: partially filled vials, undispensed products, unused IVs, needles and syringes, gloves, gowns, underpads, and contaminated materials from spill cleanups.
  
  
• Place trace wastes (those that contain less than 3% by weight of the original quantity of hazardous drugs)—such as needles, empty vials and syringes, gloves, gowns, and tubing—in yellow chemotherapy waste containers. Assuring that drug-contaminated waste is properly contained will protect workers from respiratory exposure to volatile or micro-aerosolized drugs [Connor et al. 2000; Kiffmeyer et al. 2002; Larson et al. 2003].
  
  
  • Place soft trace items (those that are contaminated with trace amounts of hazardous drugs) in yellow chemotherapy bags for disposal by incineration at a regulated medical waste facility.
    
    
  • Place empty vials and sharps such as needles and syringes in chemotherapy waste containers designed to protect workers from injuries and dispose of them by incineration at a regulated medical waste facility.
    
    
• Do not place hazardous drug-contaminated sharps in red sharps containers that are used for infectious wastes, since these are often autoclaved or microwaved [ASHP 1990; OSHA 1999; Smith 2002].
  
  
• Dispose of P-listed arsenic trioxide and its containers and any bulk amounts of U-listed drugs [40 CFR 261.33] in hazard ous waste containers at a RCRA-permitted incinerator. Nine hazardous drugs in Appendix A are listed as hazardous waste § by EPA.
  
  
• Consider disposing of other bulk hazardous drugs (that is, expired or unused vials, ampoules, syringes, bags, and bottles of hazardous drugs or solutions of any other items with more than trace contamination) in a manner similar to that required for RCRA-defined hazardous wastes as recommended by ASHP [1990] and OSHA [1999].

Spill Control

• Manage hazardous drug spills according to the established, written policies and procedures for each workplace.
  
  
• Be aware that the size of the spill might determine who is authorized to conduct the cleanup and decontamination and how the cleanup is managed.
  
  
• Assure that the written policies and procedures address the protective equipment required for various spill sizes, the possible spreading of material, restricted access to hazardous drug spills, and signs to be posted.
  
  
• Assure that cleanup of a large spill is handled by workers who are trained in handling hazardous materials [29 CFR 1910.120].
  
  
• Locate spill kits and other cleanup materials in the immediate area where exposures may occur.

§ Arsenic trioxide is a P-listed hazardous waste. Chlorambucil, cyclophosphamide, daunorubicin HCI, diethylstilbestrol, melphalan, mitomycin, streptozocin, and uracil mustard are U-listed hazardous wastes. See 40 CFR 261.33.

• As required by OSHA, follow a complete respiratory protection program, including fit-testing, if you wear respirators such as those contained in some spill kits [29 CFR 1910.134]. Use NIOSH-certified respirators [42 CFR 84]. Surgical masks do not provide adequate protection.
  
  
• Dispose of all spill cleanup materials in a hazardous chemical waste container, in accordance with EPA/RCRA regulations regarding hazardous waste—not in a chemotherapy waste or biohazard container.

Medical Surveillance

• In addition to preventing exposure to hazardous drugs and carefully monitoring the environment, make medical surveillance an important part of any safe handling program for hazardous drugs.
  
  
• If you handle hazardous drugs, participate in medical surveillance programs provided at your workplace.
  
  
• If you handle hazardous drugs but have no medical surveillance program at work, see your private health care provider for routine medical care. Be sure to inform him or her about your occupation and possible exposures to hazardous drugs.
  
  
• Refer to the OSHA Technical Manual: Controlling Occupational Exposure to Hazardous Drugs, Section VI Chapter 2 [OSHA 1999]. This document currently recommends that workers handling hazardous drugs be monitored in a medical surveillance program that includes the taking of a medical and exposure history, physical examination, and some laboratory tests.
  
  
• Refer to the guidelines of professional organizations such as the ASHP [1990] and the Oncology Nursing Society [Brown et al. 2001], which recommend medical surveillance as the recognized standard of occupational health practice for hazardous drug handlers. The American College of Occupational and Environmental Medicine (ACOEM) also recommends surveillance for these workers in their Reproductive Hazard Management Guidelines [ACOEM 1996].
  
  
• Use a worker’s past exposure history as a surrogate measure of potential exposure intensity.
  
  
• If you are an occupational health professional who is examining a drug-exposed worker, ask questions that focus on the worker’s symptoms relating to the organ systems that are known targets for the hazardous drugs.
  
  
  • For example, after an acute exposure such as a splash or other drug contact with skin or mucous membranes, focus the physical examination on the exposed areas and the clinical signs of rash or irritation to those areas.
    
    
  • Include a complete blood count with differential and a reticulocyte count in the baseline and periodic laboratory tests. These may be helpful as an indicator of bone marrow reserve.
    
    
• Monitor the urine of workers who handle hazardous drugs with a urine dipstick or a microscopic examination of the urine for blood [Brown et al. 2001]. Several antineoplastic agents are known to cause bladder damage and blood in the urine of treated patients.
  
  
• Conduct environmental sampling and/or biological monitoring when exposure is suspected or symptoms have been noted.
  

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