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Safe Handling of Hazardous Drugs:Preparation & Administration

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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

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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)

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National Institute for OccupationalSafety and Health (NIOSH) Alert

NIOSH Alert Publ. No. 2004-165; http://www.cdc.gov/niosh/docs/2004-165/

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!

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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)

Toxicity of Antineoplastic Drugs

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Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs

ObjectiveTo determine the frequency of “signature” chromosomal abnormalities in oncology workers handling anticancer drugs.

Melissa A. McDiarmid, MD, MPH, Marc S. Oliver, MPH, MBA, RN, Tracy S. Roth, RN, BSN et al.

Source: Journal of Occupational and Environmental Medicine, Volume 52, no. 10, Pages 1028-1034

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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.

Results/Conclusion

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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”

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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.

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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).

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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

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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

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Pre-PhaSeal Cyclophosphamide 18/48 38

Ifosfamide 10/47 21

Post-PhaSeal Cyclophosphamide 0/49 0

Ifosfamide 0/49 0

*Fraction represents the number of positive samples collected against the total amount of voids during the 24-hour urine collection time period

• 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.

Total Positive Urine Samples

Agent # positive samples* %

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Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs

Objective

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

Source: Hospital Pharmacy Vol. 43, No. 9

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 the ISOPP definition of containment device (airtight and leakproof).

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• 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)

Devices Tested

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• 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).

The test was reproduced by the University of Utah using these additional devices:

Smoke Study: Update

B. Braun OnGuard™ System (Teva Medical LTD)

Chemo Mini-Spike Plus™ Dispensing Pin(B. Braun Medical Inc.)

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Devices Tested

Alaris SmartSite®

(Cardinal Health)

Chemoprotect® Spike(Codan US Corporation)

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Devices Tested

PhaSeal®(Carmel Pharma)

Spiros™ and Clave® (ICU Medical)

Vial Adapter and Clave® (ICU Medical)

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Smoke Study: Update

CyTwo-Fer(Baxa)

CHEMO-AIDE(Baxter)

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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 NIOSHdefinition of a CSTD and the ISOPP 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.

Results

Leakproof Connection Integrity Test for Devices Intended for Handling Hazardous Drugs

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.

James A. Jorgenson, RPh, MS, FASHP, Director of PharmacyUniversity of Utah Health Care, Salt Lake City, Utah

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Clave® Vial Adaptor& Spiros™ Male Connector(ICU Medical, Inc.)

B. Braun/Tevadaptor™Vial Adaptor & Syringe Adaptor (Teva Medical Ltd.)

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Alaris SmartSite® Vented VialAccess Device & Texium™ Male Luer (Cardinal Health)

PhaSeal® Protector& Injector Luer Lock(Carmel Pharma, Inc.)

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The PhaSeal System: The Definition of Closed

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• 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

The Only Clinically Proven Closed-System Transfer Device

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Unique Features

Airtight Expansion ChamberThis 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 MembranePhaSeal’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.

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Unique Features

Intuitive, Drug-Saving DesignThe 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 CompatibilityThe 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.

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Clinical Training & Support

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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

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Drug Savings

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With PhaSeal Injector

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With Fixed Spike

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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)

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Drug Vial Optimization (DVO)

Drug Vial Optimization (DVO) ModelCombining Safety and SavingsFor 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 savingsMaintaining 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

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Economic Impact of the Preparation Scenario for Cytotoxic Drugs: An Observational Study

Objective

To evaluate the financial impact of three different preparation and conservation scenarios for cytotoxic drugs.

Johan Vandenbroucke, PharmD; Hugo Robays, PharmD

Source: European Journal of Hospital Pharmacy Practice, Volume 14, Pages 37-42

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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

On average, the overall cost of cytotoxic preparation can be

decreased by 7% to 15% depending on the applied scenario.

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Results

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• 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

Not All Transfer Devices are Created Equal

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.

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• 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

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Summary

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Questions ?

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Thank You!