The cytotoxic drugs used to combat tumor cells can also harm normal cells and their DNA, and these drugs represent a significant occupational exposure risk for hospital pharmacy and infusion center personnel.1 Occupational exposures can cause acute symptoms such as nausea and skin and eye irritation; and theyhave been tied to significantly increased rates of DNA damage, infertility, miscarriage, premature birth, and congenital problems among prenatally-exposed children, including low birth weight, learning disabilities, and limb abnormalities.1-3 The teratogenic risks are well-established for interferon alpha-2b, leflunomide, methotrexate, thalidomide, and tositumomab, for example.1 Many anti-cancer drugs are also known or probable carcinogens and are believed to be at least partly responsible for increased cancer rates among health care workers (Table 1).1,4,5
Even in their diluted forms, completely safe levels of occupational exposure to these drugs have not been established, leading US occupational health agencies to champion an “as low as reasonably achievable” (ALARA) approach to the handling and preparation of these drugs by health care personnel.6,7 Simply put, the goal should be to avoid occupational exposures altogether.8 In 1986, as a step toward that goal, the US Occupational Safety and Health Administration (OSHA) released guidelines and recommendations intended to prevent occupational exposures. (These guidelines were updated in 1999 and are summarized in Table 2.)
CONTAMINATION: UNDERRECOGNIZED AND EXTENSIVE
Exposures may result from direct skin contact or inhalation of vapors, dusts, or aerosols during drug preparation or administration, or from indirect exposure to contaminated surfaces, such as drug vials.1,7,9 Indirect exposures are a frequently underappreciated route of occupational exposure to these drugs. For example, in 1998, officials at M. D. Anderson Cancer Center in Houston, Texas, were shocked to discover the extent of environmental contamination with anticancer agents at their facility.
“We had someone come in and do wipe samples where we were making IVs,” recalled staff pharmacy manager Susan Spivey, PharmD, DDS, RPh. “They took samples in the pharmacy, at the hoods, and then in the halls and the nursing units.” (Dr Spivey served as an advisor to the Swedish firm Carmel Pharma until 2009, she said. As noted below, Carmel manufactures PhaSeal, one of the closed-system drug transfer devices reviewed in this article.)
Because staff observed the 1986 OSHA safe-handling guidelines, Dr Spivey and her colleagues had been overconfident, she said in retrospect. “We thought we’d come out fine,” Dr Spivey said. “We were wrong. We had contamination all over the IV room, outside where pharmacists had been and up and down the hallway to the nursing unit. It was a surprise; I had thought if we had any contamination, it would be limited to the pharmacy.”
Dr Spivey’s primary concern was for the potential harm to infusion staff, but given the extent of the contamination, she also worried about other visitors to the center. “[My concern] was global, all the way down to not exposing patients and family members—or anybody else who was around the IV pharmacy,” Dr Spivey said. “But the main concern was that the more you encounter it, the greater the chances of contamination or repeated contamination you have, the greater your chances are of harm. One-time exposures from walking through the area are not going to [involve the same risk]. But these are carcinogens, and some of the risks start with pregnancy—having miscarriages or low-weight babies, or babies with developmental problems and inappropriate limb growth. Exposures can years later lead to acute leukemias.”
THE EVOLUTION OF GUIDELINES
OSHA’s 1986 guidelines were updated in 1999 and remain a core strategy for avoiding environmental contaminations and occupational exposures involving antineoplastic agents. The guidelines recommend periodic testing of ventilation systems and protective equipment, the use of personal protective equipment and hand hygiene practices, and the availability to all staff, contractors, and employees of a written Hazardous Drug Safety and Health Plan describing exposure-prevention practices.7 The OSHA guidelines recommend that designated hazardous drug handling areas be established, that dedicated biological safety cabinets (BSCs) be used to contain hazardous agents and reduce exposure risk during dose preparation, and that personal protective equipment be used consistently during dose preparation, including gowns, gloves, respiratory protection, and eye, nose, and mouth protection.
M. D. Anderson was not the only facility with concerns about contamination and exposure despite observance of OSHA guidelines. In 2004, the National Institute for Occupational Safety and Health (NIOSH) issued an alert calling for additional safe-handling guidelines, including the use of closed-system drug transfer devices (CSTDs), defined as self-contained systems that prevent the escape of hazardous drugs or drug vapors (see Table 2).8
PROTOTYPE TO PRACTICE
By 2004, M. D. Anderson was well ahead of most US cancer centers, already using CSTDs, in part because it had helped develop the device’s prototypes through collaborations with Carmel Pharma, Dr Spivey said. CSTDs were a newly emerging technology when M. D. Anderson started looking into better isolation controls in 1999, Dr Spivey said, and Carmel’s PhaSeal was the only CSTD on the market.
“It was being used in Sweden on a very, very small level,” Dr Spivey said. “Oncology nurses were using it on countertops to mix chemo agents there. They brought the prototype to Houston, and we used it in the first study and found a lot of problems. They took it back to Sweden and made the fixes, and we’ve used it ever since.” Among the problems M. D. Anderson identified in the early PhaSeal system, Dr Spivey told Oncology Nurse Advisor, were loose fittings that caused leaks and malfunctioning spikes that didn’t always work with IV bags, leading to leaks.