TON - Supplements - Oncology Pharmacy

In 1979, Falck and colleagues described the presence of chemotherapy in the urine of nurses caring for patients who had received chemotherapy.1 The discovery that merely handling chemotherapy drugs can lead to absorption of the chemotherapy drugs has been key in the re-evaluation of safety in healthcare environments. In 2004, the National Institute for Occupational Safety and Health (NIOSH) alert noted that skin rashes, infertility, miscarriage, birth defects, and leukemia or other cancers may be associated with working with or near hazardous drugs.2

Over the years, the Oncology Nursing Society (ONS), United States Pharmacopeial Convention (USP), American Society of Health-System Pharmacists (ASHP), and American Society of Clinical Oncology (ASCO) have developed guidelines that identify healthcare workers who are at risk for exposure to hazardous drugs, and methods for reducing those risks.3

What Is a Hazardous Drug?

In the NIOSH Working Group on Hazardous Drugs’ revision of the ASHP’s definition of hazardous drugs from 1990, hazardous drugs are identified as having ≥1 of the following characteristics: carcinogenicity, teratogenicity (or other developmental toxicity), reproductive toxicity, organ toxicity at low doses, or genotoxicity. If a drug has a structure and toxicity profile that mimics existing drugs that are determined to be hazardous according to the aforementioned criteria, then the drug is considered hazardous.4

Per the 2004 NIOSH alert, hazardous drugs are also defined as agents that have the potential to cause cancer, developmental or reproductive toxicity, or organ harm in studies of people or animals exposed to them.2 NIOSH also reports that even exposure to small concentrations of certain drugs may be hazardous for those who handle them.2 According to the Centers for Disease Control and Prevention, adverse events are associated with acute symptoms (eg, nasal sores, hair loss), adverse reproductive outcomes (eg, infertility, miscarriages), genetic changes, and an increased occurrence of cancer.2 According to the 2014 list of hazardous drugs in healthcare settings by NIOSH, 97 antineoplastic agents meet ≥1of the NIOSH hazardous drug criteria.4 Although the list does not include immunotherapy agents, it does include the conjugated monoclonal antibodies brentuximab vedotin and ado-trastuzumab emtansine, as well as the Bacillus Calmette-Guérin vaccine. In addition, the list includes 87 nonantineoplastic drugs that meet the criteria of a hazardous drug, or have known adverse reproductive effects.

Who Is at Risk for Hazardous Drug Exposure?

The risk for exposure to hazardous drugs in healthcare professionals begins with the arrival of dangerous agents to their institution, and ends with proper disposal. Those who are at highest risk for exposure extensively handle hazardous drugs, and are primarily those who compound and/or administer chemotherapy agents (eg, pharmacists, pharmacy technicians, and nurses).2

However, other members of the staff may also come into contact with hazardous drugs, or areas contaminated with hazardous drugs. For example, people who receive and inspect packages, transport cartons to pharmacies, or bring prepared medications to the clinical area are also at risk for exposure. Because of the serious implications of hazardous material exposure, it is important for all healthcare professionals to be aware of the risks involved in handling hazardous drugs, and to practice safe-handling techniques, regardless of whether their exposure risk is minimal. Roles and activities, together with their potential route of exposure to hazardous drugs, are outlined in Table 1.5

Table

Hazardous drug exposure may also occur outside of traditional healthcare settings. Patients are sent home with ambulatory pumps infusing chemotherapy for days or weeks. These patients are not necessarily homebound, and care must be taken to ensure that hazardous agents do not leave their home and spread to public areas. Education about hazardous materials is critical for everyone, but providing safe-handling education and spill management tools is especially important for patients and families handling hazardous drugs within their homes.

Policies and Guidelines

In 2007, the International Society of Oncology Pharmacy Practitioners published standards of practice for the safe handling of cytotoxic agents in the Journal of Oncology Pharmacy Practice, and identified 4 levels of protection (Table 2).6 Using these levels as guides, safety standards can be better determined by healthcare facilities and practices; there should be every attempt to meet these standards at the highest level possible.

Table

Preparation, administration, and disposal of intravenous (IV) chemotherapy agents pose the highest risks for accidental exposure to hazardous drugs.2 These activities involve a high frequency of handling, including accessing vials, preparing bags and syringes, handling and accessing IV sets and tubing, and discarding excess material into waste receptacles. People handling chemotherapy drugs should be provided with personal protective equipment (PPE) to protect them from exposure.6 PPE consists of chemotherapy-tested gloves, impermeable gowns, protective eyewear, and respiratory protection.7

During compounding, preparation, administration, and disconnection, the risk for exposure as a result of spills, leaks, sprays, and drips is greatest. These activities involve opening, transferring, connecting, and disconnecting, which are activities that may cause a spray, splash, or drip. Using PPE provides contact and inhalation prevention for the person handling the chemotherapy drugs in this way. However, PPE does not protect the environment and surrounding workspace from exposure. Contamination of surface areas near and far from where chemotherapy drugs are prepared and administered have been well-documented.8

If contaminants are spread via drips, spills, or transfer contact, this can result in patient, visitor, colleague, or passerby exposure to hazardous drugs. A small drop or spray will most likely go unseen. Contamination on a bedside table can easily transfer to a patient’s hands. When a patient uses a call button, pen, or elevator button, contamination can spread away from the treatment area. As a result, people who are not involved with chemotherapy administration or dispensing may also become contaminated. Hon and colleagues described job categories and associated tasks that have the potential for dermal exposure because of contaminated surfaces.9 This is of particular concern, because many people who frequently interact with patients receiving chemotherapy (eg, dietitians, clinic or medical assistants, unit clerks, and volunteers) may not be aware of the risk of exposure to hazardous drugs in this way. Other people, such as visitors, could also become contaminated by this unseen contact trail.

Knowing that these activities can pose risks for exposure, the ONS, NIOSH, and USP have identified the use of closed-system drug transfer devices (CSTDs) that can decrease or eliminate contamination.4,5,7 Since the introduction of PhaSeal (Becton, Dickinson and Company; Franklin Lakes, NJ) in 1998, studies have shown that using CSTDs prevents the drug from leaking into the environment, and protects healthcare professionals handling hazardous drugs from potential exposure.10 In that time, other devices have entered the market, affording variety in pricing and compatibility with IV and syringe products. Massoomi also described the properties of these devices, which lend themselves to reducing exposure risk. These properties, which vary to some degree from device to device, include containment, pressure equalization, syringe safety features, integration with IV delivery systems, integration with compounding automation, and device-to-vial and device-to-device interfaces.

Over the years, the ONS and USP have recommended using CSTDs when available.7 The newly published USP Chapter 800 (Hazardous Drugs—Handling in Healthcare Settings) takes effect in July 2018; this chapter purports more stringent use of safety devices and measures.11 The USP guidelines tend to address compounding and handling processes, but also refer to handling and manipulation related to administration.12 For nurses, these changes involve using CSTDs, double gloves, and the limited manipulation oral agents.5

The 2015 ONS publication “Ensuring Healthcare Worker Safety When Handling Hazardous Drugs” is a joint statement with ASCO and the Hematology/Oncology Pharmacy Association.13 Expanding on concepts identified in the ONS/ASCO guidelines, it outlines a united agreement on establishment of policies and procedures, engineering controls, PPE use, education and competency, and patient and caregiver education. It also identifies the rights of staff who are attempting to conceive or are pregnant or nursing to work in an alternate setting that would prevent exposure to hazardous drugs. Lastly, the societies agreed to continue seeking measures to further reduce the risks associated with handling these agents.

Implications of USP 800 for Nurses

The following standards are not necessarily new to chemotherapy preparation or administration processes, but have historically been recommended rather than required.

Closed-System Drug Transfer Devices

When dosage forms allow, CSTDs must be used during administration for anti–neoplastics. When administering hazardous drugs via certain routes, ancillary devices and techniques that reduce the risks posed by open systems must be used. This means that any IV push or infusion of chemotherapy will require the use of a CSTD during preparation and administration. IV setups and administration sets should be used in ways that prevent the opening of a system once connections are made.5

Double Gloves

Administration of chemotherapy using double gloving—along with wearing impermeable, disposable gowns—has long been recommended by NIOSH and noted in the ONS Chemotherapy and Biotherapy Guidelines, and is considered best practice.5 For many nurses, this may be the most difficult practice change to embrace; it invokes the idea of poor tactile sensation, which may impair their ability to manipulate tubing sets and syringes. The use of double gloves will also require changes in the sizes that are available, because the outer set may have to be a size larger than the set beneath it.

Oral Agents

Hazardous drugs that do not require further manipulation other than counting final dosage forms may be dispensed without any additional containment requirements; these drugs should be counted carefully, and tablet and capsule forms are not to be placed in machines that automatically count or package.5 For nurses, this means that any crushing or slurry preparation must be done within the contained pharmacy environment.

The Evolution of Safe Handling

Through these guidelines and recommendations, institutions and oncology practices strive to generate safe practice policies and processes to maintain a nontoxic environment. According to Easty and colleagues, adherence to standard operating procedures, together with adequate initial and ongoing training for safe handling and administration, are vital to reducing exposure and risk potentials.14

For the nursing practice, policies and procedures for chemotherapy handling, administration, and disposal are derived from the NIOSH, ASHP, and, most notably, guidelines from the ONS7. These guidelines clearly outline the “what and when” of PPE; for administration, this includes a double pair of chemotherapy-tested gloves, an impermeable, lint-free gown, and, if necessary, eye and respiratory masks for avoiding inhalation or splashes. Because a small leak or spray may go undetected, gloves and gowns are single-use and should be discarded once administration or discarding of waste is complete. Other safety measures include preparing IV drugs with tubing that has been attached and primed with diluent, using CSTDs (if available), designating storage sites, and adhering to proper storage, labeling, and transport techniques.

The most recent version of the ASCO/ONS Che­motherapy Administration Safety Standards outlines education and preparation requirements for those ordering and administering chemotherapy.3 This includes using a comprehensive educational program, and competency assessment regarding all aspects of chemotherapy administration, including safe handling of hazardous drugs. It is recommended that this be done as soon as a person is hired, and that there be annual competency reassessments.

Why Do Barriers to Safe Practice Still Exist?

In a survey of nurses and pharmacists conducted by Panoramic Healthcare Communications, awareness of the risks of hazardous drug exposure was very high, ranging from 95% to 97%.15 This included knowledge of acute risks (eg, contact dermatitis, hair loss, nasal sores), adverse reproductive outcomes, and increased risk for cancer. Awareness of policies was highest for ONS among nurses, and USP 797 among pharmacists; 60% to 70% of both groups were aware of NIOSH guidelines, and policies from the ASHP were also highly cited. More than 70% of participants in both groups reported observation of practice as the method for assessing adherence to safety handling policies. Regarding the use of CSTDs, 27% of pharmacists and 19% of nurses reported that they do not use them at their facilities, with costs being cited as the strongest reason for this disuse. Interestingly, although all participants reported using some PPE—gloves and gowns in particular—most did not meet the NIOSH recommendations for double gloves or face protection.

Despite acknowledging the risks associated with exposure to hazardous drugs, it would seem that nurses and pharmacists minimize actual risk, which is reflected in the lower rates of reported fully compliant PPE use. Respondents to the survey conducted by Panoramic Healthcare Communications are not categorized by age. When discussing safety practices surrounding chemotherapy drug handling, the more experienced nurses frequently regard safety measures as less important. Younger nurses—particularly those of childbearing age—tend to be most compliant with the use of PPE. For some of the nurses who have been in practice since prior to the inception of some of these standards and guidelines, there may still be the notion of, “It can’t happen to me,” or that the inconvenience of gowning or double gloving is not worth the effort.16

Monitoring

In addition to observation and feedback measures for enforcing the proper use of PPE and other practice standards related to chemotherapy handling, there are methods for measuring the presence of these hazardous drugs in the environment, and through biological testing of staff members.8 Surface testing can identify areas of contamination that may, in turn, measure cleaning effectiveness.14 Although medical surveillance is regarded as controversial, or a double-edged sword, it can be beneficial not just as a measure of adherence, but to provide early detection of possible health concerns.17 This type of surveillance is recommended by the NIOSH for all workers who handle hazardous materials. Measures can be taken for early detection of failures to prevent exposure, and to reduce or prevent further exposure. This could include change of work environment for the employee, but also evaluation and decontamination of an area. Medical surveillance programs can also include medical/reproductive histories, physical exams, laboratory studies, and biological monitoring of healthcare workers handling hazardous materials.

In October 2014, Dynan and I reported the processes involving education, monitoring, and reporting of compliance with PPE at our own facility.18 Over a 4-year period of tracking education, re-education, involvement of staff in product selection, and performance feedback, monitoring data have consistently been above the 90% mark for adherence to PPE.

In April 2015, Friese and colleagues began a cluster, randomized controlled trial of nurses who administer chemotherapy.19 The aims of the study include evaluating the efficacy of an audit and feedback intervention to improve use of PPE; determining whether the intervention effects on PPE use are mediated by knowledge about PPE use and perceived risk of hazardous drug exposure; and determining whether the intervention effects on PPE use are moderated by personal and organizational factors. The primary end point will be optimal use of PPE. This 4-year study, DEFENS-Drug Exposure Feedback and Education for Nurses’ Safety, will compare data collected at onset and after 18 months. Data regarding management and exposure, including blood sampling, will also be collected in the event of any chemotherapy drug spills.19

Conclusion

Although there has been some evolution in the safe-handling practices of hazardous drugs since 1979, ensuring the safety of those who handle chemotherapy is not an option, it is a requirement; thus, the evolution continues. Access to knowledge, safety products, PPE, and administration configurations are greater, but may still be limited in certain settings, such as private practices. As more information becomes available about new agents and biologics, more refined recommendations will emerge.

Reviewing the literature, talking to colleagues, and seeing nursing practice over the years, it has sometimes seemed like people acted as though they had the choice to be compliant. Enforcement of policy, reinforcement of education, and monitoring for compliance can demonstrate to workers that their safety and practice is important and expected. Compliance should not be an option.

Those who handle chemotherapy must continue to be included in the establishment of safe practice policies and procedures; their inclusion in product trials and evaluations is also key to the “buy in.” Further investigation of the generational differences in these practices may prove helpful in the education and reinforcement of hazardous drug handling, and exposure risk policies and procedures.

References

  1. Falck K, Gröhn P, Sorsa M, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet. 1979;1:1250-1251.
  2. US Department of Health & Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf. Published September 2004. Accessed February 24, 2016.
  3. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(suppl 2):5s-13s.
  4. US Department of Health & Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2014. www.cdc.gov/niosh/docs/2014-138/pdfs/2014-138_v3.pdf. Published September 2014. Accessed February 24, 2016.
  5. United States Pharmacopeial Convention. <800> Hazardous Drugs—Handling in Healthcare Settings. www.usp.org/sites/default/files/usp_pdf/EN/m7808_pre-post.pdf. Updated December 1, 2014. Accessed February 25, 2016.
  6. International Society of Oncology Pharmacy Practitioners Standards Committee. ISOPP standards of practice. Safe handling of cytotoxics. J Oncol Pharm Pract. 2007;13(suppl):1-81.
  7. Polovich M, Osen M, LeFebvre K. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 4th ed. Pittsburgh, PA: Oncology Nursing Society; 2014.
  8. 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;17:39-48.
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  10. Massoomi F. The evolution of the CSTD. Pharmacy Purchas Prod. 2015;12:S1-S12.
  11. United States Pharmacopeial Convention. Commentary. General chapter Hazardous Drugs—Handling in Healthcare Settings USP 39–NF 34, first supplement. www.usp.org/sites/default/files/usp_pdf/EN/USPNF/usp-nf-commentary/gc__800_commentary_final.pdf. Published February 1, 2016. Accessed February 25, 2016.
  12. Eisenberg S. Hazardous drug handling in light of USP <800>. Pharmacy Purchas Prod. 2015;12:18-19.
  13. Oncology Nursing Society. Ensuring healthcare worker safety when handling hazardous drugs. Oncol Nurs Forum. 2015;42:217-218.
  14. Easty AC, Coakley N, Cheng R, et al. Safe handling of cytotoxics: guideline recommendations. Curr Oncol. 2015;22:e27-e37.
  15. Higgins J, Parsons G, Faulkner S. HD handling survey results. 2015 Aug. Presented by Panoramic Healthcare Communications. Accessed May 10, 2016.
  16. Mahar K. Practical applications: overcoming barriers to chemotherapy safety in nursing. The Oncology Nurse-APN/PA. 2008;1(Suppl):2.
  17. US Department of Health & Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. Workplace solutions: medical surveillance for healthcare workers exposed to hazardous drugs. www.cdc.gov/niosh/docs/wp-solutions/2013-103/pdfs/2013-103.pdf. Published November 2012. Accessed February 24, 2016.
  18. Hennessy KA, Dynan J. Improving compliance with personal protective equipment use through the model for improvement and staff champions. Clin J Oncol Nurs. 2014;18:497-500.
  19. Friese CR, Mendelsohn-Victor K, Wen B, et al. DEFENS-Drug Exposure Feedback and Education for Nurses’ Safety: study protocol for a randomized controlled trial. Trials. 2015;16:171.
Last modified: May 23, 2016