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1
Safe Handling of
Hazardous Drugs
1.5 Contact Hours
Commercial Support Provided by:
Carmel Pharma, Inc.
Question 1
What is your primary practice setting?
A. Hospital Pharmacy
B. Long Term Care
C. Education
D. Other
2
Question 2
What is your position?
A. Pharmacy Director/Management
B. Staff Pharmacist
C. Pharmacy Technician
D. Student
. Other
Question 3
Are you familiar with the current studiesrelated to closed-system drug transferdevices?
A. Yes
B. No
C. Not Sure
3
Question 4
So far…
A. I’ve hit the jackpots.
B. I am even.
C. I’ve lost some money, but haven’t given up.
D. I don’t gamble.
. It looks like my friends and family will notbe getting any gifts this holiday season!
Program Information
• Target Audience: Pharmacistsand Certified Pharmacy Technicians
• ACPE Nos.384-000-07-024-L04-P384-000-07-024-L04-T
• 1.5 Contact Hours
• Release Date: 12/1/07
• Expires: 12/1/10
• Statements of Credit will be issuedby mail within 2 weeks.
• STAT Educational Services is accredited by theAccreditation Council for Pharmacy Education(ACPE) as a provider of continuing pharmacyeducation.
4
Contact Information
STAT Educational Services
Phone 888-247-8700
Fax 888-247-8706
E-mail [email protected]
PO BOX 683148
Houston, Texas 77268
Presentation Download Available at
www.statce.com
Learning Objectives
1. Describe the reproductive risks associatedwith exposure to chemotherapeutic agents.
2. Describe the carcinogenic potentialassociated with exposure tochemotherapeutic agents.
3. Analyze the findings from current researchand studies on closed-system drug transferdevices.
4. Present the NIOSH current recommendationsfor a medical surveillance program forhazardous drugs.
5. Describe the medical surveillance program forhazardous drugs of a community basedpharmacy.
5
Jim Jorgenson, RPh, MS, FASHP
Administrative Director for Pharmacy Services
Associate Dean for Pharmacy
University of Utah
What Defines a “Hazardous Drug”
1. Carcinogenicity
2. Teratogenicity or otherdevelopmental toxicity
3. Reproductive toxicity
4. Organ toxicity at low doses
5. Genotoxicity
6. Structure & toxicity profile for newdrugs that mimics existinghazardous drugs
6
Standards & Guidelines
Guidelines
• ASHP
• ONS
• ISOPP
• HOPA
• European Oncology
• NIOSH
Standards
• USP 797
• OSHA
• JCAHO
Why Do We Care?
The same mechanisms that thesedrugs employ to kill cancer cellsalso works to damage healthy cells
NIOSH Warning
Working with or near hazardousdrugs in health care settings maycause skin rashes, infertility,miscarriage, birth defects andpossibly leukemia or other cancers
7
OSHA
“Preparation, administration, and
disposal of hazardous drugs
may expose pharmacists,
nurses, physicians, and other
health care workers to
potentially significant
workplace levels of these
chemicals.”
8
Recent Concerns
• Increasing evidence of exposure
• Increasing numbers of cancerpatients
• More drug combinations
• Higher doses of drugs
• More potent drugs
• Increasing non-cancer use ofantineoplastics
• New treatment settings
Source = Thomas Connor, Ph.D., NIOSH
Presence of Hazardous Drugs
in the Workplace
• Numerous published studiesdemonstrating the presence ofhazardous medications in theworkplace
• Multiple studies demonstrating thathazardous drugs are present in theurine of healthcare workers includingpharmacists and technicians
9
Adverse Effects
Patients =
High doses with limited number ofdrugs over a defined time period.
Healthcare Workers =
Low doses of multiple drugs overlong periods of time
Acute Effects
• Nausea
• Vomiting
• Headache
• Dizziness
• Hair Loss
• Mucosal Sores
• Liver Damage
10
Long Term Effects
• Reproductive
• Developmental
• Genetic
• End Organ Damage
• Cancer
Reproductive Risks
• Numerous peer reviewed studies thatclearly establish a direct cause andeffect relationship between exposureto cytotoxic agents and adverseeffects
• Statistically significant differencesbetween healthcare workers exposedto these agents and the generalpopulation in terms of: spontaneousabortions, infertility, premature labor
11
Occupational Exposure to
Antineoplastic Agents
• Kaiser Permanente Center for HealthResearch
• 7,094 pregnancies of 2,976 pharmacyand nursing staff studied
• Exposure of mother to handlingantineoplastic agents duringpregnancy was associated with asignificant increased risk forspontaneous abortion and stillbirth
Journal of Occupational & Environmental Med
Vol.41; 8: 632-638
Developmental Effects
• Numerous peer reviewed studiesdemonstrating a statisticallysignificant difference in low-birthweight infants, birth defects andlearning disabilities in offspring ofhealth care workers exposed tohazardous meds during theirpregnancy
12
Teratogenicity
• Conflicting opinion on exposureduring 2nd and 3rd trimesters
• Greatest danger during 1st trimester• Hemminki case control study of
Finish oncology nurses activelyhandling chemotherapy during1st trimester
• Demonstrated statistically significantincrease in riskfor malformations
• Odds ratio of 4.7 (p=0.02)
Hemminki K, Kyyronen P, Lindbohm ML. J Epidemiol Community Hlth1985
Cancer Risk
• No question that given enoughexposure these agents can causecancer
• IARC designation
• Sessink cancer risk model forcyclophosfamide
13
Carcinogenic Potential
• IARC Group 1 Human Carcinogens(102 chemical entities)10 drugs and 2 combination therapies;cyclophosphamide, azothiaprine, busulfan, thiotepa,tamoxifen, etoposide
• IARC Group 2A Probable Carcinogens (68 chemicalentities)9 drugs; azacitadine, carmustine, CCNU, cisplatin,doxorubicin, nitrogen mustard
• IARC Group 2B Possible Carcinogens (245 chemicalentities)
• 10 drugs; dacarbazine, daunoribucin, bleomycin,mitomycin, mitoxantrone
Cancer Development
• Numerous case studies
• Significant increase in leukemia notedamong oncology nurses in the Danishcancer registry(Br J Ind Med 49:855-61)
• 39 YO pharmacist with papillarytransitional cell carcinoma(J Nat Can Inst 85(13):1089-91)
• 39YO vetrinarian with atypcial thyroidcancer
14
Genetic Effects
• Genotoxic effects noted inboth patients and healthcareworkers
• DNA single strand breaks
• Chromosomal aberrations
• Length of exposure mostsignificant factor
Demonstrated Genotoxicity
• Significant increase (2.5X) in chromosomalaberrations in nurses and pharmacy techs handlingchemotherapy compared to healthy subjects nothandling chemo (Cavaloa Abstract 2005–Publicationpending)
• Examined two oncology nurse groups, one usingPPE and one not vs. a control group. Statisticallyhigher rate of sister chromatid exchange in theunprotected group when compared to both thecontrol and protected group (p<0.001) Brumen Am JIndust Med 30:67071, 1996
• Examined lymphocyte DNA damage in oncologynurses compared to controls and demonstratedincreased DNA damage secondary to cytotoxic drughandling Yoshida, J Occup Health, 48:517-22, 2006
15
Summary
• Cancer chemotherapy presents a clearhealth hazard for healthcare workers
• Both acute and long term effects of thesemedications should be considered
• Clear cut safety precautions based onsound medical evidence should beestablished in the work place
Question 1
The National Institute of Safety andOccupational Health includes all of thefollowing elements in it’s definition of ahazardous drug except:
A. Carcinogenicity
B. Flammability
C. Teratogenicity
D. Genotoxicity
16
Question 2
Which of the following drugs has beenclassified by the International Agency forResearch on Cancer as Group I, a knownhuman carcinogen?
A. Mitomycin
B. Doxorubicin
C. Cyclophosphamide
D. Bleomycin
Susan M Spivey, DDS,PharmD
Ambulatory Treatment Center Pharmacy ManagerUT M.D. Anderson Cancer Center
17
Routes of Exposure
• Dermal- direct contact w/drugsor contaminated surfaces
• Oral Ingestion – food, gum,hand to mouth
• Inhalation
- Particulates (droplets, dusts)
- Vapors
• Injection – sharps , breakage
Surface Contamination Studies
• 27 Published studies
• All studies detected measurablelevels of at least one drug
• Contaminated areas included:biological safety cabinets, floors,counters, IV bags, keyboards,gloves, transport containers,patient tables, chairs, wastecontainers
18
Surface Contamination Studies
• In 1999, Connor et al. demonstratedsurface contamination withcyclophosphamide, ifosfamide andfluorouracil in pharmacy and patienttreatment areas in three hospitals inthe U.S. and three in Canada
Surface Contamination Studies
• 75 % of pharmacy and 65 % ofpatient treatment areas werecontaminated with at least oneof the three drugs
• Drugs were detected in adjacentareas where drugs were nothandled
(Connor et al, 1999)
19
Air Sampling Studies
• 16 Published studies
• Particulate collection on paper orglass filters
• Low percentage of samples containeddrugs
• Drug levels were usually low
Fluorescein Study
Conventional Needle/ SyringeTechnique
vs
Utilizing PhaSeal
(S M Spivey, T H Connor 2003)
20
Fluorescein Study
• Fluorescent dye
• Inspected with UV light
• Evaluated fluorescein release into thework environment
Fluorescein Study
Evaluated
-Drug Reconstitution
-Drug Transfer ( vial- IV bag)
-Drug Administration/Disconnection
21
Drug Reconstitution With Needle and Syringe
Drug Preparation with PhaSeal®
22
Drug Transfer with Needle and Syringe
Drug Transfer with PhaSeal®
23
I.V. Push with Needle and Syringe
I.V. Push with PhaSeal®
24
Needle/Syringe vs PhaSeal®
Using Fluorescein
Release of fluorecein
Closed
Needle/Syringe System
Reconstitution YES NO
Drug Transfer YES NO
Vial-Bag Administration YES NO
I.V. Push YES NO
Fluorescein Summary
• All phases of the conventionalneedle/syringe technique resulted inrelease of drug into the environment
• Most surface contamination was 1-4mm in diameter, but some wereconsiderably larger.
25
Summary
• Total of 75 manipulations
• No fluorecein release was detectedwith PhaSeal.
2006 Utah Protocol
University of UtahEvaluation of Vial Transfer Devices for
Containment of Hazardous Drug Vapors
(C Au, J A Jorgensen, B Smith 2006)
26
Objective
Examine commercially availabledrug transfer devices anddetermine which products meetthe NIOSH definition of a closed-system drug transfer device(CSTD).
NIOSH Definition
“A closed-system drug transfer devicemechanically prohibits the transfer ofenvironmental contaminants into thesystem and the escape of hazardousdrugs or vapor concentration outsidethe system”
27
Methods
• Evaluated five systems
– B.Braun OnGuard System withTevadaptor components—Vial adaptor
– Alaris Smart Site® Vented VialAccess Device
– PhaSeal ® Protector 50 andInjector Luer lock
– Chemoprotec Spike® (Codan)
– Chemo Mini Spike Plus™Dispensing Pin
Methods
• Titanium tetrachloride
– Simulates the escape of cytotoxicvapors
– Generates visible smoke when incontact with air
• Titanium tetrachloride added to eachvial (3 ml) and crimp sealed
• Each vial was spiked with eachindividual product
28
Methods
• 60 ml syringe with 50 ml airwas attached to each device
• Air was injected over 10 seconds
• Photographs and videos were takento record any escape of titanium fromeach product
• Filters were tested for potentialdamage from hydrochloric gasor titanium dioxide
Engineering Controls
Closed systems drug transfer device
Mechanically prevent the transfer ofenvironmental contaminants into thesystem and the escape of drug or vaporout of the systems.
Phaseal
Many more competitors in the market
Not a substitute for ventilated cabinets
29
2006 Utah Protocol
Results
• The PhaSeal® System was the onlysystem to prevent the release oftitanium smoke from the closedsystem drug transfer device
• PhaSeal® was the only device thatmet the NIOSH definition of a closed-system drug transfer device.
30
Parallel Fluoroscein Studies
Conducted byU. T. M. D. Anderson Cancer Center
and The University of Utah
S M Spivey, J A Jorgenson 2007
Objective
Evaluate the potential to releasefluorescein into the environment in thepreparation and administration phases.
• B.Braun OnGuard Systemw/Tevadaptor components
• Cardinal/Alaris System
• PhaSeal® System/Carmel Pharma
31
Methods
Preparation Phase
• 0.05% Fluorescein dye 15ml/20mlvial
• 5 mls withdrawn and 1ml reinjectedinto vial
• Vial adaptor and syringecomponents were disengaged,observed and photographed underuv light and touched to a 4 x 4gauze.
Methods
Administration Phase
• Simulation of a 7 ml IV push
• Observing the syringe adaptors andIV port device for each product
32
Alaris Smart Site®/Texium™
(Cardinal Health)
Alaris Smart Site®/Texium™
(Cardinal Health)
33
Touch Test - Alaris Smart Site®/Texium™
(Cardinal Health)
BBraun OnGuard System Tevadaptor™ Vial
Adaptor & Tevadaptor™SSyringe Adaptor
(Teva Medical, Ltd)
34
BBraun OnGuard System Tevadaptor™ Vial
Adaptor & Tevadaptor™SSyringe Adaptor
(Teva Medical, Ltd)
Touch Test - BBraun OnGuard System
Tevadaptor™ Vial Adaptor & Tevadaptor™
Syringe Adaptor (Teva Medical, Ltd)
35
PhaSeal® Protector
(Carmel Pharma)
PhaSeal® Protector & Injector Luer
(Carmel Pharma)
36
Touch Test - PhaSeal® Protector &
Injector Luer (Carmel Pharma)
ResultsPreparation Phase
0%87%
77%Touch Test
0%67%47%Syringe
Adaptor
0%80%56%Vial Adaptor
PhaSeal®System
Cardinal/AlarisSystem
BBraunOnGuard
System
37
ResultsAdministration Phase
0%100%60%TouchTest
0%100%60%IV Port
0%80%60%SyringeAdaptor
PhaSeal® System
Cardinal/
Alaris
System
BBraun
OnGuard
System
Results
• B.Braun’sOnGuard/Tevadaptor™System and Cardinal Health/AlarisSystem showed visible fluoresceinleaks on each component duringdrug preparation and administrationphases
• PhaSeal® System showed no visiblefluorescein leakage during thepreparation and administrationphases
38
2007 Utah Protocol Update
University of UtahEvaluation of Vial Transfer Devices for
Containment of Hazardous Drug Vapors
(C Au, J A Jorgensen, B Smith 2007)
Objective
Examine commercially available drugtransfer devices and determine whichproducts meet the NIOSH definition of aclosed-system drug transfer device(CSTD).
39
2007 Utah Protocol Update
Results
• The PhaSeal® System was the onlysystem to prevent the release oftitanium smoke from the closedsystem drug transfer device
• PhaSeal® was the only device thatmet the NIOSH definition of a closed-system drug transfer device.
40
Leakproof Connection
Integrity Test
For Devices Intended for
Handling Hazardous Drugs
(J A Jorgensen 2007)
Objective
• To determine if the ICU MedicalSystem, B. Braun/Tevadaptor™System, Cardinal/Alaris System orPhaSeal® System connections areleak proof or have the potential toallow drugs to escape into theenvironment during the preparationand administration phases ofhazardous drug handling.
41
Methods
• Four transfer devices were tested
• A liquid with low pH was used as a substitute foractive drug. Litmus paper was used as pH indicator.Blue litmuspaper turns red under acidic conditions.
• Syringes were filled with fluid and injected into vialsattached to the above transfer devices. Afteraspirating back and disconnecting, the connectionsof each device were pressed against litmus paper todetect the presence of any fluid.
• Every component of each device was tested for 10 manipulations.
Clave® Vial Adaptor & Spiros™ Male
Connector (ICU Medical, Inc.)
42
B. Braun/Tevadaptor™ Vial Adaptor &
Syringe Adaptor (Teva Medical Ltd.)
Alaris SmartSite® Vented Vial Access Device
& Texium™ Male Luer (Cardinal Health)
43
PhaSeal® Protector & Injector Luer Lock
(CCarmel Pharma)
Results
• Visible leakage occurred outside ofthe components on the ICU MedicalSystem Clave® and Spiros™connections, the B.Braun/Tevadaptor™ System and theCardinal Health/Alaris System duringall manipulations.
• No leakage was observed in any ofthe manipulations with the PhaSeal®System.
44
Make Sure You Know
What You’re Getting….ASK
• If the device uses a filter to equalizethe air pressure, it is not a closedsystem
• Ask for Clinical Studies, peer reviews,or independent studies (white papersare not acceptable)
• The device must meet therequirements of closed-system drugtransfer device as defined by NIOSH
Question 1
What are characteristics of a closed-system drug transfer device?
A. Mechanically prohibits transfer ofenvironmental contaminants intothe system
B. Does not allow escape of hazardousdrugs
C. Does not allow the escape of vapors
D. All of the above
45
Question 2
What is important to know before choosing aclosed-system
drug transfer device?
A. Peer reviews, independent studies, and/orclinical studies exist on the product.
B. The product must meet the NIOSH definitionof a closed system
C. Does the device have filters that let airescape
D. All of the above
Dr. Paul J.M. Sessink, PhD
Exposure Control B.V., FounderThe Netherlands
www.exposurecontrol.nl
46
Toxicity of Antineoplastic Drugs
Acute effects
• Irritation (skin, eyes)
• Alopecia
• Nausea
• Vomiting
• Diarrhea
• Organs (liver, kidney,bladder, lung)
• Bone marrowsuppression
Delayed effects
• Reproductive effects– Spontaneous
abortions– Malformations
off-spring– Low birth weight– Prolonged time to
pregnancy• Menstrual dysfunction• Mutagenicity• Carcinogenicity
– Genotoxic/Non-genotoxic
– IARC classification
Genotoxic Carcinogens
Mechanism of Action
• Absence no-adverse-effect level supposed:
one molecule is able to induce cancer !
• Exposure has to be avoided
• Workers need to be protected
• Safety guidelines and protectivemeasures
• Monitoring of the workers
47
Council Directive European Union
Carcinogenic Compounds 28 June 1990
STRATEGY (decreasing priority)
1) replacement by a less toxiccompound
If not possible
2) reduce sources of exposure
If not possible
3) ventilation
If not possible
4) personal protection
Council Directive European Union
Carcinogenic Compounds 28 June 1990
STRATEGY FOR ANTINEOPLASTIC DRUGS
1) replacement by a less toxic compound
Impossible
2) reduce sources of exposure
Closed systems
3) ventilation
Clean rooms with BSCs
4) personal protection
Gloves, gowns, masks, specialclothes, …
48
Environmental and Biological Monitoring
Environmental Monitoring
• Measures thepresence/release of thedrug in the environment
• No information aboutuptake of the drug in thebody of the worker
• No information abouthealth-risk for theworker
Biological Monitoring
• Assessment ofuptake of the drug
in the body of theworker
• Estimation of health-risk for the worker
Monitoring Antineoplastic Drugs
Exposure Control B.V.
Environmental Monitoring
• Cyclophosphamide 0.1 ng/mlsample
• Ifosphamide 0.1 ng/mlsample
• 5-Fluorouracil 20 ng/mlsample
• Methotrexate 5 ng/mlsample
• Platin compounds (cis-platin & carbo-platin) 0.2 ng/mlsample
• Etoposide 50 ng/mlsample
• Mitomycine C 100ng/ml sample
Analysis:HPLC, GC-MSMS, Voltammetry
49
Monitoring Antineoplastic Drugs
Exposure Control B.V.
Biological Monitoring (urine)
• Cyclophosphamide 0.1 ng/mlsample
• Ifosphamide 0.1 ng/mlsample
• 5-Fluorouracil (a-fluoro-ß-alanine) 20 ng/mlsample
Analysis:GC-MSMS
Sources of Contamination
and Potential Exposure
• External vial contamination
• Spillage during preparation andadministration(handling technique)
• BSC/isolator
• Patient (urine, sweat, vomit,blood, faeces)
• Waste
• Laundry and clothing patient
50
Glove Contamination During
Preparation of Antineoplastic Drugs
19 – 1564Methotrexate
16 – 1040105-Fluorouracil
371Cyclophosphamide10
220 – 19002Methotrexate
21 – 620115-Fluorouracil
1.5 – 9.68Cyclophosphamide17
Range ( g/pair)N(pos)DrugPair of gloves
Contamination BSC
+--4
--+3
++++++2
+++1
After alcoholcleaning
Afterpreparation
Beforepreparation
Day
Drugs analyzed: cyclophosphamide - 5-fluorouracil -methotrexate
+ one drug detected++ two drugs detected+++ three drugs detected- no drugs detected
Conclusion: contamination and ineffective cleaning procedure
51
Surface Contamination with Cyclophosphamide
in Preparation Areas (ng/cm2)*Connor et al., Am J Health-Syst Pharm 1999; 56:1427-32
0.010.090.14-0.190.01-0.13
Floor entrancepreparation
room/corridor
0.01-0.020.160.52Floor entrancepreparation room
0.01-0.360.03-0.190.02Table top not forcyto preparation
0.01-0.021.771.240.15-0.310.01-2.360.11-0.16Floor centralpreparation room
0.01-0.030.051.790.05-0.550.03-2.400.05-0.32Floor under BSC
0.01-1.1614.02-14.224.74-15.320.13-6.610.05-40.130.01-2.63Table top cytopreparation/BSC
NetherlandsGermanySwedenBelgiumUSA*Canada*Description surface
Surface Contamination with Cyclophosphamide
in Administration Areas (ng/cm2)*Connor et al., Am J Health-Syst Pharm 1999; 56:1427-32
0.02-0.090.01-0.59Floor corridor/awayfrom administration
0.03-0.50Arm rest chair visitorspatient
0.01-0.07Floor toilet patients
0.090.01Top patients table
0.09-1.49Arm rest chair patient
0.01-7.370.03-0.640.01-1.00Floor near bed patient(infusion pole)
NetherlandsUSA*Canada*Description surface
52
Surface Contamination with
Cyclophosphamide in Preparation Areas
Reduced with PhaSeal*Sessink et al., submitted to Am J Health-Syst Pharm
P < 0.0001
0.030.03< 0.01-0.90< 0.01-122.2729Counter
0.010.14< 0.01-16.33< 0.01-34.7629Floor in front of BSC
0.203.860.01-17.15< 0.02-158.0026BSC airfoil
0.020.13< 0.01-5.41< 0.01-17.1930BSC surface
PhaSealStandard
techniquesPhaSeal
Standard
techniques
MedianMin-MaxNSurface
Cyclophosphamide (ng/cm2)
22 US Hospital
Pharmacies
2001-2005
Vapor Pressure Antineoplastic DrugsKiffmeyer et al., Pharm J 2002; 268:331-7
0.080.00141305-Fluorouracil
0.630.0026289Etoposide
0.360.0033261Cyclophosphamide
0.220.0018300Cisplatin
1.70.019214Carmustin
Max.
concentration
(mg/m3)
Vapor
pressure
(Pa) at
20°C
Mol.
Weig
ht
Antineoplastic
Drug
Conclusions
– Antineoplastic drugs possess a low vapor pressure
– Maximum concentrations possible by insufficient ventilation
– Protective clothes and equipment are not designed to protectworkers from vaporized antineoplastic drugs
– Additional health-risk ?
53
Cyclophosphamide (CP) in Urine of Dutch
Technicians Preparing Antineoplastic Drugs
0.1836476851-8
0.0924088
0.1014287
0.0126986
0.07683165
0.231199164
0.1864783
0.1223182
0.53665131
Mean CP
( g/day)
Number of positive
samples
Number of urine
samples
Number of
days
Technician
Cyclophosphamide (CP) in Urine of Dutch
Nurses Administrating Antineoplastic Drugs
0.8016103161-7
0.2211127
0.4252846
001425
001224
0.2321723
0.573922
4.1351221
Mean CP
( g/day)
Number of positive
samples
Number of urine
samples
Number of
days
Nurse
54
Additional Cancer Risk
Exposure to Cyclophosphamide
• Technicians
– 0.18 g CP inurine/day
– 1.4-10 extracancer cases amillion workers ayear
• Nurses
– 0.80 g CP inurine/day
– 10-50 extra cancercases a millionworkers a year
• Prohibitory risk level
– 100 extra cancercases a millionworkers a year
• Strive risk level
– 1 extra cancer casea million workers ayear
• Conclusion
strive risk level not
achieved
too high exposurelevels
Cancer Risk Level in Relation to Environmental
Contamination with Cyclophosphamide
YesYesYesNow and
thenMonitoring
YesStop
working
YesImmediately
YesAt shortnotice
NoAction
> 101.0 – 100.1 – 1< 0.1Contamination CP (ng/cm2)
> 20.2 - 20.02 – 0.2< 0.02Urine CP ( g/24 hr)
Prohibitoryrisk level
Striverisk level
55
Conclusions
• Antineoplastic drugs are spread in theenvironment during preparation, administration,patient care and waste handling
• Healthcare workers are exposed toantineoplastic drugs
• The main exposure routes are:
– Dermal uptake contact with contaminatedsurfaces
– Inhalation particles (vapors?)
• Additional cancer risk for hospital workershandling antineoplastic drugs (nurses >technicians)
• Vials are mostly contaminated
• Gloves are always contaminated
• Avoid open connections– Do not disconnect systems
Question 1
Based on the current knowledge what isconsidered to be the most importantexposure route of antineoplastic drugs forhospital workers?
A. Inhalation
B. Ingestion
C. Skin Permeation
56
Question 2
Protective gloves used for preparation ofantineoplastic drugs should be changed:
A. Once a day
B. After each shift
C. Every 2 hours
D. Every 30 minutes
Firouzan ‘Fred’ Massoomi,
Pharm.D., FASHP
Pharmacy Operations CoordinatorNebraska Methodist Hospital
Omaha, Nebraska
57
Nebraska Methodist Hospital
Department of Pharmacy Services
• Scope of Department• In-patient Pharmacy Services• Home Infusion• Anesthesia Support Services• Cancer Center Infusion• Ambulatory Anticoagulation Service
• Fully automated dispensing– Pyxis, AutoMed, BAXA, McKesson, Cerner
• Bedside barcode scanning, 100%• USP <797> & NIOSH compliant work space
– Cleanroom 400 sqft; IV Workroom 380 sqft; HD room 160sqft
• 51 FTE’s, equating to 90 team members– 40 RPhs, 26 PharmTechs, 10 Interns, 4 RN’s, 3 Anesthesia Techs, 2 LPN’s
• Formal decentralized clinical services Centralized services
•• M-F; 7am to 10pm; M-F; 7am to 10pm; 24/ 724/ 7
2006 Automated Dispensing
1,004,967 Oral doses
235,742 IV Push, topicals (etc.)
2006 Sterile Compounding
285,548 Large volumes
301,902 Sterile Products
Low and medium risk
10,392 “Hazardous drugs”
Nebraska Methodist Hospital
Department of Pharmacy Services
Dispensing Statistics
58
“Workers may be exposed to a hazardous
drug at many points during its manufacturer,
transport, distribution, receipt, storage,
preparation, and administration…..Exposure
to these drugs in the workplace has been
associated with acute and short-term
reactions, as well as long-term effects”
ASHP Guidelines on Handling Hazardous Drugs
Am J Hosp Pharm 2006
“Studies have associated workplace
exposures to Hazardous Drugs with health
effects such as skin rashes and adverse
reproductive outcomes (including infertility,
spontaneous abortions, and congenital
malformations) and possibly leukemia and
other cancers”
NIOSH Alert: Preventing Occupational Antineoplastic andOther Hazardous Drugs in Health Care Settings
CDC 2004
59
Advent of Modernday chemotherapy
Loius Goodman andAlfred Gillmon use
nitrogen mustard totreat non-Hodgkin’s
Lymphoma
First review ofcarcinogenicpotential ofanticancer drugs
“The carcinogencityof anticancer drugs:
A Hazard in Man”
First case reportof occupationalexposure riskwith HDs
“Mutagenicity in the
urine of nurses
handling cytostatic
agents”
1981
First publishedguidelines forhandling HDs
“Developing guide-
lines for working
with antineoplastic
drugs”
1942 1983
American MedicalAssociationguidelines forHDs
“Guidelines for
handling parenteral
antineoplastics”
1985
Risk defined foroccupationalexposure to HDs
“Risk of handling
injectable
antineoplastic
agents”
American Societyof HospitalPharmacistsTechnicaladvisory bulletin(TAB) on handlingcytotoxic andhazardous drugs
OSHA TechnicalManual: Control-
ling occupational
exposure to HDs
Chapter 21.(OSHA instructionCPL 2-2.20B CH4)
OSHA TechnicalManual Update:Controlling
occupational
exposure to HDs
OSHA instructionTED 1-0.15ASection VI.Chapter 2
First USevaluation ofPhaSeal“Evaluation of the
PhaSeal
hazardous drug
containment
system”
USP <797>”Pharmaceutical
compounding-Sterile
preparations”
American Societyof Health-SystemPharmacistsGuidelines onhandlinghazardous drugs
1990 1995 19991976 1979 2004 2006
NIOSH AlertPreventing
occupational
exposure to
antineoplastic and
other HDs in
healthcare settings
Timeline of Significant Studies andTimeline of Significant Studies and
Guidelines for Hazardous DrugsGuidelines for Hazardous Drugs
2007
DHHS NIOSH2007-117 “Medical
Surveillance for
health care
workers exposed to
HDs”
Guidelines for Hazardous Drugs
Source Year
ASHP 1985, 1990, 2006
NIOSH Alert 2004, 2007
OSHA 1986, 1996, 1999
Oncology Nursing Society 1988, 2003
AMA Council on Scientific Affairs 1985
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OSHA and NIOSH Standards
• Occupational Safety and Health Administration(OSHA)
– Author Agency: US Department of Labor
– US Labor Laws
• OSHA Technical Manual: ControllingOccupational Exposure to Hazardous Drugs
1999
• National Institute for Occupational Safety & Health(NIOSH)
– Authoring Agency: Centers for Disease Control
– US Practice Standards
• NIOSH Alert: Preventing OccupationalExposures to Antineoplastic and OtherHazardous Drugs in Health Care Settings
August 2004
NMH Approach to Handling
Hazardous Drugs
• Sub-committee of Hazardous Material Committeeformed in early 2005
• Representation by Nursing, Pharmacy,Human Resources, Safety, Surgery,Radiology, Performance Improvement,Employee health, House Keeping
• Goals– Address national compliance standards to
daily practices to ensure patient and employeesafety
– Compare practices to nationally approvedlabor laws and practice standards
– Conduct a Gap Analysis of policy to practice– Formally present findings– Implementation strategies
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Process of Gap Analysis
• Initial knowledge level of key stakeholders: low
• Formal education through presentations
• Required reading of OSHA & NIOSH
• Preparation of Gap Analysis Grid to assess compliance
• Supporting documentation through policies to practice
• Practice in most cases dictated compliance
• Analysis of sites outside of Methodist Hospital
• Grid may be used as a tool for compliance
to clinics
• Site visits to two outside clinics demonstrated lack ofcompliance toOSHA and EPA regulations
Hazardous Drugs
“Pharmaceutical agents are classified as hazardous drugs if
studies in animals or humans indicate their potential to cause
cancer, developmental or reproductive toxicity, or harm to
organs”
• When it occurs at low doses
ASHP 1990; OSHA 1995, 1999
• Appendix A of NIOSH Alert
• antineoplastics; Immunosuppressive agents;Estrogens; Oxytocics; Contraceptives; 5-alphareductase inhibitors; Androgens; Antivirals;Gonadotropins; Anti-infectives; Estrogen agonist-antagonists; Skin mitotic inhibitors; Cell stimulants andproliferants
• All forms of drugs
• How do we tell if it is Hazardous?
– No Universal symbol to designate
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Sources of Exposure
• Drug vials
• Drug preparation
• Spills
• Vapor
• Drug administration
• Patients
– Waste & laundry
• RX Waste
Workers at risk
• Shipping/receiving
• Pharmacy personnel
• Nursing personnel
• Physicians
• OR personnel
• Environmentalservices
• Laundry services
• Waste management
Exposure & Risk
Work Environment
Traditional Biological Cabinet Isolator Glove Box
Not exempt from garbing requirements
NuAir, ChemoShield
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Storage and Compounding
• Evaluation of work environment & equipment
• Policy & Procedures
– delineation of hazardous materials
• develop list with Safety departments
– Labeling, storage, personnel issues, spillcontrol
– Education, preparation, administration,disposal
• Evaluation of workspace
– Ventilated cabinets
• Use of equipment or devices to minimizeexposure
– Needle-less
– Personal Protective Equipment
– Closed-system devices
Decontamination
• “Decontamination” of cabinets– Surface-safe (15/case) $1.43/ea
• step 1: 2% sodium hypochlorite detergent• step 2: 1% sodium thiosulfate & 0.9% benzyl alcohol• 6% Hypochloride solution
– azathioprine, bleomycin, daunorubicin, etoposide,fluorouracil, etoposide, mitomycin, vinblastine,vincristine
– cyclophosphamide, melphalan, ifosfamide, methotrexate
• “Sterilization” of cabinets– Caution Isopropyl alcohol use in Type II-A and II-B3– Must be in contact for 30 seconds
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Administration and Cleaning
• Administration
• Skills assessed for administration
All personnel including MD’s
• Policy on tubing sets not removed from original bags
• Housekeeping and Decontamination
• All waste placed appropriate waste containers & labeled
• Routine cleaning of work environments
and rooms??
• PPE for Environmental Services??
• Blood and Urine specimens???? in the pneumatictubes?
• Linen management
• All linen bagged in yellow bags peri andpost chemo
• Linen personnel to don appropriate garb
RCRA HazardousWaste Containers
Hazardous Pharmaceutical
Waste Streams
Biohazard InfectiousWaste (Regulated Medical Waste)
Blood products, sharps, items
contaminated with liquid blood, etc.
Trace Chemo Waste Containers
RCRA empty chemotherapy vials,
syringes, IVs, tubing, gowns,
gloves, etc.
Bulk chemo in vials,
unused IV’s, P, U. toxic & ignitable D
Overtly contaminated gowns, glove,
chemo spill clean up materials
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Education Plan
• Orientation to hazardous chemicals
- Key contacts within the organization
- Location of policies
• Encourage employees to notify their physician of theirpossible occupational exposure to hazardous drugs
• Educate employees of signs and symptoms
- Based on the agents
- Acute versus chronic
- Annual review of critical process and hazardouschemicals
- Plan in place to education on new chemicals
Staff Education Program
Medical Surveillance
– Recommendations since 1985
– NIOSH 117 document April 2007
• www.cdc.gov/niosh/docs/wp-solutions/2007-117/NIOSH
- Recommendations, NOT a mandate
– Elements of a medical surveillance program
- Reproductive and health questionnaires- at hire and periodically
- Laboratory work- Complete blood count & Urinalysis
- Physical examination at hire and thereafter forabnormal findings on health questionnaire
- Follow-up for those workers who have health changesor significant exposures
- Tracking trends with questionnaires and sick-call
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Occupational Safety and Health Association (OSHA)
Centers for Medicare and Medicaid Services
The Joint Commission
United States Environmental Protection Agency (USEPA)
State Boards of Health (Nursing, Pharmacy, etc.)
Agencies That Could Be Involved
with Hazardous Drug Exposures
The Joint Commission VisitNovember 27 to 30, 2007
• Tracer on a Oncology patient
– Started from admission to point of administration ofNovember 28, 2007 Cyclophosphamide dose
– Visited pharmacy to observe compounding
• Use of NuAire Isolator
• Use of full garb with the Isolator
• Use of PhaSeal
• Use of Black delivery bags & RCRA waste containers
– Interviewed compounding pharmacist
• Stated ‘Nice to not have to worry about beingexposed’
• Surveyor commented in exit interview
– “Very impressive system from patient care unit to thepharmacy utilizing an isolator and the PhaSeal system”
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NMH Process Changes
• Education of Hazards Plan
• New employee orientation & annual review
• Team meetings: pharmacy, housekeeping, nursing
• Garbing Requirements
• Shipping/receiving, housekeeping, contractors, laundry
• Segregation of regulated waste
• Defined red, yellow and black (RCRA) waste
• Signage for Hazardous Drug Use
• Signage in pharmacy where HDs are stored
• Magnets on doors of patients receiving treatment
• Medical Surveillance
• Analysis of sick-call for high risk team members
- follow-up call for all at-risk members
• Compounding personnel only, new for 2008
“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”
OSHA Technical Manual: Controlling OccupationalExposure to Hazardous Drugs
US Department of Labor 1999
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Question 1
A comprehensive safety program formanaging hazardous drugs shouldinclude:
A. Gap analysis of current processes tostandards
B. Education and Medical surveillance of highrisk personnel
C. Incorporation of engineering controls toprotect personnel
D. All of the above
Question 2
Medical surveillance is mandated under theOccupational Safety and HealthAssociation (OSHA)?
A. True
B. False
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Questions…
Question 1
Were you previously informed of thestudies/research presented today?
A. Yes
B. No
70
Question 2
Will you change your approach topractice as a result of this program?
A. Yes
B. No
C. Undecided
Thank You!
Commercial Support
Provided By
Carmel Pharma, Inc.