Safe Handling of Hazardous Drugs: Preparation & Administration

1. Safe Handling of Hazardous Drugs:Preparation & Administration

2. Consider the Risk • Increasing evidence of exposure • Increasing numbers of cancer patients • More drug combinations • Higher doses of drugs • More potent drugs • Increasing non-cancer use of antineoplastics • New treatment settings Source = Thomas Connor, Ph.D., NIOSH

3. Potential Routes of Exposure Inhalation Breathing contaminated air(aerosols and vapors) Dermal contact Touching contaminated surfaces Direct contact with drugs Ingestion Chewing gum Hand-to-mouth (eating and drinking)

4. Working with or near hazardous drugs in health care settings may cause skin rashes, infertility, miscarriage, birth defects, and possibly leukemia or other cancers. Warning! National Institute for OccupationalSafety and Health (NIOSH) Alert NIOSH Alert Publ. No. 2004-165; http://www.cdc.gov/niosh/docs/2004-165/

5. Toxicity of Antineoplastic Drugs • Long-Term Effects • Reproductive • Spontaneous abortions • Malformation of offspring • Low birth weight • Prolonged time to pregnancy • Developmental • Genetic • End organ damage • Cancer • Acute Effects • Irritation (skin, eyes) • Nausea • Vomiting • Headache • Dizziness • Hair loss • Mucosal sores • Organ damage (liver, kidney, bladder, lung) 5

6. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs Melissa A. McDiarmid, MD, MPH, Marc S. Oliver, MPH, MBA, RN, Tracy S. Roth, RN, BSN et al. Objective To determine the frequency of “signature” chromosomal abnormalities in oncology workers handling anticancer drugs. Source: Journal of Occupational and Environmental Medicine, Volume 52, no. 10, Pages 1028-1034

7. Results/Conclusion An excess of structural and total abnormalities of chromosome 5 was observed in the high-exposure group compared with the unexposed. Increased incidence rate ratios (IRRs) for abnormalities of chromosome 5 and for either chromosome 5 or 7 were obtained at 100 handling events. Effect sizes were augmented 2- to 4-fold when alkylating agent handling alone was considered. Biologically important exposure to genotoxic drugs is apparently occurring in oncology work settings despite reported use of safety practices.

8. Closed-System Drug Transfer Devices areRecommended to Prevent Hazardous Drug Exposure • NIOSH (2004) “Consider using devices such as closed-system transfer devices... closed systems limit the potential for generating aerosols and exposing workers…” • ONS (2005) “The PhaSeal System is the only documented closed system on the market. This system is designed to prevent leakage of drugs into the environment during preparation and administration” • ASHP (2006) “Consider using closed-system drug-transfer devices while compounding hazardous drugs…vented, filtered products are not closed”

9. Closed-System Drug Transfer Device (CSTD) “A drug transfer device that mechanically prohibits the transfer of environmental contamination into the system and the escape of hazardous drug or vapor concentrations outside the system.” Published in NIOSH Alert (DHHS [NIOSH] Publication Number 2004–165) on page 44.

10. Closed-System Drug Transfer Device (CSTD) Independent, peer-reviewed, published clinical research shows that – across both preparation and administration – PhaSeal is the only vial transfer device that meets the airtight and leakproof definition of a closed-system drug transfer device (CSTD).

11. Methodologies That Have Been Used to Determine if a Product Meets the NIOSH Definition of a CSTD • Surface contamination studies • Human uptake studies • Airtight studies (to determine containment of aerosols/vapors) • Leakproof studies (to determine containment of liquids) • pH test • Microbiological contamination studies

12. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents Catherine Wick, Matthew Slawson, James Jorgenson, Linda Tyler,Huntsman Cancer Institute, Salt Lake City, Utah Published in Am J Health Syst Pharm. 2003; 60: 2314-2320

13. Agent # positive samples* % Pre-PhaSealCyclophosphamide 18/48 38 Ifosfamide 10/47 21 Total Positive Urine Samples Post-PhaSeal Cyclophosphamide 0/49 0 Ifosfamide 0/49 0 • All 3 groups had positive urine samples Pre-PhaSeal • After using PhaSeal for 6 months, there were no positive urine samples recorded There is a direct correlation between surface contamination and human uptake. *Fraction represents the number of positive samples collected against the total amount of voids during the 24-hour urine collection time period

14. Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs James A. Jorgenson, RPh, MS, FASHP; Susan M. Spivey, RPh, DDS, PharmD; Cam Au, PharmD; David Canann, PharmD; Howard Ritter, PharmD;Bart Smith, Senior Pharmacy Intern The purpose of this study was to examine several commercially available systems or devices to ascertain which meet the NIOSH definition of closed-system drug transfer device (CSTD) and theISOPP definition of containment device (airtight and leakproof). Objective Source: Hospital Pharmacy Vol. 43, No. 9

15. Devices Tested • B. Braun OnGuard™ System (Teva Medical LTD) • Chemo Mini-Spike Plus™ Dispensing Pin (B. Braun Medical Inc.) • Alaris SmartSite® (Cardinal Health) • Chemoprotect® Spike (Codan US Corporation) • PhaSeal® (Carmel Pharma)

16. Smoke Study: Update The test was reproduced by the University of Utah using these additional devices: • Spiros™ and Clave® (ICU Medical) • Vial Adapter and Clave® (ICU Medical) • CyTwo-Fer (Baxa) • CHEMO-AIDE (Baxter) Results still showed that – across both preparation and administration – PhaSeal is the only vial transfer device that meets the airtight and leakproof definition of a closed-system drug transfer device (CSTD).

17. Devices Tested B. Braun OnGuard™ System (Teva Medical LTD) Chemo Mini-Spike Plus™ Dispensing Pin(B. Braun Medical Inc.) Alaris SmartSite®(Cardinal Health)

18. Devices Tested Chemoprotect® Spike (Codan US Corporation) PhaSeal®(Carmel Pharma)

19. Smoke Study: Update Spiros™ and Clave® (ICU Medical) Vial Adapter and Clave® (ICU Medical) CyTwo-Fer (Baxa) CHEMO-AIDE (Baxter)

20. Results Filter products, such as the Tevadaptor (OnGuard) system and the Alaris system, which rely on a 0.22-micron filter, did not retain the titanium particles and, therefore, could not meet the NIOSH definition of a CSTDand theISOPP definition of containment device. They were clearly not airtight or leakproof. These systems also showed visible leakage of fluorescein at the dry connections and, therefore, cannot be considered closed from this perspective either. Only the PhaSeal system met the NIOSH and ISOPP definitions of a CSTD/containment device.

21. Leakproof Connection Integrity Test for 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 leakproof or have the potential to allow drugs to escape into the environment during the preparation and administration phases of hazardous drug handling.

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

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

24. The PhaSeal System: The Definition of Closed

25. The Only Clinically Proven Closed-System Transfer Device • PhaSeal meets the NIOSH definition of a closed-system drug transfer device • Proven efficacious in more than 15 independent, peer-reviewed published studies • Noted by clinical thought leaders as ‘The Gold Standard’ in safe handling • Over 15 years of experience dedicated to the safe handling arena

26. Unique Features Airtight Expansion Chamber This sealed chamber contains aerosols and vapors while equalizing pressure in the vial during drug preparation. It allows you to see and know that it’s closed and you’re protected. Leakproof Double Membrane PhaSeal’s proven dry connections eliminate exposure when connecting and disconnecting from vials, syringes, IV bags and patient IV lines. And because each membrane is clinically proven to remain dry through multiple manipulations, you can safely conduct multiple-dose administrations using a single, designated port.

27. Unique Features Intuitive, Drug-Saving Design The Injector’s smart design enables you to retrieve all the drug from the vial while its ergonomic, passive safety technology allows you to work with ease and confidence. Just push-turn-push and you have a safe, leakproof connection (fig. 5). Universal Compatibility The PhaSeal System is universally compatible with your existing protocol to offer full-spectrum protection without hassle or compromise. During preparation, PhaSeal allows you to work with all drugs and standard drug vials – from the largest of multi-dose vials to the smallest 13mm-neck or <10mL vials – while its compatibility with all standard luer lock tubing, connections and ports means you’ll appreciate simple integration in administration, as well.

28. Clinical Training & Support

29. Clinical Training & Support • Dedicated certified clinical oncology staff for in-service training and ongoing support • Education materials to share with your staff such as instructional videos, instructional posters and more • Policies and procedures for various pharmacy and nursing hazardous drug applications • Online Continuing Education (CE) credits for pharmacists, nurses and risk managers available via www.phaseal.com

30. Drug Savings

31. With PhaSeal Injector

32. With Fixed Spike

33. Assessing Cost of a Device • Cost of implementing a device is equal to the cost of components plus cost of drug that is lost with its use (ICU Medical SpirosTM/Clave® and loss of 1.04ml)

34. Drug Vial Optimization (DVO) Drug Vial Optimization (DVO) Model Combining Safety and Savings For more than 14 years, the PhaSeal System has been the only clinically proven closed-system drug transfer device on the market. And now, the same System that has been uniquely proven to protect you and your employees from hazardous drug exposure can also help you realize an economic benefit. Here’s how it works. DVO Maintaining microbiological integrity creates cost savings Maintaining the microbiological integrity of the drug vial enables your facility to extend the use of the drug until the chemical expiration date. Drugs that might otherwise be discarded may instead be conserved. Application of this concept – as well as the purchase of the largest available vials – can result in cost savings for your facility

35. Economic Impact of the Preparation Scenario for Cytotoxic Drugs: An Observational Study Johan Vandenbroucke, PharmD; Hugo Robays, PharmD Objective To evaluate the financial impact of three different preparation and conservation scenarios for cytotoxic drugs. Source: European Journal of Hospital Pharmacy Practice, Volume 14, Pages 37-42

36. Method • Three simulation preparation/conservation scenarios: • Scenario One: Residual fraction of the drug was discarded • after each preparation • Scenario Two: Residual fraction of vial was used until the end • of the day • Scenario Three: Residual fraction of the vial was used until the • chemical/physical expiration date

37. Results On average, the overall cost of cytotoxic preparation can be decreased by 7% to 15% depending on the applied scenario.

38. Not All Transfer Devices are Created Equal • It is important to differentiate between available products on the market • Not all transfer devices are CSTDs • Choosing a CSTD should be based on peer-reviewed and published clinical evidence; not white papers and data on file

39. The Value of PhaSeal • ExperiencePhaSeal is supported by Carmel Pharma’s 15+ years of dedicated CSTD research and development. • QualityThe efficacy of PhaSeal is clinically proven and uniquely validated by more than 15 independent, peer-reviewed, published clinical studies. • Ease of Use PhaSeal’s passive safety technology and built-in locking mechanism makes the System easy to use. The Injector’s unique design allows you to retrieve all the drug from the vial for increased cost savings and waste optimization.

40. Summary • Consider the Evidence… • Hazardous drug exposure is a serious risk • Studies show a direct correlation between surface contamination and human uptake • NIOSH, ASHP, ONS, USP <797> and ISOPP all have similar recommendations for the safe handling of hazardous drugs —including use of a (airtight, leakproof) CSTD • Independent, peer-reviewed, published clinical studies confirm that PhaSeal prevents hazardous drug interaction and is the only device available that meets both the NIOSH and ISOPP definition of a CSTD

41. Questions ?

42. Thank You!