HOUSTON – PHARMACISTS AND nur ses using Class II biological safety cabinets (BSCs) to prepare chemotherapy drugs are potentially at risk for cancer and adverse reproductive effects because of contamination problems related to the BSCs. According to a report published in the July issue of American Journal of Health-System Pharmacy, exposure to antineoplastic agents, chemotherapy drugs that are also called cytotoxics, is “commonplace” despite precautions.
Authors of the report write that “reliance on BSCs to provide total protection from exposure may be misguided and may provide a false sense of security.” Even pharmacy workers not directly involved in the preparation, administration and disposal of antineoplastic agents are at risk of exposure, the authors conclude.
Of the approximately 40 drugs used to treat cancer patients, 20 are known as or suspected to be human carcinogens, and others cause acute toxic affects.
“There's no other occupation where people are exposed to such a large number of human car cinogens,” says the report's principal inves tigator, Dr. Thomas Connor, a genetic toxicologist and associate professor of En vi ron mental Sciences and Occupational Health at the University of Texas (UT) School of Public Health (Houston).
Several European studies have documented the BSC contamination problem, but the current report is the first comprehensive study in North America. The research found antineoplastic surface contamination in six cancer treatment centers in the U.S. and Canada. Each center used Class II BSCs to prepare an average of 30,000 cytotoxic doses annually.
Using a wipe sampling method, research ers found substantial levels of contamination – in all six facilities – from three antineoplastics: ifosfamide, fluorouracil and cyclo phosphamide. The latter is a known human carcinogen. The contamination was found in preparation areas on the BSC work surface, underside of the grille, airfoil and the adjacent floor; in the administration areas on the floor around the patients' beds; and in other work areas on the floor. Surfaces immediately adjacent to the BSCs were typically found contaminated with levels of the antineoplastic agents as high as or higher than levels in the BSCs themselves.
Preparation of the chemotherapy drugs for administering to patients is a labor-intensive task that requires hands-on manipulation by the healthcare worker. The worker must create the product from a liquid or powder contained in a vial sent from the manufacturer, then withdraw the drug into a syringe – procedures performed inside the BSC. At the patient bedside, the drug is injected into an intravenous unit.
These procedures are the likely source of contamination, Connor says. They produce spills inside the BSC, which then leak onto the floor and get tracked around the pharmacy work areas. They can also produce aerosols and vapors much smaller than the 0.3 micron pore size of the BSC's HEPA filter, thus exposing the workers by inhalation when the vapors are released into the environment. In addition, most of the BSCs used in the preparation of chemotherapy drugs vent back into the pharmacy through a second HEPA filter, Connor says. Only a few are partially or completely exhausted to outside air.
The research study was funded by Carmel Pharma (Goteborg, Sweden), which has developed a closed, disposable syringe device that would contain spills from manipulation of the cytotoxics and replace engineering controls, such as the Class II BSC. Phase one of the research sought to determine the extent of the contamination. The second phase, which is currently underway, will test the technology's ability to decrease the contamination.
Ironically, it was a contamination problem with horizontal laminar airflow hoods that led to the use of Class II BSCs as a means of containing the antineoplastics during preparation and reducing worker exposure. A 1982 study by the UT School of Public Health and one of the current report authors, Dr. Roger Anderson, head of the pharmacy division at the UT M.D. Anderson Cancer Center (Houston), showed evidence of antineoplastic agents in the urine of healthcare workers using the hoods. After the workers switched to Class II BSCs, the antineoplastic levels in the urine dropped to a nondetectable level, which implied that Class II BSCs were effectively containing the agents.
The urine detection method used at that time detected levels in micrograms, but analytical techniques sensitive to nanograms have since been developed. Using these new techniques, European researchers have demonstrated the presence of antineoplastic agents in urine samples collected from pharmacists, technicians and nurses using Class II BSCs and gloves as the minimum level of protection. Cyclophosphamide was also found in the urine of workers not directly involved in drug preparation. “We assumed that because we could not find levels with the previous method that there was not a problem,” Connor says.
Since the current report was published, its authors have received numerous inquiries from healthcare workers wanting information on ways to minimize the contamination problem. The researchers stress strict adherence to published guidelines on handling the antineoplastics, use of protective equipment and proper cleaning techniques.
“The first thing to do is look at training and individual cleanliness. A lot of it is technique, and if it requires a few more minutes and extra cleaning at the end of the day, that's what can be done within our limited budgets,” says Luci Power, one of the report's authors who is a practicing hospital pharmacist and biosafety consultant with Power Enterprises (San Francisco, CA). Connor agrees. “People assume that a BSC is protecting them 100 percent, and sometimes they are not as cautious as they should be,” he says.
In addition, pharmacies with BSCs vented back into the indoor environment should consider either a partial or total exhaust, he adds. “Venting can be very costly and could require the purchase of a different type of BSC and installation of ducts, which also require heating and/or air conditioning enhancements. From a safety standpoint, 100 percent exhaust would be the way to go. It gets rid of more material that way, but it's not always a practical approach.”
Connor is hesitant to recommend use of a Class III BSC or a barrier isolator because no studies have been performed proving their ability to contain the agents. But to Power, barrier isolators are more cost-effective than Class III BSCs and may provide a solution to the problem, especially when installing new equipment.
The risk for cancer from exposure to these cytotoxics is documented in patients, but not in healthcare workers. An epidemiological study of cancer end points in pharmacists and nurses is the logical next step, but Connor says he is not aware of such a study in the works. While the data is not available to prove a risk for cancer, “wisdom tells us that we should not be exposing workers to these drugs,” Connor says.
 Conner: BCSs don’t provide 100 percent protection. |
Without funding from Carmel Pharma, the current study would not have been performed, Power says. With no highly publicized deaths or miscarriages resulting from exposure, and with no court cases to attract attention, there is no industry or government support to fund research in this area.
“Although we are seeing contamination, and although the impetus for this study came from Europe, we are not seeing any epidemic or endemic results with the containment that we are currently using. The other side to that coin is that we haven't looked for anything,” Powers says.
Other industries' use of known carcinogens is closely regulated, but the healthcare industry has been mostly exempt from regulatory control. Only one U.S. federal regulation governs worker exposure to cytotoxics: the 1994 Hazardous Communications Final Rule (29 CFR Part 910). That rule requires employers to define and inform workers of a hazard, use proper engineering controls and train workers on handling toxic substances. It doesn't specify training or protective mechanisms, but refers to current guidelines on the topic.
The many guidelines available – from the European Union, Occupational Safety and Health Administration and other agencies and organizations, including the American Society of Health-System Pharmacists (ASHP) – recommend policies and procedures related to facilities; use of equipment, such as the Class II BSC; and personnel practices. ASHP has its Technical Assistance Bulletin, “Handling Cytotoxic and Hazardous Drugs,” posted at www.ashp.org.
Information on the current report and other reports linking Class II BSCs and antineoplastics contamination is available at www.uth.tmc.edu/schools/sph/an_agents.