Strategies for Protecting Pharmacists from Chemotherapeutic Medication Contamination During Compounding

The use of closed-system drug transfer devices can help protect pharmacists from potential harm from exposure to hazardous drugs, such as chemotherapeutic medications.

Many chemotherapeutic drugs, even in minute amounts, are known for their ability to interfere with cell growth and division. Evidence suggests that pharmacists who handle these drugs may be exposed to enough chemotherapeutic medication to induce harmful adverse events.^1,2

“Chemotherapy drugs kill cancerous cells, but health care workers who deal with these drugs, like in pharmacies, are exposed to them on a daily basis over many years,” said EquaShield cofounder Marino Kriheli, whose company designed a shielded closed-system drug transfer device (CSTD) to protect health care workers from exposure to chemotherapy drugs. “Small quantities of the drugs can cause health problems for those people, such as cancer, infertility, and birth defects, which are typical outcomes from being exposed to those drugs during daily life.”

Particularly at risk are health care workers who may wish to have children, as exposure to these medications can induce chromosomal abnormalities and can interfere with fetal development.

In a 2010 study, McDiarmid and colleagues identified a higher rate of chromosome 5 and 7 abnormalities among health care professionals (HCPs) handling anticancer drugs. Of 109 HCPs sampled, those who were involved in chemotherapeutic drug compounding had a significantly higher rate of structural chromosomal abnormalities versus HCPs with no exposure to the drugs. The risk of chromosome 5 and 7 abnormalities was increased with each instance of drug handling. Investigators estimated that, in an HCP who has handed chemotherapeutic drugs at least 100 times, the risk of chromosome 5 and 7 abnormalities increased by 20% versus unexposed control individuals (P = .01).¹

These chromosomal abnormalities may lead to negative health effects. For instance, in a 1999 study published in the American Journal of Health-System Pharmacy by Valanis and colleagues, investigators surveyed pregnancy outcomes among 2976 pregnancies of pharmacy and nursing staff versus 4118 control pregnancies. Results of the trial revealed a 40% higher risk of spontaneous abortion and stillbirth among women who handled chemotherapeutic medication during pregnancy (odds ratio [OR], 1.4; 95% CI, 1.2-1.9).²

“The drugs are sticky and they don’t disappear like water that dries out, so small quantities here and there remain on surfaces when people touch them,” Kriheli said. “Either by inhalation or contact with the skin, these drugs find their way into the body of innocent people. Many studies have shown these drugs were found in the urine of health care workers.”

Fortunately, compounding processes generally involve careful controls, as enumerated in the USP <797> guidelines for compounding of sterile preparations, as well as draft USP <800> guidelines for hazardous drug handling in health care settings. One important compounding control is the CSTD, which does not allow hazardous drugs being compounded to leak or to be vented to the outside environment. Due to the risk of exposure to certain chemotherapeutic drugs, CSTDs are preferred per USP compounding guidelines.³

“All regulatory organizations recommend and partially mandate the use of so-called CSTDs, which are a missing part of the chain in fighting against exposure to hazardous drugs,” Kriheli noted.

Several CSTD devices are available on the US market, including the EquaShield System and Becton Dickinson’s PhaSeal System. Evidence supports the efficacy of each of these systems in reducing chemotherapeutic drug contamination in actual pharmacy practice settings.^4,5

EquaShield

Investigators Clark and Sessink evaluated the use of EquaShield versus traditional technique in an ambulatory cancer chemotherapy infusion center. Before the infusion center began using the EquaShield CSTD, surfaces were assessed for baseline levels of drug contamination with 5-fluorouracil or cyclophosphamide. After all surfaces had been thoroughly cleaned, pharmacy staff used EquaShield’s system exclusively starting in June 2010. At 2 time points (August 2010 and August 2011), pharmacy surfaces (including office and work area surface) were reassessed for surface contamination.⁴

Of 12 locations sampled at baseline, 7 areas were contaminated—including areas in the pharmacy, the infusion suite, and offices. After cleaning and utilizing EquaShield’s system, no contamination was present in any location tested at both time points. These results show that EquaShield’s system protects pharmacy staff and other health care professionals from exposure to potentially dangerous chemotherapeutic drugs in a real-world setting.⁴

“There are good systems that provide full protection against all routes of exposure and some systems that only have partial protection,” Kriheli said. “They use filters, for example, to vent air outside the system to equalize pressure in the system, but there is no filter in the world to stop the vapors of these drugs, so they enter the environment unhindered. These are the bad systems, the non-performing systems.”

PhaSeal CSTD

Investigators tested the BD PhaSeal CSTD in a study conducted across 22 hospital pharmacies in the United States. Prior to the utilization of a CSTD system in these pharmacies, investigators measured levels of antineoplastic medications (ie, cyclophosphamide, ifosfamide, and 5-fluorouracil) in locations throughout each pharmacy.⁵

From June 2000 to May 2005, investigators assessed levels of surface chemotherapeutic drug contamination at each hospital pharmacy using a system called the Cyto Wipe Kit before and several months after implementation of the CSTD PhaSeal system. In the final analysis, median contamination levels of cyclophosphamide were reduced by 95%, median contamination levels of ifosfamide were reduced by 90%, and median contamination levels of 5-fluorouracil were reduced by 65%.⁵

In a follow-up analysis of 30 US hospital pharmacies in 2013, Sessink and colleagues expanded data collection to 2004 to 2010, and found significant (P <.0001) reductions in cyclophosphamide contamination 6 or more months after implementation of the BD PhaSeal System.⁶

The lack of environmental contamination was also found to translate to less human exposure. In a single-center study by Wick and colleagues, prior to utilizing the PhaSeal CSTD, the urine samples from 6 out of 8 employees contained cyclophosphamide and 2 samples contained ifosfamide. After 6 months using the PhaSeal CSTD, no instances of urine contamination were detected.⁷

“The BD PhaSeal System exemplifies our goal of enabling health care facilities to reduce workplace hazards and adhere to compliance standards while providing quality patient care,” said Richard Byrd, vice president of medication preparation solutions at BD Medical.

Byrd also emphasized the considerable evidence base supporting the efficacy of the BD PhaSeal system.

“The BD PhaSeal System has an extensive amount of research and evidence that validates the efficacy of the system in helping reduce health care exposure to hazardous drugs and human uptake, and proving its ability to maintain a closed, leakproof, and airtight system,” he noted.

With data including 2 large, multicenter US analyses,^5,6 and real-word reductions in employee exposure, the BD PhaSeal system is supported by a high level of evidence. Although reducing environmental contamination is a proximate measure of employee exposure to chemotherapeutic drug contamination, Wick and colleagues have shown that the BD PhaSeal CSTD system actually translates to less exposure to chemotherapeutic agents.⁷

“In addition to providing health care worker safety, further studies have demonstrated the system’s ability to maintain drug sterility for up to 168 hours within an ISO Class V environment,” Byrd said. “This capability may also create more efficiency and cost-saving opportunities.”

The BD PhaSeal System, and many other innovative pharmacy solutions from BD, “continue to demonstrate BD’s comprehensive approach to protecting health care workers from occupational hazards, standardizing practice, streamlining workflow and increasing efficiency from medication preparation and administration to disposal,” according to Byrd.

Conclusion

Considering the substantial evidence indicating chromosomal abnormalities and potential harms to pregnant women, taking precautions to protect HCPs from the potential harms of anticancer drugs is an important priority. Compounding guidance enumerated in USP <797> and draft USP <800> guidelines advocate use of CSTD systems in compounding of sterile preparations. Abundant evidence indicates that this technology helps contain chemotherapeutic drugs during compounding, reducing the likelihood of harm to HCPs. SPT

References

• 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.
• United States Pharmacopeial Convention. General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. www.usp.org. Accessed October 2014.
• 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.
• 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.
• Sessink PJ, Trahan J, Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device. Hosp Pharm. 2013;48(3):204-212.
• 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):2314-2320.