Chemotherapy: Current and Emerging Issues in Safe Handling of Antineoplastic and Other Hazardous Drugs

The toxic effects and safe handling of hazardous drugs are issues of major concern to healthcare professionals. In previous articles, Roussel and Connor have covered the adverse health effects of hazardous drugs, contamination of the workplace, and biomarkers of effect and exposure.^1-3 This article addresses several emerging issues that healthcare providers will need to be aware of, including hazardous drug assessment, use of antineoplastic drugs in nononcology settings, oral chemotherapy, decontamination/cleaning, state legislative activities, and US Pharmacopeial Convention (USP) Chapter 800.⁴

The clinical utility of hazardous drugs is expanding rapidly, and new challenges are arising for their safe use and handling. Occupational safety and health organizations and healthcare professionals are working hard to create safety guidance documents that keep pace with the changing environment. The growing use of hazardous drugs in nononcology practices and the increased utilization of oral hazardous drugs require the scope of safe handling practices to extend beyond traditional settings. The promulgation of new legislation related to safe handling of hazardous drugs by several states has forever changed the climate in which safe handling guidelines have been perceived. With the revamped USP Chapter 800 for hazardous drug compounding, oncology pharmacists’ and nurses’ unique skill sets should be shared beyond their disciplines.

Historically, safe handling guidance documents have been recommendations that are only followed on a voluntary basis. Occupational Safety and Health Administration (OSHA) inspections are infrequent and generally conducted only in response to reports of violations. However, states like Washington,⁵ California,⁶ and North Carolina⁷ are leading the charge in establishing state laws for the safe handling of hazardous drugs with consequences for when they are not followed. With guidance from OSHA,⁸ the National Institute for Occupational Safety and Health (NIOSH),9 the American Society of Health-System Pharmacists,¹⁰ the Oncology Nursing Society,¹¹ and USP,¹² it is important for senior management in hospitals and private oncology practices, and for owners and managers of retail pharmacies, to perceive this information as mandatory requirements to ensure employee protection. While implementation of medical surveillance may meet with greater resistance, proper policies for the identification and labeling of hazardous drugs, as well as adequate facilities, equipment, and personal protective equipment (PPE), should be clear in standard operating procedures. The hope is that this article challenges the oncology community to reach out to other practice sites where hazardous drugs are handled and share the safety practices that have evolved over the past few decades.

Table 1

The Risk of Hazardous Drugs
The healthcare setting has the largest and most diverse mix of chemicals that are hazardous to humans—more than any other occupational setting—ranging from drugs with acute effects to those linked to reproductive toxicity and cancer.¹³ Surface contamination with hazardous drugs in pharmacies and nursing administration areas has been extensively documented.² Considering that the existing literature has only evaluated the presence of less than 5% of the known hazardous drugs found in the healthcare workplace, the incidence and magnitude of surface contamination are likely higher. The main vector of exposure is dermal contact directly with drugs and drug packaging (documented to be as high as 100% contaminated when leaving the manufacturer) and through indirect contact by touching surfaces that have been contaminated.¹⁴ Additional routes of exposure include inhalation (breathing contaminated aerosols and vapors), ingestion via hand-to-mouth contact (eating, drinking, gum chewing) in areas where hazardous drugs are stored or compounded, and injection (finger sticks, vial breakage).¹⁵

Of greater concern than the presence of hazardous drugs in the work environment is documentation that the drugs and their metabolites have been found in the urine of exposed healthcare workers.³ Similarly, studies of worker exposure have only been conducted on a small percentage of hazardous drugs, and positive urine samples have been detected in pharmacists, pharmacy technicians, and nurses, including those not directly involved in compounding.³ Some investigations into biomarkers of effect have shown associations between surface contamination and the presence of drugs in the urine,^16-18 while others have demonstrated significant associations between exposure and biomarkers of genotoxicity in exposed healthcare workers.³

Hazardous Drug Identification and Hazard Assessment
The first step in any safe handling program is the identification and risk assessment of hazardous drugs in any given workplace. It is recommended to start the process by examining NIOSH’s Hazardous Drug List, but institutions can and should create their own facility-specific list based on their current drug usage. The NIOSH list was last updated in June 2012,13 and the proposed changes for the 2014 update include the addition of several oral agents (eg, erlotinib, fluconazole, spironolactone, topiramate, warfarin).¹⁹ Institutions in which hazardous drugs are present should have a mechanism for updating their list as new drugs come into the facility.

There are many variations for further categorizing hazardous drugs, with some institutions separating antineoplastic drugs from hazardous drugs with precautions similar to those for the antineoplastic drugs and grouping together teratogens, reproductive toxins, and hormones.^20-22 Some facilities further separate risk levels by formulation, using different precautions and PPE when handling hazardous intravenous drugs compared with hazardous oral drugs, and even determining which drugs should be counted or manipulated within a biological safety cabinet (BSC) versus oral drugs that have been classified as safe to be handled in the general environment as long as the dosage form is not altered.

Both USP Chapter 8004 and OSHA’s Technical Manual8 acknowledge that dispensing nonantineoplastic hazardous drugs in unit-dose and unit-of-use dosage forms that are not altered (cut, crushed, etc) likely does not impart significant risk to the employee. To better address these and other issues, NIOSH has proposed listing hazardous drugs in 3 categories: (1) antineoplastic drugs (based on American Hospital Formulary Service classification 10:00), (2) nonantineoplastic drugs, and (3) drugs primarily with reproductive risks. Along with these changes, NIOSH will also provide additional guidance on engineering controls and PPE.¹⁹

In hospitals and cancer centers, pharmacists can provide knowledge about pharmacology, dosage formulation, and compounding, while nurses can address administration concerns and patient-specific issues that have required process and administration changes at the bedside. A team approach can enhance the ability to evaluate all aspects of a drug and its potential risks, from receiving to preparation, administration, disposal, and patient excretion. The risk stratification approach to hazardous drug handling may increase compliance by targeting the medications and situations most likely to cause the greatest exposure and risk to the employee.

Use of Antineoplastic Drugs in Nononcology Settings
Cancer patients are not the only patients being treated with antineoplastic drugs.^23,24 Many drugs that have typically been considered just for the treatment of cancer are now being used in other specialties (Table 1). As Polovich and Giesker noted in 2011, “Oncology units where patients with cancer receive chemotherapy are not the only settings where hazardous drugs are found. Because of the increased use of antineoplastic agents for nononcology indications, nurses’ risk for occupational exposure is distributed more widely than in the past.”²³

Often, healthcare professionals who are administering antineoplastic drugs in other settings may not be aware of their potential occupational hazards and/or may not be adequately trained in their use and disposal. General inpatient units in hospitals, as well as procedural areas such as the surgery department and interventional radiology, may manage hazardous drugs as only a small percentage of total patient care activities; thus, these handling activities may be associated with less robust procedures and staff education as well as decreased access to appropriate equipment or supplies for safe handling and disposal. Oncology pharmacists and nurses have valuable insight and can help inpatient and procedural areas perform a gap analysis, develop standardized processes, and share knowledge gained from experience. Sharing up-to-date regulatory documents and employing face-to-face collaborative approaches to reviewing existing policies related to the safe handling and administration of hazardous drugs are hugely beneficial for institutions as a whole.

With the increased prescribing of hazardous drugs for nononcology conditions, retail pharmacies often carry many solid dosage forms of NIOSH-listed drugs, some of which are uncoated pressed-powder tablets that easily liberate hazardous drug powder onto the work surface or into the air. Retail pharmacies often purchase large stock bottles of medications, and the dust liberated in production and transportation accumulates in the bottom of the bottles. Inverting a stock bottle of uncoated tablets to get them out often leads to spilling powder and sending it into the air. The range of hazardous drugs in retail chains is increasing as a result of expanding their scope of services in an effort to increase revenue and remain competitive, including special ordering medications to help loyal customers. While few retail pharmacies may believe they carry many hazardous drugs, about 10% of the top 100 drugs in the United States either by sales or number of units dispensed from 2013 to 2014 are listed as hazardous by NIOSH.^13,14,25

Prefilled syringes of hormonal-modulating and immunotherapy agents as well as injectable vials of methotrexate can be found on the shelves of retail pharmacies. In the busy retail pharmacy environment, staffs traditionally wear minimal to no PPE, and the positions of retail pharmacy technicians are predominantly staffed by a younger workforce with a relatively high turnover rate. This reinforces the fact that it is crucial for all healthcare settings and pharmacies to identify and label hazardous drugs and to properly educate staff.

Table 2

Oral Chemotherapy/Nonliquid Hazardous Drugs
The guidelines from several organizations^8-12 state that hazardous drugs in solid dosage forms pose a health risk to employees. The level of risk varies depending on the formulation. The highest-risk formulation is uncoated pressed-powder tablets that liberate dust particles, causing surface contamination and creating airborne drug dust that can be directly inhaled by employees and can contaminate the work area.⁸ Capsules and coated tablets are unlikely to produce dust unless broken in handling or if they are crushed or cut, which can pose a risk for surface contamination.

OSHA’s Technical Manual states: The handling of nonliquid forms of HD’s [hazardous drugs] requires special precautions as well. Tablets which may produce dust or potential exposure to the handler should be counted in a BSC. Capsules, i.e., gel-caps or coated tablets, are unlikely to produce dust unless broken in handling. These are counted in a BSC on equipment designated for HD’s only, because even manual counting devices may be covered with dust from the drugs handled. Automated counting machines should not be used unless an enclosed process isolates the hazard from the employee(s).⁸

While many retail pharmacies have separate counting trays for penicillin and other β-lactam drugs, many pharmacies do not have separate counting trays for hazardous oral drugs, let alone have negative pressure rooms with externally vented BSCs. Common examples of hazardous drugs dispensed in most pharmacies in uncoated pressed β-powder formulation include generic cyclophosphamide, methotrexate, melphalan, 6-mercaptopurine, and others.²⁶

When finalized, USP Chapter 800 will provide additional information detailing the dispensing of hazardous drug dosage forms not requiring alteration: HDs in unit-dose or unit-of-dose packaging that do not require any further alteration before delivery to the patient or the patient’s caregiver may be dispensed without any further requirements for containment unless required by the manufacturer.

If the entity’s SOPs [standard operating procedures] permit, non-antineoplastic HDs that require only transfer from the manufacturer’s package to a prescription container may be dispensed without any further requirements for containment unless required by the manufacturer. Counting of HDs should be done carefully, and clean equipment should be dedicated for use with these drugs.⁴

The finalized USP Chapter 800 will state that tablet and capsule forms of HDs shall not be placed in automated counting machines, as mechanical stress may damage the dosage form and introduce powdered contaminants into the work area. “Counting coated tablets and capsules does not require a C-PEC [containment primary engineering control], as long as they are not altered or broken.”⁴

The oral route of administration for hazardous drugs has become increasingly more common, with 25% of the oncology drug pipeline intended for oral self-administration.²⁷ Retail pharmacies, specialty pharmacies, and physician practices with in-house dispensaries must think about safe handling from a different perspective. Recently, several documents have been published with a focus on oral chemotherapy.^28-34 While standards of practice dictate that nurses administering intravenous chemotherapy should have specific qualifications (such as additional training, passing facility-specific competencies, and preferably the Oncology Nursing Society Chemotherapy Biotherapy Certificate), currently no additional requirements are recommended for nurses administering oral hazardous drugs.²⁷ Patients and caregivers must also be educated about the safe handling of hazardous drugs while self-administering in the home, such as wearing gloves during administration of drugs, handling patient waste and changing diapers, proper storage of drugs, and disposal of waste materials. Parents who may be administering liquid formulations of hazardous drugs to their children (potentially for years) must be educated about how to protect themselves and other members of the household. In addition to safety recommendations for oral chemotherapy, both for patient education and healthcare practitioners, Goodin and colleagues³⁰ made recommendations to drug manufacturers. To reduce the possibility of exposure for healthcare personnel and family members or other caregivers, the authors recommended either dispensing oral hazardous drugs in more appropriately sized packages to better approximate treatment cycles or considering unit-dose packaging with the goal of minimizing product manipulation during dispensing.

Special consideration should also be paid to mail order pharmacies and other facilities that use automated dispensing machines for both nonhazardous and hazardous drugs in pill form, as these tend to produce dust, which can be inhaled by workers and contaminate surfaces, which can lead to dermal uptake.^35-37

Table 3

Decontamination and Cleaning of Surfaces Contaminated With Hazardous Drug Residues
USP Chapter 79712 defines decontamination as “inactivation, neutralization, or removal of hazardous drugs, usually by chemical means,” whereas deactivation is the “treatment of a hazardous drug with another chemical, heat, ultraviolet lights, or other agent to create a less hazardous agent.” Cleaning is described as “the removal of soil (e.g., organic and inorganic material) from objects and surfaces normally accomplished manually or mechanically using water with detergents or enzymatic products.” Often these terms are used interchangeably and incorrectly. Given the large number of hazardous drugs in use and the wide variation in their chemical nature and makeup, no single agent will successfully decontaminate or clean surfaces after exposure to most of these drugs.^38-45 Sodium hypochlorite (bleach) is probably used most often for decontamination. Bleach is a strong oxidizer shown to deactivate some hazardous drugs. The availability of commercial products such as Surface Safe (Hospira Healthcare Corporation, Saint-Laurent, Quebec, Canada; http://www.hospira.ca/english/surfacesafe.aspx) and HDClean (ChemoGLO, LLC, Chapel Hill, North Carolina; http://www.che
moglo.com/WhatIsHDClean.aspx) has increased convenience, but they have only been validated with a small number of drugs and may be cost prohibitive in some facilities. The 2-part Surface Safe decontamination product contains bleach as the first step and sodium thiosulfate as a neutralizer for the second step; HDClean is a proprietary blend of quaternary ammonium compounds. It should be noted that using isopropyl alcohol to disinfect a BSC will not decontaminate any hazardous drugs, but rather could put the drug into solution, and the wiping process may result in the spread of contamination.¹⁰

Decontamination procedures are vital safety measures in any facility that handles hazardous drugs. While the process and frequency were previously not well defined in US documents,^8,9 USP Chapter 800 provides more detailed guidance, and it is expected that more information will be released within the next few years as the data documenting surface contamination continue to accumulate.

Important considerations for decontamination of BSCs include donning full PPE and ensuring proper ventilation. While it is ideal for the sash of the BSC to remain down during decontamination, often it is necessary to lift the sash of the BSC; thus, employees must wear a respirator such as an N-95 (not a surgical mask). USP Chapter 800 mentions the importance of performing cleaning in areas that are sufficiently ventilated, but does not provide further detail. Because there is a risk of hazardous vapors generated by liberating hazardous drugs or from cleaning agents, the exhaust fan and blower of the BSC must always remain on during the decontamination process to maintain exhaust.8 A BSC should be decontaminated at least weekly, as well as prior to environmental maintenance and certification, after a chemotherapy spill or if contamination is suspected, and after any interruption in ventilation occurs.

Cleaning with water and an alkaline detergent, followed by thorough rinsing, is also an acceptable method when the physical situation permits, as hazardous residue would be liberated and then rinsed away.⁸ All waste material generated during decontamination is considered hazardous and should be discarded in appropriate waste containers. Using spray bottles inside BSCs should be avoided, owing to effects on HEPA filters and the production of aerosols. The final step before compounding is to wipe down the BSC with alcohol to reestablish sterility. Cleaning and disinfection of the hood should be conducted per USP 797.¹² Surface decontamination is also appropriate for pharmacy counters with hazardous drug traffic as well as nursing areas where chemotherapy is administered.

State Legislative Activities Related to Hazardous Drugs
In response to the growing concern about healthcare workers being exposed to hazardous drugs during the course of their working life and the wealth of new information being published internationally in the literature, several states have enacted, or are in the process of enacting, legislation aimed at protecting workers from the adverse effects of antineoplastic and other hazardous drugs. Most legislation is based on the guidelines published by NIOSH in 2004.⁹ Table 2 summarizes the current activities at the state level.

Washington State
In 2011, the Washington State legislature passed a bill requiring the Department of Labor & Industries to adopt rules for the safe handling of hazardous drugs.⁵ The legislation stated the following: Pursuant to RCW 49.17.465, the department is required to ‘adopt by rule requirements for the handling of antineoplastic and other hazardous drugs in health care facilities regardless of the setting.’ The statute requires the department’s rules ‘be consistent with and not exceed provisions adopted by the National Institute for Occupational Safety and Health’s (NIOSH) 2004 alert on preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings as updated in 2010.’…The legislature also directed the department to consider input from hospitals, organizations representing health care personnel, other stakeholders in adopting the rules.⁴⁶

Adopted on January 3, 2012, the hazardous drugs rule requires employers to develop and implement a written hazardous drugs control program to protect workers if there is a reasonably anticipated occupational exposure to one or more hazardous drugs. Washington State adopted the NIOSH definition of hazardous drugs and the NIOSH Hazardous Drug List for its documents. The program is being implemented in stages, and as of the start of 2015, employers must have completed and implemented a written hazardous drugs control program. Employee training must be implemented by July 2015, and, finally, appropriate ventilated cabinets must be installed by January 2016.

All healthcare facilities where employees face occupational exposure must comply, including hospitals, clinics, nursing homes, laboratories, offices, veterinary medicine clinics, retail pharmacies, home healthcare agencies, and research laboratories where a healthcare provider offers healthcare to patients. The rule allows for alternative precautions when the hazard assessment determines a low occupational exposure risk while preparing hazardous drugs other than chemotherapy agents, for example, from crushing and splitting tablets or drawing drug into a syringe. These alternatives could include temporarily designating a space as the preparation area, using appropriate PPE, and instituting specific cleaning procedures. The Washington State Division of Occupational Safety & Health has created a Hazardous Drugs Advisory Committee to aid employers in implementation of the requirements by discussing new NIOSH recommendations, scientific and technological developments, and other issues related to implementing this rule, via live meetings, a hazardous drugs webpage for resources, and a hazardous drugs email listserv.⁴⁷

Washington State’s hazardous drugs rule does not include medical surveillance in the final document, as the topic was removed from the proposed rule because of concerns that NIOSH was updating its statements on the topic during the drafting process. Washington State’s written hazardous drugs control program specifies a list of elements that must be addressed and must include worker input during the creation process (Table 3).

Healthcare and other workers potentially impacted by the Washington State rule include all those who work in areas where hazardous drugs are handled
(Table 4).

California
The Cal/OSHA Occupational Exposure to Antineoplastic Drugs Advisory Meeting in June 2014 discussed implementation of Assembly Bill (AB) 1202 and Labor Section 144.8 regarding occupational safety and health standards: hazardous drugs. The California bill refers only to antineoplastic drugs and not all hazardous drugs.^6,48 The language noted: It is the intent of the Legislature to require the Occupational Safety and Health Standards Board to adopt standards consistent with the NIOSH alert regardless of setting in order to protect health care personnel from hazardous exposure to these drugs.

The board shall adopt an occupational safety and health standard for the handling of antineoplastic drugs in health care facilities regardless of the setting. In developing the standard, the board shall consider input from hospitals, practicing physicians from impacted specialties, including oncology, organizations representing health care personnel, including registered nurses and pharmacists, and other stakeholders, and shall determine a reasonable time for facilities to implement new requirements imposed by the adopted standard. The standard, to the extent feasible, shall be consistent with and not exceed recommendations in the NIOSH 2004 alert entitled ‘Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings,’ as updated in 2010. The standard may incorporate applicable updates and changes to NIOSH guidelines.

North Carolina
The state of North Carolina is currently debating the bill in the Senate, after being passed by the House in 2013.⁷ Whereas, in this alert, the NIOSH presents a standard precautions or universal precautions approach to handling hazardous drugs safely, meaning that it recommends that all hazardous drugs be handled as outlined in the alert; Now, therefore, The General Assembly of North Carolina enacts: The General Assembly finds that health care personnel who work with or near hazardous drugs in health care settings may be exposed to these agents in the air, on work surfaces, clothing, and medical equipment or through patient contact. It is the intent of the General Assembly to require health care facilities to follow rules requiring compliance with all aspects of alerts from the National Institute for Occupational Safety and Health regardless of the setting in order to protect health care personnel in this State from hazardous exposure to such drugs.

USP Chapter 800
An important new development related to the safe handling of hazardous drugs is the new USP chapter, Hazardous Drugs—Handling in Healthcare Settings, which was recently available for public comment. Chapter 8004 will supersede the hazardous drug section in USP Chapter 7979 (http://www.usp.org/usp-nf/notices/compounding-notice). Because Chapter 800 will be enforced by some state boards of pharmacy, it will have an impact on the preparation/compounding of hazardous drugs.

Summary
With new challenges to both employees and employers to ensure a safe working environment when antineoplastic and other hazardous drugs are present, it will be imperative that all parties are aware of new recommendations and regulations that will affect their work practices. Washington State and California already have legislation focused on the safe handling of hazardous drugs, and other states are following close behind with their own legislation or regulations. As NIOSH, USP, and other organizations move forward on activities aimed at protecting workers from hazardous drugs, healthcare workers everywhere will benefit from safer working conditions in their endeavors to treat seriously ill patients with an ever expanding armament of drugs.

Table 4

References
1. Roussel C, Connor TH. Chemotherapy and pharmacy: a toxic mix? Oncol Pharmacist. 2013;6(2):1, 32-33.
2. Roussel C, Connor TH. Chemotherapy: every step you take, every move you make…. Oncol Pharmacist. 2013;6(4):1, 8-12.
3. Roussel C, Connor TH. Chemotherapy: biomarkers of exposure, effect, reproductive hazards and cancer. Oncol Pharmacist. 2014;7(1):1, 10-13, 18.
4. US Pharmacopeial Convention. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. http://www.usp.org/usp-nf/notices/compounding-notice. Accessed June 20, 2014.
5. Washington State Senate Bill 5594. 62nd Leg, 2011 Regular Session. http://apps.leg.wa.gov/documents/billdocs/2011-12/Pdf/Bills/Senate%20Bills/5594.pdf. Accessed June 20, 2014.
6. California Assembly Bill 1202. 2013-2014 Regular Session. http://openstates.org/ca/bills/20132014/AB1 202/. Accessed June 20, 2014.
7. North Carolina House Bill 644. 2013-2014 Regular Session. http://www.ncleg.net/gascripts/BillLookUp/BillLookUp.pl?Session=2013&BillID=h644. Accessed June 20, 2014.
8. Occupational Safety and Health Administration. Controlling occupational exposure to hazardous drugs. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html. Published January 20, 1999. Accessed June 20, 2014.
9. 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/. Published September 2004. Accessed June 20, 2014.
10. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;63:1172-1193.
11. Polovich M, Bolton DL, Eisenberg S, et al, eds. Safe Handling of Hazardous Drugs. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2011.
12. US Pharmacopeial Convention. Revised Chapter <797> Pharmaceutical Compounding—Sterile Preparations. http://www.pbm.va.gov/linksotherresources/docs/USP797PharmaceuticalCompoundingSterileCompounding.pdf. Accessed July 15, 2014.
13. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012. DHHS (NIOSH) Publication No. 2012-150. http://www.cdc.gov/niosh/docs/2012-150/. Published June 2012. Accessed June 20, 2014.
14. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health Syst Pharm. 2005;62:475-484.
15. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Personal Protective Equipment for Health Care Workers Who Work With Hazardous Drugs. DHHS (NIOSH) Publication No. 2009-106. http://www.cdc.gov/niosh/docs/wp-solu
tions/2009-106/pdfs/2009-106.pdf. Published October 2008. Accessed June 20, 2014.
16. Pethran A, Schierl R, Hauff K, et al. Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health. 2003;76(1):5-10.
17. Connor TH, DeBord G, Pretty JR, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52:1019-1027.
18. Villarini M, Dominici L, Piccinini R, et al. Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis. 2011;26(3):359-369.
19. 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. DHHS (NIOSH) Publication No. 2014-xxx [In preparation]. http://www.cdc.gov/niosh/topics/hazdrug/. Accessed July 15, 2014.
20. Chaffee BW, Armistead JA, Benjamin BE, et al. Guidelines for the safe handling of hazardous drugs: consensus recommendations. Am J Health Syst Pharm. 2010;67(18):1545-1546.
21. Badry N, Fabbro J, de Lemos ML. Hazards in determining whether a drug is hazardous [published online ahead of print August 20, 2013]. J Oncol Pharm Pract. doi:10.1177/1078155213496675.
22. Kaestli L-Z, Fonzo-Christe C, Bonfillon C, et al. Development of a standardised method to recommend protective measures to handle hazardous drugs in hospitals. Eur J Hosp Pharm. 2013;20(2):100-105.
23. Polovich M, Giesker KE. Occupational hazardous drug exposure among non-oncology nurses. Medsurg Nurs. 2011;20(2):79-85, 97.
24. Menonna-Quinn D. Safe handling of chemotherapeutic agents in the treatment of nonmalignant diseases. J Infus Nurs. 2013;36(3):198-204.
25. Drugs.com. U.S. pharmaceutical sales - Q4 2013. http://www.drugs.com/stats/top100/sales. Updated February 2014. Accessed July 15, 2014.
26. Drug Information Handbook. 23rd ed. Hudson, OH: Lexi-Comp, Inc; 2014.
27. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(suppl 2):S5-S13.
28. Griffin E. Safety considerations and safe handling of oral chemotherapy agents. Clin J Oncol Nurs. 2003;7(suppl 6):25-29.
29. Simmons CC. Oral chemotherapeutic drugs: handle with care. Nursing. 2010;40(7):44-47.
30. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract. 2011;7(1):7-12.
31. Meier K, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents: a European perspective. Eur J Oncol Pharm. 2011;5(2):4-10.
32. McLauchlan R. Safe dispensing of oral chemotherapy. Safety Considerations Oncol Pharm. Fall 2011 (special ed).
33. Wakui N, Ookubo T, Iwasaki Y, et al. Development of a closed drug preparation method for oral anticancer drugs. J Oncol Pharm Pract. 2013;19(4):315-320.
34. Si P, Chan A. Common toxicities of oral anticancer agents: an overview. Safety Considerations Oncol Pharm. Fall 2011 (special ed).
35. Fent KW, Durgam S, Aristeguieta C, et al; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Report: Exposures to Pharmaceutical Dust at a Mail Order Pharmacy—Illinois. http://www.cdc.gov/niosh/hhe/reports/pdfs/2010-0026-3150.pdf. NIOSH HETA no. 2010-0026-3150. Published December 2011. Accessed June 20, 2014.
36. Fent KW, Tapp L, Wiegand D; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Program: Evaluation of Safety Climate, Health Concerns, and Pharmaceutical Dust Exposures at a Mail Order Pharmacy. Report no. 2012-0044-3199. http://www.cdc.gov/niosh/hhe/reports/pdfs/2012-0044-3199.pdf. Published December 2013. Accessed June 20, 2014.
37. Fent KW, Durgam S, Methner M; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Program: Evaluation of Pharmaceutical Dust Exposures at an Outpatient Pharmacy. Report no. 2010-0078-3177. http://www.cdc.gov/niosh/hhe/reports/pdfs/2010-0078-3177.pdf. Published April 2013. Accessed June 20, 2014.
38. Chu WC, Hon CY, Danyluk Q, et al. Pilot assessment of the antineoplastic drug contamination levels in British Columbia hospitals pre- and post-cleaning. J Oncol Pharm Pract. 2012;18(1):46-51.
39. Hon CY, Chua PP, Danyluk Q, et al. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study. J Oncol Pharm Pract. 2014;20(3):210-216.
40. Queruau Lamerie T, Nussbaumer S, Décaudin B, et al. Evaluation of decontamination efficiency of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. Ann Occup Hyg. 2013;57(4):456-469.
41. Lé LM, Jolivot PA, Sadou Yaye H, et al. Effectiveness of cleaning of workplace cytotoxic surface. Int Arch Occup Environ Health. 2013;86(3):333-341.
42. Lee S-G, Ambados F, Tkaczuk M, et al. Paclitaxel exposure and its effective decontamination. J Pharm Pract Res. 2009;39(3):181-185.
43. Roberts S, Khammo N, McDonnell G, et al. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Pract. 2006;12(2):95-104.
44. Touzin K, Bussières JF, Langlois E, et al. Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg. 2010;54(3):351-359.
45. BC Cancer Agency. BC cancer agency pharmacy practice standards for hazardous drugs. Module 1: safe handling of hazardous drugs. http://www.bccancer.bc.ca/NR/rdonlyres/2F1E0F82-D308-4E94-ABC0-1BF
1CCCE2FC3/59972/2Module1.pdf. Published January 2012. Updated April 3, 2014. Accessed June 20, 2014.
46. Washington State Dept of Labor & Industries. Concise explanatory statement: hazard drugs. Adopted January 2012; effective January 2014. http://www.lni.wa.gov/rules/AO11/10/1110CES.pdf. Accessed June 20, 2014.
47. Washington State Dept of Labor & Industries. Questions & answers about the new hazardous drugs rule. http://www.lni.wa.gov/Safety/Topics/AtoZ/Hazar
dousDrugs/qna.asp. Accessed June 20, 2014.
48. State of California Dept of Industrial Relations. Ca.gov. Web site. Cal/OSHA: Occupational exposure to neoplastic drugs advisory meeting. http://www.dir.ca.gov/dosh/doshreg/Antineoplastic-Drugs/. Accessed June 20, 2014.

---

Disclaimers
The findings and conclusions of this presentation have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy.

Mention of company names or products does not constitute endorsement by the National Institute for Occupational Safety and Health.