Pharmacists play an important role as educators, and as such must be instrumental in implementing safe practices in hazardous drug (HD) handling. The majority of HDs are antineoplastic agents, but other types of drugs, such as antiviral, immunosuppressive, and some hormonal agents, are equally harmful. Health care workers, including pharmacy staff, nurses, and others who prepare, administer, or care for patients who receive HDs, are in danger of being exposed to these chemicals during routine handling. The harmful effects of HD exposure have been reported for over thirty years, and while many guidelines exist to reduce worker exposure, the problem has persisted. To protect employees from HD exposure, effective strategies must be evaluated, developed, and implemented. 

Exposure Risks
According to the Occupational Safety and Health Administration’s (OSHA) Hazard Communication Standard, employees must be educated on hazardous chemicals in the workplace and information must be provided to staff detailing how to protect themselves from exposure, thus reducing the incidence of chemical-related occupational illness and injury. One challenge hospitals may encounter is documenting that each employee has been educated on the dangers of HDs. Utilizing a standardized template that employees sign to verify they received training and understand the risks of HD handling ensures compliance with the Hazard Communication Standard (see online-only Figure at: www.pppmag.com/riskacknowledgementform).

The serious effects of HD exposure include acute symptoms such as hair loss, abdominal pain, fatigue, nausea, nasal irritation or sores, contact dermatitis, allergic reactions, and skin and eye injury.^1-3 Adverse reproductive outcomes have been reported in several studies of nurses and pharmacists working with HDs, including fetal loss, miscarriage, and spontaneous abortions^4-7; infertility^8-10; and preterm births and learning disabilities in offspring.⁹ HD exposure also has been associated with chromosome damage in health care workers^11-14 and a higher occurrence of cancer.^15-19 

Avoiding these severe consequences can best be achieved through the development of a hospital culture of safety, including the expectation that all staff practice safe HD handling procedures consistently. Although any HD handling activity can result in worker exposure, contact occurs most commonly by absorption through the skin or mucous membranes during compounding and transferring drugs between containers, activities typically performed by pharmacists or pharmacy technicians. Nurses are prone to exposure most often during drug administration activities, such as spiking or unspiking tubing into HD-containing IV bottles or bags, priming tubing, and connecting or disconnecting syringes from injection ports. In addition, handling contaminated body fluids from patients who have been treated with HDs in the previous 48 hours represents an exposure risk for patient care staff. 

More than 30 studies have documented workplace surface contamination with HDs, and 12 studies have identified HD contamination on vial exteriors; thus, contact with contaminated surfaces is a significant source of exposure. Other routes of exposure include inhalation of aerosols or vapors, injection from sharps injuries, or unintended ingestion. Given that more than 20 studies have identified HDs and their metabolites in the urine of health care workers, clearly more must be done to reduce the incidence of health care worker exposure.



Exposure Reduction Strategies
Guidance for reducing HD exposure has been available in the United States for over 25 years from OSHA, and the American Society of Health-System Pharmacists was instrumental in developing these recommendations. The Oncology Nursing Society (ONS) also has guidelines for the safe handling of HDs, and the National Institute for Occupational Safety and Health (NIOSH) summarizes the current recommendations in its publications.

In health care organizations, a comprehensive HD safe handling program is most effectively based on factors that indicate a positive safety climate,^20-22 including four important components: 

• Existence of safety policies and procedures (P&Ps) with an expectation of compliance
• Provision of education and training in HD safe practices
• Availability of appropriate safety equipment and supplies 
• Management support for safety

Instituting Hazardous Drug Policies and Procedures
P&Ps provide effective administrative controls that have the potential to decrease hazardous exposures in the workplace—provided they are robust, comprehensive, and followed consistently by all staff handling HDs. For example, P&Ps requiring the use of personal protective equipment (PPE) have been shown to increase PPE use. When developing policies for HD handling, it is essential to consider the safety of all employees who may be exposed as a function of their work; loading dock employees, couriers, housekeepers, waste handlers, nurses, nursing assistants, pharmacists, and pharmacy technicians should all have their HD handling procedures outlined in writing. While department-level policies (eg, for pharmacy, nursing, and environmental services) that address job-specific procedures are often implemented, developing multidisciplinary P&Ps related to HD safety is equally important. Convening a safety committee may be an effective forum for developing policies that are consistent across departments and that address organization-wide issues.

Be sure to define procedures to mitigate risk throughout all drug preparation, delivery, and administration activities in P&Ps. Some of the required elements include limiting HD preparation to an area that is designated for that purpose and that has restricted access; performing compounding in a primary engineering control, such as a biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI); wearing PPE that has been tested for use with HDs; and cleaning and decontaminating work areas before and after each activity and at the end of the shift or work day, depending on volume. 

Policies also must address compliant HD IV preparation. Some of the areas that are Chapter <797>-specific to HDs include the use of appropriate engineering controls, negative pressure in the HD compounding area, separate storage for HDs, and personnel training. In addition, OSHA requires all HDs labeled as hazardous to communicate the need for precautions to those handling these medications. P&Ps should require an inventory of HDs used in the facility and a plan for its regular review and update so that pharmacy personnel can identify drugs requiring labels. 

Furthermore, P&Ps must define safe transportation methods for HDs from the pharmacy to the administration area, as well as the qualifications of those who are authorized to transport HDs. Pharmacy and nursing personnel performing these duties should be trained upon hire and then annually thereafter, and competency requirements included in the P&P. In addition, organizations may choose to limit HD administration to specific locations in an effort to minimize staff exposure. Procedures also should specify admission criteria and the approved procedure for transferring patients to designated units for HD administration during high-census periods.

Procedures must also address the various routes of HD administration, the PPE required for each, how to handle contaminated patient excreta, and how to dispose of HD waste. Eating, drinking, applying cosmetics, and other activities that might result in exposure must be prohibited in areas where HDs are stored and handled. Policies must describe housekeeping procedures for cleaning the areas where HDs are handled, including pharmacy and patient care departments. Finally, the plan for follow-up after acute employee HD exposure and a medical surveillance plan for workers must be described (see Sidebar below). Monitoring compliance with safe-handling P&Ps is essential to an effective HD safety program. Supervisors should develop a process for periodic observation of staff to document compliance and institute corrective action for noncompliance. 

Education and Training
As in any safety initiative, providing education and training to staff is integral to program success. Pharmacists have an important role as educators, not only for pharmacy staff, but also for patient care and housekeeping staff. All personnel who handle HDs must receive education and training specific to the activities for which they are responsible. This education should include the risks, routes, and possible sources of HD exposure, and procedures and equipment to minimize risk. Teach staff to recognize the labels that identify drugs requiring special handling and how to access additional information about those drugs (eg, material safety data sheets). Information about proper disposal methods for HD waste also must be provided during orientation and training. Some facilities also print disposal instructions (eg, Discard in Cytotoxic Waste Container) on medication administration records, or use a colored label on drug containers. 

Correct use of BSCs and CACIs requires training, since safety is technique-dependent. When using needles and syringes for drug compounding, certain techniques can minimize leakage from vials and ampules. One such practice is negative-pressure technique when accessing vials. Training also should include the proper use of closed system transfer devices (CSTDs), identification of appropriate PPE, selection of PPE based on specific tasks, disposal of contaminated equipment, hazardous spill clean up, and safe handling of contaminated patient waste. Provide staff with the opportunity to practice HD handling activities under supervision until they are competent in all manipulations. Checklists are useful tools for verifying and documenting competency (see Figure 1).

Click here to view a larger version of this Figure

Safety Equipment and Supplies
Safety equipment must be available and accessible in order for workers to use appropriate precautions. The equipment and supplies required for HD handling include primary engineering controls for HD compounding, two pairs of chemotherapy-tested gloves, impervious gowns, eye and face protection (when splashing is possible), respiratory protection (when aerosols or vapors are present), and designated disposal containers for HD waste. Recent studies indicate that nurses may not consistently use chemotherapy-designated gloves and gowns for HD handling. Since health care workers use PPE for various activities, they must be able to identify and access gloves and gowns that provide protection against HD exposure. 

Supplementary engineering controls, such as CSTDs, minimize leaking when transferring HDs from one container to another. Using CSTDs is vital, as they are the only engineering controls available for use during HD administration. They reduce nurses’ exposure during leak-prone activities, such as spiking IV bags, priming IV tubing, and connecting and disconnecting tubing and syringes. Several studies have documented a decrease in environmental surface contamination with HDs following the implementation of CSTDs.

Management Support for Safety
There is a high correlation between organizations’ commitment to safety and staff policy adherence. A positive workplace safety climate is a predictor of HD precaution use,²³ and HD exposure may be lower in organizations that implemented chemotherapy double checks as recommended by the American Society of Clinical Oncology (ASCO)/ONS Chemotherapy Administration Safety Standards.²⁴ Managers and supervisors can influence the use of safety equipment by providing positive feedback to workers for its use and negative feedback when it is not used. When employed consistently, this performance feedback has the potential to increase precaution use and reduce HD exposure. Characteristics of organizations that encourage safety include having safety goals, allocating resources for safety, implementing policies that promote safety, and providing safety training. 

Conclusion
HD exposure is a potential consequence of oncology practice for all employees handling hazardous medications, requiring safety programs that are comprehensive in nature, involving all relevant departments. Such a program is characterized by the presence of P&Ps that are consistent with national guidelines, the availability of education, training in safe HD handling, the provision of equipment and supplies, management engagement in and support for safety, and a medical surveillance process. Safe handling of HDs increases when pharmacists, nurses, and safety professionals work together to ensure safety for all staff handling these medications.

References

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Martha Polovich, PhD, RN, AOCN, is the director of clinical practice, nursing research and education at the Duke Oncology Network in Durham, North Carolina. Dr. Polovich has been an oncology nurse since 1980, having been responsible for chemotherapy administration in inpatient and outpatient settings. She is co-editor of the ONS Chemotherapy and Biotherapy Guidelines and Recommendations For Practice and editor of the ONS publication Safe Handling of Hazardous Drugs. She has been the ONS liaison to the NIOSH Hazardous Drug Safe Handling Working Group since 2000 and the ONS representative to the ASCO/ONS Chemotherapy Safety Standards steering committee since 2008.

SIDEBAR
Institute a Medical Surveillance Program
OSHA recommends that employers of health care workers who are involved in the direct handling of HDs have a medical surveillance program that monitors the health effects of these drugs on their employees. Medical surveillance involves the collection and interpretation of data for the purpose of detecting changes in the health status of working populations. Medical surveillance is not a method of primary prevention, but is a secondary prevention tool that provides a means of early detection of potential HD-related health problems, as well as a way to monitor the effectiveness of other tenets of a safe handling program. 

Implementing a medical surveillance program may seem to be challenging to organizations due to cost concerns, but this trepidation may be due to an inaccurate view of what such a program entails. Pharmacy leaders may believe surveillance is defined as an annual laboratory evaluation of all potentially HD-exposed employees, which is not necessarily a requirement. There are many cost-effective ways of providing employee monitoring. However, regardless of the method chosen, two aspects of medical surveillance must be provided: employers must be able to identify workers who are at risk for exposure based on their work responsibilities, and they must have a plan for follow-up after acute employee exposure, such as an accidental spill.

A minimum requirement of health care organizations is to be able to identify those employees who handle hazardous drugs. Ideally, employee health professionals should be responsible for maintaining a list of employees who may be exposed to HDs when performing their duties in order to identify which workers to observe for changes in health status. Many organizations already have programs in place for work-related exposures (eg, tuberculosis and hepatitis B), which require periodic contact or evaluation by employee health, and this program can be used as a template to follow during those periodic encounters, with a few modifications. For example, physical examination of the site of exposure should be performed as soon as possible. Blood specimens collected immediately after exposure are nearly as good as baseline lab values for comparison should health changes occur. Follow-up monitoring should be based on the drug half-life and/or expected nadir of blood counts, if applicable. 

Health changes from HD exposure can be identified by symptom complaints, physical findings, and laboratory values that deviate from the expected norms, and can be collected using a health appraisal questionnaire (see Table 1) on an annual basis. The questionnaire should assess both general health and reproductive health, focusing on systems most likely to be affected by HD exposure. Documented health changes should trigger a physical examination and laboratory testing based on the results. Laboratory testing need not be done on an annual basis for all employees, but may be done less frequently in the absence of identified health problems. Additional data may be collected along with health information, such as frequency of HD handling activities, how often PPE is used, and the occurrence of spills or known exposure since the last evaluation. These factors can be used in decision-making for follow up.
Acute employee HD exposure requires prompt intervention to minimize harm. For example:

• Employees must be able to access information about emergency measures and know the process for reporting 
• Employees should consult the material safety data for the involved drug to determine measures that are specific to the agent 
• If skin is exposed to an HD, the employee should remove contaminated clothing to minimize skin contact and wash the exposed area thoroughly with soap and water 
• For eye exposure, employees should flush the eye with water or saline solution for 15 minutes, followed by emergency evaluation 
• Inhalation exposure should be treated by going to an area where fresh air is available
• Following inadvertent ingestion of HDs, individuals should not induce vomiting unless directed to do so by the material safety data sheet
• All acute exposure should be documented in an incident or employee injury/exposure report, and employees should be evaluated by employee health

Post-exposure evaluation should be tailored to the type of exposure that occurred. Physical examination should focus on the exposed site, as well as the organ systems commonly affected by HDs, such as skin, mucous membranes, and the hematopoietic system. Treatment must be guided by emergency protocols and based on the employee’s signs and symptoms. The employee health professional is responsible for evaluating the need for specific laboratory work based on the known toxicity of the agent in question, or based on the material safety data sheet.