Q&A with Colleen A. Moody, PharmD Candidate; 
Lindsey B. Poppe, PharmD, MS, BCPS; and 
Stephen F. Eckel, PharmD, MHA, BCPS, FAPhA, FASHP, FCCP  

Pharmacy Purchasing & Products: What exposure risks exist during hazardous drug preparation and administration? 
UNC Hospitals: Hazardous drugs, including chemotherapy, pose exposure risks at several points throughout the medication-use process. During preparation, risk occurs when reconstituting lyophilized drugs, spiking vials, transferring the drug to IV bags and syringes, and cleaning drug preparation areas. Exposure can occur through aerosolization of the drug and external contamination of the medication vial. In addition, exposure may occur when IV lines are primed and syringes are connected or disconnected from injection ports; this is especially true if a closed system transfer device (CSTD) is not used to prevent droplet formation. 

There are additional—perhaps less obvious—areas in the medication-use process where exposure could occur. Hospitals must fully assess the possibility for hazardous drug exposure in all areas hazardous drugs are used, including:

• Medication handling and storage. Consider every area where potential hazardous drug exposure could occur, from the moment hazardous medications enter the hospital until the final disposal of hazardous drug waste. Staff involved in transporting and handling these medications should be protected from exposure just as employees preparing and administering these medications are protected. 
• Hospital areas where compounding staff congregate. If strict garbing requirements are not followed, staff involved in compounding hazardous medications can transfer hazardous drug residue from the admixture area to other locations in the hospital. This could lead to exposure beyond those staff working in the preparation area. Enforcing a strict personal protective equipment (PPE) policy minimizes the likelihood of transferring surface contamination from the compounding area to other hospital locations. 
• Non-compounding areas that receive airflow from the compounding area. While a hospital’s main compounding area typically vents directly outside, some clinics or other hazardous drug compounding areas might have engineering controls with insufficient venting. For example, if a biological safety cabinet (BSC) is located where the air ducts connect with another area of the building, this could lead to aerosolization and exposure risks in that area receiving the airflow. Hospitals can determine the airflow from the BSC with their plant engineering department and develop a plan to externally exhaust the BSC. 

PP&P: What is the best approach for developing safe handling policies and procedures (P&Ps) for hazardous drugs that cover all employees? 
UNC Hospitals: Input from a multidisciplinary team is vital to develop safe handling P&Ps. Participation from receiving, pharmacy, nursing, and environmental services will ensure that the recommendations are comprehensive enough to protect all employees, and engaging staff in the process ensures that all departments buy-in to the process. 

A multidisciplinary approach was utilized to implement several P&Ps at the UNC Cancer Hospital Infusion/Inpatient Pharmacy (CHIP) to reduce exposure risk and create safe handling practices. Elements of these P&Ps include:

• Hazardous compounded sterile preparations must be prepared within an ISO Class 5 BSC, using a CSTD when possible. In fact, CSTD use is required during preparation and administration of approximately 99% of hazardous drugs (only intrathecal preparations or drugs packaged in ampules are excepted). 
• Material Safety Data Sheets for all hazardous drugs used in the hospital are immediately accessible at all times to hospital personnel. 
• Pharmacy personnel must wear PPE rated for chemotherapy in the cleanroom. 
• A hazardous and chemotherapeutic drug compendium is actively maintained that identifies appropriate and safe procedures, with specific instructions for reconstituting, admixing, packaging, and labeling each drug. 
• Although chemotherapy spills within the hood are rare, plastic-backed absorbent chemotherapy mats are used within the BSC as a precautionary measure. 
• Technicians are trained to remove all unnecessary equipment from their work space and perform compounding tasks in a precise, deliberate, and algorithmic manner during the preparation of hazardous drugs. 
• Oral oncolytics are packaged in single-dose units within a BSC to minimize exposure to non–oncology trained personnel. 
• All hazardous drugs are hand-delivered to the unit in sealed plastic bags labeled as hazardous materials. 
• Nurses administering hazardous drugs must garb in a chemoprotective gown and wear two pairs of chemotherapy rated gloves—an inner pair under the sleeves and an outer pair over the cuffs of the gown. (See TABLE 1 for UNC Hospitals’ PPE Guidelines.)
• When administering a hazardous drug via inhalation, an N95 respirator must be worn. 
• If drug exposure to the face is possible (ie, administering drugs via gastric tube), face shields must be worn. 
• Hospital personnel responsible for cleaning the facilities used by patients receiving hazardous drugs are required to follow hazardous drug precautionary measures, including the use of gloves and disposal policies set forth by the environmental health and safety department. 
• New drugs added to the formulary are evaluated by the P&T committee to determine whether they should be classified as hazardous; six to 12 months later a medication-use evaluation is conducted to determine appropriate use. 
• All BSCs are certified every six months and surface contamination wipe tests are performed routinely to ensure a contamination-free environment.

Click here to view a larger version of this Table

These practices are included in a hospital-wide policy developed in collaboration with pharmacy, nursing, physicians, environmental services, and environmental health and safety. The chemotherapy policy is reviewed semi-annually at the oncology pharmacy and therapeutics (P&T) subcommittee, which is composed of representatives from these departments. 

PP&P: What staff training and monitoring is required to ensure safe use of hazardous drugs? 
UNC Hospitals: As part of our safe handling P&P, personnel working directly with hazardous drugs must complete formal training. Pharmacy technicians responsible for the preparation of hazardous drugs complete a six- to eight-week training program, which includes computer-based modules (purchased from a vendor), practical hands-on experience, and competency assessments (developed in-house). Computer-based modules cover aseptic technique, cleaning and disinfecting procedures, personnel garbing techniques, hazardous drug handling, waste disposal (see TABLE 2 for UNC Hospitals’ Pharmaceutical Waste Disposal Guidance Grid), and cleanup procedures. The hands-on portion of the training program teaches preparation practices within a BSC, including cleaning procedures, proper use of CSTDs, and preparing various chemotherapy and hazardous admixtures. Upon completion of both computer-based and practical training, the technician must demonstrate competency in all of these tasks through a written and a practical exam using media-fill challenge kits. 

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CHIP technicians complete both baseline and annual competencies. Once training is complete and competency is established, each technician’s aseptic technique is tested annually using media-fill challenge tests, as mandated by USP <797>. Pharmacists also complete robust training followed by a competency exam; a new exam is created each year, which pharmacists complete prior to their annual evaluation (see SIDEBAR 1). 

PP&P: How should practice challenges be identified?
UNC Hospitals: Areas needing improvement are assessed in various ways. Review of staff-reported near miss errors in which they intervened, regular communication with employees within the pharmacy, and continual vigilance to identify issues brought forward by nursing, medical staff, and hospital administrators can assist pharmacy in addressing areas of concern to ensure safety and improve services. 

UNC Hospitals recently completed a review of its medication preparation activities with the goal of reducing the time required to safely prepare a medication. Because extended wait times in the infusion clinic are consistently associated with dissatisfied patients, CHIP undertook a Lean Six Sigma Kaizen event in June 2013 to improve the turnaround times of medication preparation while maintaining safety. Participants included CHIP pharmacy staff, non-oncology pharmacists, oncology nursing, quality and business analysts, oncology leadership, and an infusion patient. Experimental trials were performed to identify areas where operational changes could be made to improve effectiveness, efficiency, and safety. The top three challenges identified by the Kaizen included: 

• We require two independent checks of the paper order: one by a pharmacist outside the cleanroom prior to compounding the order, and the second inside the cleanroom after the product was compounded. Because the second check occurred at the end of the process, any errors identified at this point caused the final product to be wasted and the process to restart.
• Multiple technicians were compounding orders but only one pharmacist was checking these orders; thus, a backlog of products waiting for the second check was not uncommon.
• Technicians prepared every drug in a given patient’s regimen at once instead of preparing one drug at a time, which created a higher possibility of error.

These challenges were resolved by shifting the responsibility for the second independent check (of the chemotherapy order, and then of the order against the label) to an additional pharmacist outside the cleanroom before preparation of the final product inside the cleanroom. Thus, the order was checked by two pharmacists outside the cleanroon prior to being prepared, thereby reducing waste and allowing the cleanroom pharmacist to focus on verification of the final product only. The double check by two pharmacists outside the cleanroom also eliminated the backlog of products waiting for a second check by allowing the inside pharmacist to focus on checking the prepared product against the label. In addition, we implemented a more intuitive technician workflow, wherein each technician prepares only one drug in a regimen at a time, even if a patient has a multidrug regimen. 

These improvements have resulted in a 57% reduction in turnaround time from baseline measurements taken 19 months ago, to an average turnaround time of 26 minutes. 

PP&P: How can pharmacy and nursing staff work together to mitigate exposure risk?
UNC Hospitals: The most successful way to mitigate risk is to foster an environment of open communication, collaboration, and trust between pharmacy and nursing personnel. A safe environment for employees and patients results when both departments put patients’ and the hospital’s needs above the interests of individual departments. At UNC, an oncology safety committee, comprised of representatives from pharmacy, nursing, and physicians, meets monthly to identify and resolve safety and practice concerns. Medication variance reports are reviewed and discussed non-punitively to identify system solutions; these reports also help identify and resolve potential workarounds in the system. When policies need to be updated, the safety committee makes recommendations to the oncology P&T subcommittee for approval; once approved, staff is educated about the changes before implementation.

Cooperation between pharmacy and nursing improves safety and workflow for both departments. For example, collaborating with nursing colleagues during our recent implementation of the electronic medication administration record (eMAR) presented opportunities to streamline pharmacist order entry of chemotherapy. We identified that variation in the way pharmacy entered an order—while acceptable in the pharmacy system—translated differently to nursing. One-time-only orders can be entered two ways into the pharmacy system: the first allows the nurse to administer a medication when they are ready to start a new drug, and the order stays on the eMAR for 24 hours; the second option limits nurses to give the dose at the specific time assigned by pharmacy. Working together with nursing, we identified the safest and most efficient way to enter and administer the order, and standardized that method consistently. The approach decided upon depends on the preparation. For first doses in a regimen given only one time (eg, rituximab), the order stays on the eMAR for 24 hours (the first option). If the patient is receiving an intrathecal medication that is only going to be given on day five of the regimen, the second option is chosen.  

While practice change is best instilled through multidisciplinary efforts, pharmacists are nonetheless responsible for maintaining oversight of the entire medication-use process, including drug administration. Pharmacists’ comprehensive understanding of the medication-use process positions us to lead the effort in implementing safe practices. 

PP&P: How should a plan be developed for medical surveillance of personnel handling hazardous drugs?
UNC Hospitals: When considering a medical surveillance plan, pharmacy must decide what method best corresponds with the needs of the hospital: routine- or incident-based medical surveillance. Incident-based surveillance is prompted only when hospital personnel are inappropriately exposed to a hazardous drug, most commonly from an accidental spill. Exposed personnel are monitored by the hospital’s epidemiology department or designee from the time of the incident forward. In order to be successful with this approach, personnel must undergo training and competency testing prior to preparing and handling hazardous drugs without direct training supervision. They also need to be diligent in reporting exposures. A benefit of incident-based medical surveillance is that it minimizes expense and employee burden. Routine surveillance occurs on a scheduled basis, usually annually, and includes laboratory and provider appointments for testing. This is a proactive approach, but increases testing expense and labor hours. No data exists to support one surveillance method over the other, but either routine- or incident-based medical surveillance should occur. Our organization currently uses the incident-based approach for medical surveillance, as this was determined to be the most optimal method for our employees. (See SIDEBAR 2. NIOSH’s Components of a Medical Surveillance Program.)

An additional recommendation is to monitor routine surface sampling results for hazardous drugs. While technically not considered medical surveillance, surface monitoring can be used as a marker to determine potential hazardous drug exposure risk for employees. Should repeated tests document elevated levels of contamination, practice and education improvements are required to reduce employee exposure risk.

Colleen A. Moody is a second-year PharmD candidate at the University of North Carolina (UNC) Eshelman School of Pharmacy, a pharmacy intern at UNC Hospitals North Carolina Cancer Hospital, and a student member of the American Society of Health-System Pharmacists (ASHP). 

Lindsey B. Poppe, PharmD, MS, BCPS, is clinical manager for the oncology service line and infusion services at UNC Hospitals. She received her PharmD from the University of Wyoming and completed a two-year combined Health-System Pharmacy Administration residency and Masters degree from UNC Hospitals and UNC Eshelman School of Pharmacy. Lindsey is actively involved in ASHP and the Hematology/Oncology Pharmacy Association.

Stephen F. Eckel, PharmD, MHA, BCPS, FAPhA, FASHP, FCCP, is an associate director of pharmacy at UNC Hospitals, as well as a clinical associate professor in the division of practice advancement and clinical education and the division’s vice chair for graduate and postgraduate education. In addition, he is director of graduate studies and is in charge of the two-year master of science in pharmaceutical sciences with a specialization in health-system pharmacy administration. Stephen received both his BS and PharmD from the UNC Eshelman School of Pharmacy and received his MHA from the UNC Gillings School of Global Public Health.

SIDEBAR 1
Sample Questions from UNC Hospitals’ Yearly Pharmacy Oncology Competency Exam
DG is a 60-year-old male diagnosed with a squamous cell carcinoma of the oropharynx. He presents for his first cycle of chemotherapy using cisplatin 100 mg/m2 IV once over one hour on day one. 

1. Which of the following must be present on the chemotherapy order for DG before it can be executed (choose 4)?  

1. The calculated amount of chemotherapy, either ordered as “per day” or “per dose” 
2. The brand name of the medication being ordered  
3.  The complete text of the active research protocol being used  
4.  The patient’s known allergies 
5. The patient’s date of birth 

2. DG’s liver panel reveals a total bilirubin >5 and an AST of 175. What dose adjustment of the cisplatin must be made? 

1. No adjustment is required 
2. Only 75% of the calculated dose should be given 
3. Only 50% of the calculated dose should be given 
4. The original dose should be administered, but over a two-hour interval  
5.  More information is needed 

3. Which prophylactic antiemetic regimen should be given to DG on day one of his first cycle of chemotherapy? 

1. Lorazepam 0.5-1 mg PO/IV 
2. Ondansetron 24 mg PO or 8 mg IV plus dexamethasone 12 mg PO/IV aprepitant 125 mg PO 
3. Prochlorperazine 10-25 mg PO or PR q 6-12 h or metoclopramide 0.5 mg/kg PO q 6 h 
4. Dexamethasone 4-8 mg PO q 8-12 h plus or minus prochlorperazine 10-25 mg PO or PR q 6-12 h 
5. Ondansetron 24 mg PO or 8 mg IV plus dronabinol 5-15 mg/m2 PO q 3-6 h 

4. Which of the following toxicities is cisplatin most likely to cause? 

1. Myelosuppression 
2. Hypersensitivity/rash 
3. Alopecia  
4.  Hepatotoxicity 
5. Electrolyte wasting (hypokalemia and hypomagnesemia) 

5. The nurse administering DG’s medications calls the pharmacy asking about the antidote (isotonic sodium thiosulfate) for cisplatin if extravasation were to occur. Which of the following statements is false? 

1. If 10% sodium thiosulfate is used, prepare 2 mL for every 100 mL of cisplatin 
2. The antidote should be injected intramuscularly 
3. Vesicant protection is required only if more than 20 mL of 0.5 mg/mL extravasates 
4. The antidote should be prepared as a 1/6 molar solution 
5. The antidote should be prepared using sterile water for injection 

6. Which of the following agents requires REMS enrollment by the patient, prescriber, and the pharmacy? 

1. Suboxone 
2. Lotronex 
3. Aranesp 
4. Ventavis 
5. Iressa

The sample exam is available in its entirety at www.pppmag.com/onccompexam

SIDEBAR 2 
NIOSH’s Components of a Medical Surveillance Program*
Elements of a medical surveillance program for workers exposed to (ie, handle as a part of their work duties) hazardous drugs should include the following:

• Reproductive and general health questionnaires completed at the time of hire and periodically thereafter. Unless information about relevant symptoms and medical events such as spontaneous abortions is deliberately sought, their occurrence is likely to go unreported. Opportunities to identify patterns of occurrence implying defects in engineering controls, technique, or other preventive measures may be similarly missed
• History of drug handling as an estimate of prior and current exposure, including dates of duty assignment related to hazardous drugs and similar types of information
• A plan to provide initial baseline clinical evaluation, including appropriately targeted medical history, physical examination, and laboratory testing for workers identified as being potentially exposed to hazardous drugs that anticipates their potential toxicities
• A follow-up plan as needed for workers who have shown health changes suggesting toxicity or who have experienced an acute exposure (substantial skin contact or inhalation exposure, cleaning a large spill [a broken IV bag, leaking IV line], etc)

*Medical Surveillance for Health Care Workers Exposed to Hazardous Drugs. Workplace solutions from the National Institute for Occupational Safety and Health.http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/pdfs/2007-117.pdfAccessed November 14, 2013.