Laboratory Safety Manual

Reviewed May 2012

Appendix J
Cytotoxic/Antineoplastic Drugs

A list of cytotoxic/antineoplastic agents for which these procedures must be followed may be found in Appendix K of this manual.

More information can be found in the OSHA Technical Manual, Section IV - Chapter 2, "Controlling Occupational Exposure to Hazardous Drugs."

Drug Preparation

1. Personal Protective Equipment

• Surgical latex gloves should be used for the preparation of Cytotoxic/Antineoplastic Drugs (CDs) unless the manufacturer specifically stipulates that some other glove provides better protection. Powdered gloves should never be used. Because all gloves are to some extent permeable and their permeability increases with time, they should be changed regularly (hourly is preferable) or immediately if they are torn or punctured.
• A protective disposable gown made of lint-free low permeability fabric with a closed front, long sleeves, and elastic or knit-closed cuffs must be worn, with the cuffs tucked under the gloves. Gowns and gloves in use should not be worn outside the preparation area.
• A biological safety cabinet (BSC) is essential for preparation of CDs, but where one is not currently available, a respirator with a high-efficiency filter (preferably a powered air-purifying respirator [PAPR] used by personnel who have been trained to use respirators) will provide the best protection until the BSC is installed.

• Surgical masks do not protect against the breathing of aerosols. If a BSC is not in use, a plastic face shield or splash goggles complying with ANSI 28.7.1 criteria should also be worn and an eyewash fountain made available.

2. Preparation Area
   
   It is suggested that all CDs be prepared in one centralized area. If this is not practical, the number of areas used for preparation should be minimized. If possible, an isolated BSC, where only CDs are prepared, should be designated. Warning signs designating the area as a cytotoxic drug preparation area that should not be entered by unauthorized staff should be clearly posted. Spill procedures should also be posted. Eating, drinking, smoking, chewing gum, applying cosmetics, and storing food in or near the preparation area is forbidden.

   • A class II BSC must be used. The blower on the vertical airflow hood should be on at all times, 24 hours-a-day, 7 days-a-week. Venting to the outside is preferable where feasible, and is required with a Type B BSC. If the hood has an outside exhaust system, filtered exhaust to the outside should be an appropriate level and away from air intake units. BSCs must be certified by a qualified technician at least annually, after maintenance, or any time the cabinet is moved.
   • Technicians servicing these cabinets or changing High Efficiency Particulate Air (HEPA) filters should be warned of the nature of CDs and should use the same personal protective equipment as an employee dealing with a large spill.

   • All used gowns and gloves and disposable materials used in preparation should be disposed of as cytotoxic waste as directed by EHS.

3. Preparation Equipment
   
   Work with cytotoxics must be carried out in a BSC on a disposable, plastic-backed paper liner, which should be changed after preparation is completed for the day, or after a shift, whichever comes first. Syringes and IV sets with Luer-lock fittings should always be used, and syringes should always be large enough so that they need never be more than three-fourths full. A non-splash disposal collection vessel such as a plastic or metal tray lined with sterile gauze pads should be at hand to collect excess solution. All necessary items should be placed within the BSC before work is begun and all extraneous items should be kept out of the work area in order to avoid contamination.

   • The work areas should be provided with a closeable, puncture-resistant, shatter-proof container for disposal of contaminated sharp/breakable materials. Labeled sealable plastic or wire tie bags should be included at hand so that all boxes and other contaminated materials, including gloves, gowns, and paper liners, can be immediately placed in them and disposed of as cytotoxic waste as directed by the EHSO.

   • The cabinet should be cleaned daily with 70% alcohol and decontaminated weekly, whenever spills occur, or when the cabinet requires service or certification. Ordinary decontamination procedures, which include fumigation with a germicidal agent, are inappropriate in a BSC used for CDs because such procedures do not deactivate the drugs and may cause chemical reactions. Decontamination should consist of surface cleaning with high-pH agents followed by thorough rinsing. Removable work trays, if present, should be removed, and the back of the work tray and the sump below should be included in the cleaning.

4. Work Practices in Preparation
   
   Proper aseptic techniques are essential for worker protection. It should be noted, however, that BSC benches differ from horizontal flow units in several ways, thus requiring special precautions: manipulations should not be performed close to the work surface and un-sterilized items, including liners and hands, must be kept down-stream from the working area. Operators should be trained in these techniques.

   • Syringes and IV Bottles
     
     All syringes, IV bags and bottles containing CDs should be labeled with a distinctive warning label, such as "Chemotherapy--handle with gloves--dispose of properly."

   • Needles
     
     The use of large-bore needles, #18 or #20, will ensure that high-pressure syringing of the solutions is avoided. However, some experienced personnel believe that large-bore needles are more likely to drip. The needle should be chosen with these advantages or disadvantages in mind.

     1. Drug administration sets should be attached and primed within the hood, before the drug is added to the fluid, to obviate the need to prime the set in a less well-controlled environment, and to ensure that any fluid that escapes during priming contains no drug.

     2. All syringes and needles used in the course of preparation should be placed in the puncture-proof container for disposal without being crushed, clipped or capped.

   • Handling Vials
     
     Medical vials should not be vented unless a BSC is used as the work area or unless a hydrophobic-filter needles unit is available to eliminate pressure. Syringe and needle fitting should be of the Luer-lock variety.

     1. Diluent should be added slowly to the vial by alternately injecting small amounts, allowing displaced air to escape into the syringe. (All the diluent should not be injected at once; a large volume of displaced air will cause the syringe's plunger to back up and possibly spray the drug or cause leakage around the needles.) When all diluent has been added, a small amount of additional air may be withdrawn to create a negative pressure on the vial, but this should not be expelled into room air because it may contain drug residue. It should either be injected into a vacuum vial or remain in the syringe to be discarded.

     2. A sterile gauze should be wrapped around the needles and vial top when withdrawing solutions (Employees should take care to avoid needle sticks during this procedure.). This drug should be withdrawn from the vial while negative pressure is maintained.

   • Handling Ampules
     
     Any material remaining in the top of an ampule should be tapped down before it is opened. A sterile gauze pad should be wrapped around the ampule neck before breaking the top to protect against cuts and to catch aerosolized material.

     1. The ampule top should not be removed close to the employee's face. If diluent is to be added, it should be injected slowly down the inside wall of the ampule. The ampule should be tilted gently to ensure that all the powder is wet before agitating it to dissolve the contents.

     2. The needle should be held vertically with the needle upwards; the syringe should be tapped to remove air bubbles and the air bubbles expelled into sterile gauze, not into the air.

Drug Administration

1. Personal Protective Equipment

   • Personnel administering CDs should wear:

     1. a gown as described in "Drug Preparation" (see Personal Protective Equipment),
     2. disposable surgical latex gloves--double if appropriate, and

     3. a surgical mask also may be used.

   • It should be noted that this provides only minimal protection against CD aerosols and is no substitute for the proper procedures, which have been described.

2. Work Practices

   • Hands should be washed before putting on gloves. Gowns or gloves that become contaminated should be changed immediately.
   • Infusion sets and pumps which have Luer-lock fittings should be watched for signs of leakage during use. A plastic-backed absorbent pad should be placed under the tubing during administration to catch any leak. The line should be bled into a gauze inside a sealable plastic bag.
   • Priming should be carried out under a BSC. (If for some reason it must be carried out at the bedside) when priming IV sets or expelling air from syringes, a gauze in a plastic bag should be used as a receptacle. Syringes, IV bottles and bags, and pumps should be wiped clean of any drug contamination with an alcohol wipe. Needles and syringes should not be crushed or clipped, but should be placed in a puncture-resistant container to go into the CD disposal bag, along with all other contaminated materials. The bag should be disposed of as cytotoxic waste as directed by the EHSO.

   • Protective goggles should be wiped several times with an alcohol wipe and properly rinsed. Hands should be washed after glove removal. All gauze and alcohol wipes must be put in an appropriate disposal container.

Waste Disposal

Disposal of materials or animals containing or contaminated with cytotoxins or antineoplastic agents must be arranged through EHS.

1. Equipment
   
   Sealable plastic or wire tie bags of 4 mil thick polyethylene or 2 mil polypropylene, labeled with a cytotoxic hazard label and colored differently from other trash bags, should be used for the routine accumulation and collection of empty vials used containers, syringes, discarded gloves, gowns, goggles and any other disposable material. All CD-related wastes should be put into these bags, and nothing else.

   • Needles, syringes, and breakable items should be placed in a plastic vial or puncture-proof box before they are placed into the bag; needles should not be clipped or capped nor syringes crushed. The bag should be kept inside a covered waste container clearly labeled "cytotoxic waste only."

   • At least one such receptacle should be located in every area where the drugs are prepared or administered so that the waste need not be moved from one area to another. The bag should be sealed when it is filled and the carton should be taped.

2. Handling
   
   Housekeeping personnel must wear gowns and surgical latex gloves when handling the waste containers and should be instructed on the necessity of handling this waste with care and on procedures governing spills and leaks. Contact the EHSO for disposal of these wastes.

Spills

Spills and breakages should be cleaned up immediately by a properly protected person trained in the appropriate procedures. Refer to Section 1.3, "Biohazard Spills" for additional information.

Storage and Transport

1. Storage Areas
   
   Access to areas where CDs are stored should be limited to authorized personnel. Such areas should be posted with a large warning sign, a list of all drugs covered by CD policies, and a sign detailing spill procedures. Facilities used for storing CDs should not be used for other drugs and should be designed to prevent containers from falling to the floor. Warning labels should be applied to all CD containers, as well as the shelves and bins where these containers are permanently stored.

2. Receiving Damaged CD Packages
   
   Damaged cartons should be opened in an isolated area by an employee wearing the same protective equipment that is used during preparation (including a PAPR) without a hood.

   • Broken containers and contaminated packaging mats should be placed in a puncture-resistant receptacle and then in CD disposal bags, which should be closed and placed into appropriate receptacles.

   • The appropriate protective equipment and waste disposal materials should be kept in the area where shipments are received and employees should be trained in their use and the risks of exposure to CDs.

3. Transport
   
   Within the facility, drugs should be securely capped or sealed and packaged in impervious packing material for transport.

   • Personnel involved in transporting CDs should be cautioned and trained in the necessary procedures if a spill should occur, including sealing off the contaminated area and calling for appropriate assistance.

   • All drugs should be labeled with a warning label and clearly identified as cytotoxics. Transport methods that produce stress on contents (such as pneumatic tubes) should not be used to transport CDs.

Training and Information Dissemination

1. Training of Personnel
   
   All personnel involved in any aspect of the handling of CDs (shipment/receiving personnel, physicians, nurses, pharmacists, housekeepers, or employees involved in the transport or storage of drugs) must receive an orientation on CDs, including their known risks, relevant techniques and procedures for their handling, the proper use of protective equipment and materials, spill procedures, and medical policies. Prospective temporary and permanent employees who will be required to work with CDs should receive notice of this requirement.

2. Evaluation of Staff Performance
   
   Knowledge and competence of personnel should be evaluated after the first training session and at least annually thereafter. Evaluation may involve direct observation of an individual's performance on the job. Non-CD solutions may be used for evaluation of preparation techniques. Quinine, which will fluoresce under ultraviolet light, provides an easy mechanism for detection of clumsy technique.

Medical Surveillance

All employees with potential exposure to CDs through preparation, administration, housekeeping, waste disposal, transport or storage of CDs in addition to being fully informed of all potential dangers and the need to take adequate precautions, should have a baseline physical examination. Care should be taken to note any risk factors in the history. A complete blood count including differential may be taken to provide a baseline.

Annual medical monitoring should be performed under the recommendation of the University occupational health service.

A registry of all staff who routinely prepare or administer CDs should be permanently maintained, with the number recorded of each drug the employee has prepared or administered if this is feasible. Please provide EHS with a copy of this registry and current updates.

            Appendicies Bibliography