Protecting Health Care Workers: Handling Hazardous Drugs

Proposed regulations call for the use of closed-system transfer devices by health care workers handling hazardous drugs.

Medications that can save the lives of patients with cancer can also pose a handling risk to health care professionals. After a 23-year career preparing medication in a hospital pharmacy, pharmacist Sue Crump developed a particularly deadly form of cancer: pancreatic cancer. Although she outlived her prognosis several times, sadly, Sue Crump died of pancreatic cancer in 2009. She was 55 years of age. It was her wish to educate young pharmacists about the risk of chemotherapy handling and the importance of safe chemotherapy handling procedures.¹

In an interview with PBS Newshour that aired in 2010, Sue Crump stated, “By the time I was diagnosed, I had already lost quite a bit of weight.”

Not only had Sue developed cancer, but many of her former coworkers had also developed various types of cancer. She continued, “One of my friends after another was coming down with either some very rare, exotic, bizarre disease; brain tumors; sarcoidosis; arrhythmias; or cancer.”²

Sue Crump is not alone. Pharmacist Bruce Harrison, veterinarian Brett Cordes, and nurse Sally Giles all eventually developed cancer or precancerous conditions in their fourth or fifth decade of life after being exposed to the occupational risk of hazardous drug handling. Sadly, Bruce Harrison, who had a key role in developing hazardous drug handling guidelines, died at the age of 59. Sally Giles died of bile duct cancer in 1992. Brett Cordes has since recovered from cancer, but has left private practice to advocate for improved compounding safety standards.^1,3-5

The issue of hazardous drug handling is not limited to cancer risks. Reproductive toxicity is also an important issue, as many hazardous drugs may harm nursing infants or a developing fetus. One breastfeeding health care worker, perfusionist Anne Oulton of Brigham and Women’s Hospital in Boston, sued her employer after she was assigned to administer chemotherapeutic medications to a patient, despite the fact that Oulton was breastfeeding her 3-month-old daughter at the time. Over several weeks in 2010, Oulton administered the medication a total of 5 times, while a male colleague was excused from the task. Oulton sued for gender discrimination and a hostile work environment.⁶

These and other cases have led to legislative discussions in Washington about the importance of the safe handling of hazardous drugs. Some states, notably Washington, Maryland, and North Carolina, have already adopted more stringent standards regarding the storage, handling, and transport of hazardous medications. In addition, if approved, a set of proposed draft regulations known as USP <800> will be a federally enforceable mandate, unlike previous guidelines, which were recommendations.⁷

These proposed regulations are not simply the result of anecdotal reports and activism. Abundant published research links chemotherapy handling and preparation with cancers and reproductive hazards. The Centers for Disease Control and Prevention keeps a running catalog of guidelines, surveys, and review articles documenting the occupational safety hazards associated with chemotherapeutic medications.⁸ The list, which is maintained by National Institute for Occupational Safety and Health research biologist Thomas Connor, reflects the unique hazards of the pharmacy profession. According to Connor, regarding pharmacists, “There is no other occupation population that handles so many known human carcinogens.”¹

Seminal research regarding the risks of health care worker hazardous drug exposure includes:

• 2010 study results (by McDiarmid et al) published in the Journal of Occupational and Environmental Medicine show significantly higher rates of chromosome 5 and 7 abnormalities among health care workers handling antineoplastic medications. In the study, blood samples were collected from 109 health care workers and the frequency of hazardous drug handling was compared with the presence of chromosomal abnormalities. Researchers compared a higher-exposure group with a lower-exposure group. In the higher-exposure group, study results indicated significantly higher rates of structural chromosomal abnormalities (0.18/person vs 0.02/person; P = .04), a 24% greater risk of chromosome 5 abnormalities (P = .01), and a 20% greater risk of chromosome 5 or 7 abnormalities, which was also statistically significant (P = .01).⁹
• A 1999 study (by Valanis et al) published in the Journal of Occupational and Environmental Medicine compared pregnancy outcomes in 2976 nurses, pharmacists, and pharmacy technicians with outcomes in 4118 pregnancies among women who were not health care workers. The risk of spontaneous abortion or stillbirth was 40% higher in women handling hazardous drugs during pregnancy, which was statistically significant based on a confidence interval that did not cross unity (OR 1.4; 95% CI, 1.2-1.9).¹⁰

Even more concerning, the risks of reproductive hazard and genotoxicity are still present after the introduction of numerous safety standards. Previously, few safety systems were in place: in the early 1980s, pharmacists would prepare medications like cyclophosphamide, doxorubicin, fluorouracil, and methotrexate without the benefit of medication containment hoods. Medication droplets and vapors would spray out of vials due to pressure differences between the inside of the vial and outside environment. At times, medications spilled on preparation areas, resulting in hazardous drug exposure as the spills were cleaned.¹

Over the years, with regulatory change and voluntary guideline adherence, chemotherapy handling rules changed. However, not all risks have been addressed. Research shows that even with modern chemotherapeutic medication preparation protocols, health care workers are still exposed and surfaces throughout hospitals and medication preparation areas are contaminated. This translates to real harm and exposure risk.¹

New regulations, such as the proposed USP <800>, will address the risks of chemotherapeutic drug handling. Among the key safety protocols is the use of closed-system transfer devices (CSTDs). Under proposed regulations, use of CSTDs will be required among nurses who are administering hazardous drugs to patients and recommended for pharmacists compounding medications.⁷

With requirements changing, many hospitals will have to choose among a variety of CSTD systems. Currently, 5 such systems are available on the US market. These are the BD PhaSeal system by Becton Dickinson, SmartSite/ Texium by CareFusion (now a Becton Dickinson company), On-Guard/ Tevadaptor by B. Braun, ChemoClave/ Spiros/ChemoLock by ICU Medical, and Equashield/Equashield II.⁷

It is important to choose a system that has robust evidence of efficacy in protecting health care workers. Published research supports the efficacy of these systems. For instance:

• More than 25 published studies support the performance and efficacy of the BD PhaSeal System in protecting health care workers from hazardous drugs (see www .bd.com/pharmacy/phaseal/evidence/ studies.asp).
• In a 2011 study published in the Journal of Oncology Pharmacy Practice, Sessink et al reported levels of surface contamination of antineoplastic drugs in 22 US hospitals before and several months after adoption of the BD PhaSeal CSTD system. However, the levels of surface contamination found after for all 3 antineoplastic drugs sampled were significantly lower: cyclophosphamide (95% reduction; P <.0001), ifosfamide (90% reduction; P <.001), and 5-fluorouracil (65% reduction; P <.01).¹¹
• In a 2003 study published in the American Journal of Health Systems Pharmacy, Wick and colleagues determined that the BD PhaSeal system led to real-world reductions in personnel exposure. Before and 6 months after implementation of BD PhaSeal CSTD in a hospital pharmacy, all personnel were evaluated using 24-hour urine samples. Of 8 employees, 6 showed evidence of exposure to cyclophosphamide and 2 showed evidence of ifosfamide exposure prior to use of the BD PhaSeal System. After implementation, none of the 8 employees had evidence of cyclophosphamide or ifosfamide in their urine samples.¹²
• In a 2013 study published in the Journal of Oncology Pharmacy Practice, Clark and colleagues reported the efficacy of the EquaShield CSTD on reducing surface contamination at a single cancer center before and after the system’s adoption. Researchers used a kit to collect samples from 5 areas of the pharmacy, 5 areas of the infusion suite, and 2 areas in offices. Whereas approximately half of the samples showed contamination before, no contamination with cyclophosphamide or 5-fluorouracil was identified in the final sample collection (see http://equashield.com/ uploads/article.pdf).¹³

Mike Van Fleet, senior business director of medication and procedural solutions at Becton Dickinson, noted, “We are excited to bring together BD’s leading PhaSeal technology with CareFusion’s Chemo Safety System and leadership in IV sets to ensure more health care workers are protected across the entire continuum of hazardous drug preparation, delivery, and disposal. Products and solutions that enable the safe preparation, delivery, and disposal of hazardous drugs are a strategic part of our combined company’s portfolio. With our customers’ best interests in mind, we plan to continue to supply all of the hazardous drug safety products in our combined portfolio, and, of course, we will continue to invest and upgrade our offerings to provide customers with the most complete selection of solutions.”

Regarding Equashield’s commitment to quality, cofounder Marino Kriheli stated, “Our company has always listened and responded to our customer needs by providing them with solutions that protect health care workers from hazardous drug exposure. We spent a great deal of time during the product development phase of Equashield to ensure that the original design was based on a broad overview of the safety and use needs of the hospital. We are constantly looking for ways to improve our system by learning the needs of the field and adding components that allow special procedures.”

Kriheli continued, “We are constantly looking for ways to improve our system by learning the needs of the field and adding components that allow special procedures.”

The commitment of these CSTD manufacturers to product quality reflects a greater industrywide emphasis on safe handling of hazardous drugs and reflects the changes brought on by advocacy from Sue Crump and other health care workers. Before Sue died, she spoke about the importance of safe chemotherapy handling in an interview with The Seattle Times. “Safety needs to be revisited,” she said. “People don’t take this seriously enough.”¹

With new regulations pending approval for safer handling of hazardous drugs and requirements for the use of CSTD systems in hospitals, Sue’s wish is finally being taken seriously. Regulations in proposed USP <800> will require use of CSTDs during administration of chemotherapy to patients. With this proposed regulation, health systems will have to make a choice about the right system for their needs.⁷

It is important to choose a system that has strong evidence of protective performance to safeguard health care workers who care for seriously ill patients every day. Helping patients while protecting these health care workers and following regulations is an important priority for health systems across the United States.

Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.

References

• Smith C. Lifesaving drugs may be killing health workers. The Seattle Times. July 10, 2010. www.seattletimes.com/seattle-news/lifesaving-drugs-may-be-killing-health-workers. Accessed April 2015.
• Examining chemo drugs’ potential threats to health care workers. PBS Newshour website. August 5, 2010. www.pbs.org/newshour/bb/health-july-dec10-chemo_08-05. Accessed May 2015.
• Rodriguez P. Agent of change. Veterinary Practice News. October 18, 2010. www.veterinarypracticenews.com/October-2010/Agent-Of-Change. Accessed May 2015.
• Morris J. What if the cure is also a cause? The Washington Post. February 15, 2005. www.pr.com/upload/presskit_1527_1119288849.pdf. Accessed May 2015.
• Exposure may have killed author of safety guidelines. The Seattle Times. July 10, 2010. www.seattletimes.com/seattle-news/exposure-may-have-killed-author-of-safety-guidelines. Accessed May 2015.
• Murphy S. Breastfeeding worker sues hospital over chemo case. The Boston Globe. April 10, 2015. www.bostonglobe.com/metro/2015/04/09/breastfeeding-worker-sues-hospital-over-chemo-case/oOprbZUVXUYrEc7KOrBFzI/story.html. Accessed April 2015.
• Page MR. USP <800>: new regulations to protect health care workers from hazardous drugs. Specialty Pharm Times. 2015:6(2):30-34. www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2015/April-2015/USP-800-New-Regulations-to-Protect-Health-Care-Workers-from-Hazardous-Drugs. Accessed April 2015.
• Centers for Disease Control and Prevention. Occupational exposure to antineoplastic agents and other hazardous drugs. www.cdc.gov/niosh/topics/antineoplastic/pubs.html#sthash.C2VMKDi2.dpuf. Accessed April 2015.
• McDiarmid MA, Oliver MS, Roth TS, Rogers B, Escalante C. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010;52(10):1028-1034.
• Valanis B, Vollmer WM, Steele P. Occupational exposure to antineoplastic agents: self-reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med. 1999;41(8):632-638.
• Sessink PJ, Connor TH, Jorgenson JA, Tyler TG. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract. 2011;17(1):39-48.
• Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm. 2003;60(22):2314-2120.
• Clark BA, Sessink PJ. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract. 2013;19(2):99-104.