Safe Handling of Hazardous Drugs:
Preparation & Administration
1
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
2
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)
3
National Institute for Occupational
Safety and Health (NIOSH) Alert
Warning!
Working with or near hazardous drugs in health care settings
may cause skin rashes, infertility, miscarriage, birth defects,
and possibly leukemia or other cancers.
NIOSH Alert Publ. No. 2004-165; http://www.cdc.gov/niosh/docs/2004-165/
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Toxicity of Antineoplastic Drugs
Acute Effects
• Irritation (skin, eyes)
• Nausea
• Vomiting
• Headache
• Dizziness
• Hair loss
• Mucosal sores
• Organ damage (liver,
kidney, bladder, lung)
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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
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
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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.
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Closed-System Drug Transfer Devices are
Recommended 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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Total Positive Urine Samples
Agent
Pre-PhaSeal
Post-PhaSeal
# positive samples*
%
Cyclophosphamide
18/48
38
Ifosfamide
10/47
21
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
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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
Objective
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).
Source: Hospital Pharmacy Vol. 43, No. 9
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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)
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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).
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Devices Tested
B. Braun OnGuard™ System
(Teva Medical LTD)
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Chemo Mini-Spike Plus™
Dispensing Pin
(B. Braun Medical Inc.)
Alaris SmartSite®
(Cardinal Health)
Devices Tested
Chemoprotect® Spike
(Codan US Corporation)
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PhaSeal®
(Carmel Pharma)
Smoke Study: Update
Spiros™ and Clave®
(ICU Medical)
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Vial Adapter and Clave®
(ICU Medical)
CyTwo-Fer
(Baxa)
CHEMO-AIDE
(Baxter)
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 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.
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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.
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Clave® Vial Adaptor
& Spiros™ Male Connector
(ICU Medical, Inc.)
B. Braun/Tevadaptor™
Vial Adaptor & Syringe Adaptor
(Teva Medical Ltd.)
22
Alaris SmartSite® Vented Vial
Access 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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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
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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.
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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 pushturn-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 13mmneck 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)
33
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
34
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
35
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
36
Results
On average, the overall cost of cytotoxic preparation can be
decreased by 7% to 15% depending on the applied scenario.
37
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
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The Value of PhaSeal
39
•
Experience
PhaSeal is supported by Carmel Pharma’s 15+ years of dedicated
CSTD research and development.
•
Quality
The 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.
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
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Questions ?
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Thank You!
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