Proper Handling of Hazardous Drugs: Topics for Oncology Nursing

1. Proper Handling of Hazardous Drugs: Topics for Oncology Nursing Presented by Kerry Mahar, RN, MSN, AOCN Dana Farber Cancer Institute Norwell, MA

2. Disclosure • Kerry Mahar serves as an Advisory Board member for Carmel Pharma. • This program has been supported by an unrestricted educational grant provided by Carmel Pharma. • This program is intended strictly for educational purposes and does not constitute as an endorsement of any product or off-label usage.

3. CPE Program Information ANCC Program CNE #: O-AO-12716-04-08 1.5 Contact Hours Expires: April 21, 2010 • Questions:STAT Educational Servicesphone 888-247-8700fax 888-247-8706

4. Program Learning Objectives At the completion of this program, participants should be able to: • Describe the potential health risks of handling hazardous drugs in oncology nursing practice. • Identify the appropriate PPE needed for safe handling of hazardous drugs. • Review current recommendations and guidelines for safe handling of hazardous drugs. • List recommended practices for the safe handling of hazardous drugs during drug administration and disposal of drugs. • List recommendations for medical surveillance for nurses who handle hazardous drugs. • Describe essential elements of staff education/training related to safe handling of hazardous drugs.

5. Exposure Opportunity is Increasing • WHO estimates a 50% increase in cancer patients in the next 20 years • Use of drugs for non-malignant disease (RA, SLE) • Anti-viral agents for HIV treatment and other viral illnesses • Investigational (IND) Drug Development/Clinical Trials

6. Definition of Hazardous Drugs • Carcinogenic • Teratogenic • Reproductive toxicity • Organ toxicity at low doses • Genotoxic • Structure or toxicity similar to drugs classified as hazardous (NIOSH, 2004)

7. End Organ Damage • By definition a drug is deemed hazardous if it causes harm to organs • Liver damage was reported in the literature on three nurses (working 6, 8 and 16 years) with chemotherapeutic agents • Cardiotoxicity related to the use of anthracyclines Source: Sotaniemi EA, Sutinen S, Arranto AJ et al. Liver damage in nurses handling cytostatic agents. Acta Med Scand. 1983; 214:181-9.

8. Cancer Risk in Workers • Leukemia in nurses (Skov et al, 1992)(RR = 10.65) • Cyclophosphamide (Sessink et al, 1993)(1.4-10 excess cases/million) • NHL & skin cancer (Hansen & Olsen, 1994) (SIR = 3.7) • Overall increased cancer risk(Martin, 2005)(OR = 3.27) RR = Relative Risk; SIR = Standardized Incidence Rate; OR = Odds Ratio

9. Reproductive Risks in Workers • Fetal abnormalities (Hemminki et al, 1985) • Spontaneous Abortions (Stucker, 1990) • Infertility (Valanis et al, 1997) • Miscarriages (Valanis et al, 1999) • Infertility, premature labor, low-birth weight, learning disabilities in offspring (Martin, 2005) • Infertility (Fransman, 2007)

10. Occupational Exposure to Antineoplastic Agents • Kaiser Permanente Center for Health Research • 7,094 pregnancies of 2,976 pharmacy and nursing staff studied • Exposure of mother to handling antineoplastic agents during pregnancy was associated with a significant increased risk for spontaneous abortion and stillbirth • Increased risk for miscarriages by 40 - 50% • Increased risk for low birth weight by 17-fold • Increased risk for congenital malformations by 5-fold Source: Journal of Occupational & Environmental Med Vol.41; 8: 632-638

11. Teratogenicity • Conflicting opinion on exposure during 2nd and 3rd trimesters • Greatest danger during 1st trimester • Hemminki case control study of Finish oncology nurses actively handling chemotherapy during 1st trimester • Demonstrated statistically significant increase in risk for malformations • Odds ratio of 4.7 (p=0.02) Source: Hemminki K, Kyyronen P, Lindbohm ML. J Epidemiol Community Hlth 1985

12. Dermal* Direct contact Contaminated surfaces Ingestion Food, gum Hand-to-mouth Inhalation Aerosols Vapors Injection Sharps Breakage Modes of Contact for Drug Exposure to Healthcare Worker *Most common source of exposure (NIOSH, 2004)

13. Evidence of Exposure • Positive florescent scans (Valanis, 1998) • Positive urine tests for drug exposure • 18 Published studies • 16 detected drugs in urine • In 4 studies, drugs were found in the urine of workers with no direct HD contact • Contaminated vials - 12 studies since 1992 • Surface contamination - 14 studies since 1994

14. Drug Reconstitution With Needle & Syringe

15. Drug Transfer With Needle & Syringe

16. Transfer of Contamination from IV Bag Photographs courtesy of L. Hampton, RN, MS, FNP; Donayre Cancer Center, Whiteville, NC. Reproduced with permission.

17. Chemotherapy on Plastic-Backed Pad Photograph courtesy of L. Hampton, RN, MS, FNP; Donayre Cancer Center, Whiteville, NC. Reproduced with permission.

18. Where Else? Photographs courtesy of L. Hampton, RN, MS, FNP; Donayre Cancer Center, Whiteville, NC. Reproduced with permission.

19. On the Floor… Photograph courtesy of Libby Hampton, RN, MS, FNP; Donayre Cancer Center, Whiteville, NC. Reproduced with permission.

20. Thomas H. Connor, Roger W. Anderson, Paul J. M. Sessink, Larry Broadfield, Luci A. Power Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States Objective: This study was designed to demonstrate the presence of ctyotoxic drugs in the workplace. Source: AJHP 1999. 56:1427-32.

21. Evaluation of Surface Contamination Study was conducted at six cancer treatment centers • 3 in the United States and 3 Canadian centers • Wipe samples analyzed for • Cyclophosphamide and ifosfamide by GC-MS-MS • Fluorouracil by reverse-phase HPLC with UV-light detection • All pharmacies used class II Biological Safety Cabinets (BSCs) Source: AJHP 1999. 56:1427-32.

22. Evaluation of Surface Contamination • Measurable levels of antineoplastic agents were detected in • 75% of the pharmacy samples • Top area of BSC airfoil • Floor in prep room and in front of BSC • Work surface inside BSC • 65% of the administration samples • Floor around chair and patient bed • Top of preparation area Source: AJHSP 1999. 56:1427-32.

23. Personal Protective Equipment to Prevent Exposure in Healthhcare Workers • Gloves: tested with hazardous drugs, powder-free, latex, nitrile, neoprene • Double gloves • 30-min wear time • Gowns: tested with hazardous drugs, disposable, single-use, cuffs, back closure • Eye protection: • when splashing is possible • Respirator/mask: • for aerosols & spill clean-up • Close System Transfer Device (CSTD)

24. Catherine Wick, Matthew Slawson, James Jorgenson, Linda Tyler,Huntsman Cancer Institute, Salt Lake City, Utah Using a closed-system protective device toreduce personnel exposure to antineoplastic agents This study examined pharmacists, technicians and nurses at the Huntsman Cancer Center in Salt Lake City, Utah. Urine samples were collected separately from each group over a 24-hour time period. Source: Wick C. AJHP 2003; 60 (15): 2314-2320

25. Agent # positive samples* % Pre-PhaSealCyclophosphamide 18/48 38 Ifosfamide 10/47 21 Post-PhaSeal Cyclophosphamide 0/49 0 Ifosfamide 0/49 0 Total Positive Urine Samples • All 3 groups, pharmacists, pharmacy technicians and nurses had positive urine samples Pre-PhaSeal. • All locations were contaminated with 100% of RN’s and RPh’s contaminated and 30% of Pharmacy technicians • After using PhaSeal for 6 months, there were no positive urine samples recorded and surface level contamination was reduced 10X. • Source: Wick C. AJHP 2003; 60 (15): 2314-2320

26. Susan Spivey, RPh, DDS, PharmD, Pharmacy ManagerJames A. Jorgenson, RPh, MS, FASHP, Director of Pharmacy University of Texas, MD Anderson Cancer Center and University of Utah Health Care, Salt Lake City, Utah Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs Objective Fluorescein, a fluorescent indicator, was used to determine if the Tevadaptor™ System, Alaris System or PhaSeal System have the potential to allow drugs to escape into the environment during the preparation and administration phases of hazardous drug handling. Presented at ONS Congress, April, 2007, Las Vegas, NV.

27. Utah & MD Anderson StudyAre Connections Really Dry? • Evaluated dry connection of three commercially available systems for chemotherapy preparation • Utilized flourescein dye and transferred from a vial to syringe • Photographed vial and syringe adaptors under UV light • “Tapped” syringe adaptor on gauze to determine any leakage

28. PhaSeal® Protector, Injector Luer Lock &Y-site Connector by Carmel Pharma

29. Alaris Smartsite® & Texium by Cardinal Health

30. B. Braun OnGuard™Vial Adaptor, Syringe Adaptor & Luer Lock Adaptorby Teva Medical Ltd.

31. Results • With the PhaSeal System, no leakage was observed during any of the preparation or administration manipulations. • Both the Tevadaptor™ System and the Cardinal Health/Alaris System showed visible fluorescein leaks on the outside of each component during all manipulations of drug preparation and administration.

32. Leakproof Connection Integrity TestFor Devices Intended for Handling Hazardous Drugs James A. Jorgenson, RPh, MS, FASHP, Director of Pharmacy University of Utah Health Care, Salt Lake City, Utah Objective To determine if the ICU Medical System,B. Braun/Tevadaptor™ System, Cardinal/Alaris System or PhaSeal® System connections are leak proof or have the potential to allow drugs to escape into the environment during the preparation and administration phases of hazardous drug handling.

33. Methods • A liquid with low pH was used as a substitute for active drug. Litmus paper was used as pH indicator. Blue litmus paper turns red under acidic conditions. • Syringes were filled with fluid and injected into vials attached to the above transfer devices. After aspirating back and disconnecting, the connections of each device were pressed against litmus paper to detect the presence of any fluid. • Every component of each device was tested for 10 manipulations.

34. Clave® Vial Adaptor& Spiros™ Male Connector (ICU Medical, Inc.) B. Braun OnGuard™Vial Adaptor & Syringe Adaptor(Teva Medical Ltd.)

35. Alaris SmartSite® Vented VialAccess Device & Texium™ Male Luer (Cardinal Health) PhaSeal® Protector& Injector Luer Lock (Carmel Pharma, Inc.)

36. Visible leakage occurred outside of the components on theICU Medical System Clave® and Spiros™ connections,the B. Braun/Tevadaptor™ System and theCardinal Health/Alaris System during all manipulations. No leakage was observed in any of the manipulations with the PhaSeal® System. Results

37. Source: OSHA Technical Manual: Controlling Occupational Exposure to Hazardous Drugs US Department of Labor 1999 “Workers who are potentially exposed to chemical hazards should be monitored in systematic program of medical surveillance to prevent occupational injury and disease… The purpose of surveillance is to identify the earliest reversible biological effects so that exposure can be reduced or eliminated before the employee sustains irreversible damage” Medical Surveillance

38. Medical Surveillance For Who & Why… • To develop a standard that applies to all employees that support patient care services • Product preparation • Product administration & infusion • Acquisition transportation • Environmental service/housekeeping • Waste disposal • To identify biologic effects in anticipation that exposure will be reduced or eliminated [before an employee sustains irreversible damage or injury]

39. Medical Surveillance • NIOSH recommends (not a mandate) workers handling hazardous drugs be monitored • Medical history • Exposure history • Physical examination • Selected lab tests (complete blood count, reticulocyte count, or occult blood in urine) Source: NIOSH 117 document April 2007;www.cdc.gov/niosh/docs/wp-solutions/2007-117/NIOSH

40. Medical Surveillance Elements of a medical surveillance program • Reproductive and health questionnaires at hire and periodically • Laboratory work • Complete blood count, Urinalysis, Reticulocyte count, Transaminases (AST, ALT), Alkaline Phosphatase • Physical examination at hire and thereafter for abnormal findings on health questionnaire • Follow-up for those workers who have health changes or significant exposures • Tracking trends with questionnaires and sick-call

41. Medical Surveillance • NIOSH also suggests environmental sampling and/or biological monitoring when exposure is suspected • Some organizations considering urine testing for presence of chemotherapeutic agents

42. Environmental Monitoring(Wipe Testing) Measures the presence/release of the drug in the environment No information about uptake of the drug in the body of the worker No information about health-risk for the worker Biological Monitoring(Urine Testing) Assessment of uptake of the drug in the body of the worker Estimation of health-risk for the worker Environmental and Biological Monitoring

43. USP 797 Recommendation for Environmental Sampling • Suggests routine environmental sampling to detect uncontained hazardous drugs • Initial benchmark and every 6 months or more as needed • Surface wipe sampling of BSC or CACI and adjacent areas including the floor directly under the work area, counter tops, and patient care areas • Common marker drugs include cyclophosphamide, ifosfamide, methotrexate, and fluorouracil

44. USP 797 Recommendation for Environmental Sampling • If any measurable contamination is found, practitioners shall make the decision to identify, document and contain the cause • Action may include retraining, thorough cleaning, and improving engineering controls • USP notes that cyclophosphamide levels greater than1.0 ng/cm2 has been found to cause human uptake

45. Sessink Stride Risk Level Model • Based on predictive model for additional cancer cases per million workers based on cyclophosphamide urine levels • Stride risk level is 1 extra cancer case a year per million workers • Prohibitory risk level is 100 extra cancer cases a year per million workers Source: Dr. Paul Sessink Exposure Control; 2008

46. Sessink Model

47. Training on Handling of Hazardous Medications • ASHP (1990) and OSHA (1995) agencies must have a system for validating staff performance, and this must be documented • USP 797 revisions state all personnel who compound hazardous drugs shall be fully trained in the storage, handling and disposal of these drugs • Training must occur prior to preparing or handling hazardous CSPs & effectiveness must be verified by testing specific hazardous preparation techniques at least annually with results documented • Current MSDSs must be readily available in the areas hazardous drug preparation and administration Source: ASHP;Gullo, 1988:OSHA, 1990, 1995: USP 797 revisions (2007)

48. Training on Handling of Hazardous Medications Training must include at least: • Use of engineering controls including correct use of closed-system transfer devices • Use of PPE • Drug preparation • Drug Transport • Drug administration • Disposal of hazardous materials • Management of hazardous drug spills • Management of acute exposure

49. Training on Handling of Hazardous Medications Education Plan • Orientation to hazardous chemicals • Key contacts within the organization • Location of policies • Encourage employees to notify their physician of their possible occupational exposure to hazardous drugs • Educate employees of signs and symptoms • Based on the agents • Acute vs. chronic • Annual review of critical process and hazardous chemicals • Plan in place to educate on new chemicals

50. Training on Handling of Hazardous Medications Storage and Compounding • Evaluation of work environment and equipment • Policy & Procedures • Delineation of hazardous materials • Develop list with Safety departments • Labeling, storage, personnel issues, spill control • Education, preparation, administration, disposal • Evaluation of workspace • Ventilated cabinets • Use of equipment or devices to minimize exposure • Personal Protective Equipment (PPE) • Closed-system drug transfer device (CSTD) Source: Massoomi, 2007