Safe Handling – Recommendations & Best Practices

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Safe Handling Recommendations Best Practices

• Presented by
• ltUPDATEgt

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Disclosure

• ltUPDATEgt
• 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.

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CPE Program Information

• ltUPDATE FORgt
• ltACPEgt
• ltANCCgt
• ltASHRMgt
• QuestionsSTAT Educational Servicesphone
  888-247-8700fax [phone]

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Program Learning Objectives

• At the completion of this program, participants
  should be able to
• Evaluate emerging data on the potential high
  risks of handling hazardous drugs.
• 2. Outline new recommendations and guidelines for
  personnel handling hazardous drugs.
• 3. Analyze the effectiveness of closed-system
  drug transfer devices using new published
  research/data.

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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

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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)
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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 214181-9.

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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
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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)

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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
  

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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 (p0.02)
• Source Hemminki K, Kyyronen P, Lindbohm ML. J
  Epidemiol Community Hlth 1985

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Modes of Contact for Drug Exposure to Healthcare
Worker

• Dermal
• Direct contact
• Contaminated surfaces
• Ingestion
• Food, gum
• Hand-to-mouth
• Inhalation
• Aerosols
• Vapors

• Injection
• Sharps
• Breakage

Most common source of exposure (NIOSH, 2004)
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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

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Drug Reconstitution With Needle Syringe

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Drug Transfer With Needle Syringe
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Transfer of Contamination from IV Bag
Photographs courtesy of L. Hampton, RN, MS, FNP
Donayre Cancer Center, Whiteville, NC.
Reproduced with permission.
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Chemotherapy on Plastic-Backed Pad
Photograph courtesy of L. Hampton, RN, MS, FNP
Donayre Cancer Center, Whiteville, NC.
Reproduced with permission.
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Where Else?
Photographs courtesy of L. Hampton, RN, MS, FNP
Donayre Cancer Center, Whiteville, NC. Reproduced
with permission.
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On the Floor
Photograph courtesy of Libby Hampton, RN, MS,
FNP Donayre Cancer Center, Whiteville, NC.
Reproduced with permission.
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Surface contamination with antineoplastic agents
in six cancer treatment centers in Canada and the
United States
Thomas H. Connor, Roger W. Anderson, Paul J. M.
Sessink, Larry Broadfield, Luci A. Power

• Objective
• This study was designed to demonstrate the
  presence of ctyotoxic drugs in the workplace.

Source AJHP 1999. 561427-32.
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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. 561427-32.

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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. 561427-32.

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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)

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Using a closed-system protective device toreduce
personnel exposure to antineoplastic agents
Catherine Wick, Matthew Slawson, James Jorgenson,
Linda Tyler,Huntsman Cancer Institute, Salt Lake
City, Utah

• 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
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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 RNs
  and RPhs 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

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Contamination Comparison of Transfer Devices
Intended for Handling Hazardous Drugs
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

• 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.
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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

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PhaSeal Protector, Injector Luer Lock Y-site
Connector by Carmel Pharma
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Alaris Smartsite Texium by Cardinal Health
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B. Braun OnGuardVial Adaptor, Syringe Adaptor
Luer Lock Adaptorby Teva Medical Ltd.
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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.

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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.

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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.

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Clave Vial Adaptor Spiros Male Connector (ICU
Medical, Inc.)
B. Braun OnGuardVial 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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Results

• 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.

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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

• Source OSHA Technical Manual Controlling
  Occupational Exposure to Hazardous Drugs US
  Department of Labor 1999

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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

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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
  2007www.cdc.gov/niosh/docs/wp-solutions/2007-117/
  NIOSH

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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

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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

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Environmental and Biological Monitoring

• 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

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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

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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

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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

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Sessink Model
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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 ASHPGullo, 1988OSHA, 1990, 1995 USP
  797 revisions (2007)

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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

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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

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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

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Training on Handling of Hazardous Medications

• Decontamination Procedures
• Decontamination of cabinets
• Surface Safe (15/case) 1.43 each
• Step 1 2 sodium hypochlorite detergent
• Step 2 1 sodium thiosulfate 0.9 benzyl
  alcohol
• 6 Hypochloride solution
• Combination of surface safe cationic soap
  solution
• Sterilization of cabinets
• Caution isopropyl alcohol use in Type II-A and
  II-B3
• Must be in contact for 30 seconds
• Source Massoomi, 2007

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Training on Handling of Hazardous Medications

• Appropriate Personal Protective Equipment (PPE)
• Gloves
• Use good-quality gloves made of latex, nitrile,
  polyurethane, neoprene, or other materials that
  have been tested with hazardous drugs.
• Select powder-free gloves.
• Inspect gloves for visible defects.
• Wear double gloves for drug preparation.
• Change gloves every 30 minutes or immediately if
  damaged or contaminated.
• Eye Protection
• When splashing is possible
• Source Safe handling of cytotoxic drugs an
  independent study module. 2nd ed. Pittsburgh
  (PA) Oncology Nursing Society 1997. p26

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Training on Handling of Hazardous Medications

• Appropriate Personal Protective Equipment (PPE) -
  continued
• Gowns
• Wear gowns that are disposable, made of a
  lint-free, low-permeability fabric.
• They should have a solid front (back closure) and
  knit or elastic cuffs.
• Laboratory coats and other cloth fabrics absorb
  fluids, so they provide an inadequate barrier to
  hazardous drugs and are not recommended.
• The existing guidelines do not contain a
  recommendation for the maximum length of time
  that a gown should be worn. Because no
  recommendations are stated in the literature, at
  a minimum, change the gown every time it is
  contaminated or gloves are changed.
• Respirator/masks
• For aerosols spill clean-up
• Source Safe handling of cytotoxic drugs an
  independent study module. 2nd ed. Pittsburgh
  (PA) Oncology Nursing Society 1997. p26

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Staff Education Training

• Educator/CNS Role Accountability
• Competence
• Theory
• Principle
• Validation
• Practical application
• Skill
• Documentation
• Initial
• Annual
• PRN

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Staff Education Training

• Continuous Assessment
• Inservices
• Products
• Studies
• Modification/revision
• Defect
• Incidence report

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Factors to be considered when selecting a
closed-system drug transfer device system.
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ISOPP Standards of Practice

• Know Your Risk
• Staff Training
• Levels of Protection
• Closed-System
• Definition
• Clinical Evidence

ISOPP International Society of Oncology
Pharmacy Practice J Onc Pharm Pract 2007 13
Suppl.
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What is the Risk?

• Hazardous drug exposure
• Skin rashes
• Infertility
• Miscarriages
• Birth defects
• Malignancy
• Leukemia
• Other cancers

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Staff Training

• Aseptic technique
• Safe handling of hazardous drugs
• Ongoing feedback
• Annual competency training
• Assessment/review on a regular basis
• Multi-disciplinary approach

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Levels of Protection

• Level 1 Elimination/substitution/replacement
• Level 2 Isolation of the hazard/source
  containment
• Level 3 Engineering controls/Proper ventilation
• Level 3b Administrative controls/ Organization
  measures
• Level 4 Personal protective equipment (PPE)

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What is a Closed-System?

• A closed system drug transfer device
  mechanically prohibits the transfer of
  environmental contaminants into the system and
  the escape of hazardous drug or vapor
  concentrations outside the system
• NIOSH

National Institute for Occupational Safety
Health
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What is the Clinical Evidence?
63
(No Transcript)
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Questions to ask when evaluating a drug transfer
device

• Does the device have independent, peer-reviewed
  clinical evidence that proves the efficacy in
  reducing surface contamination?
• Does the device have more than one piece of
  clinical evidence?
• Does the device have any published data that
  shows that healthcare workers will not excrete
  chemotherapy in their urine if the product is
  used?
• Does the device integrate with all phases of
  preparation, administration, and disposal?
• Can you reconstitute powdered medications with
  the device?

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Questions to ask when evaluating a drug transfer
device (cont)

• 6. Does the system have universal capability
• 7. Does the product remain closed throughout
  multiple manipulations in preparation and
  administration as defined in the NIOSH and ISOPP
  guidelines as the standard?
• 8. Does the device protect over a full spectrum
  of hazardous drugs?
• Was the device beta tested by a third party for
  this product?
• Does the company offer ongoing clinical support
  and safe handling training/education for all
  staff?

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Plan of attack..

• Cytotoxic Drug Handling
• NIOSH Official Statement
• ISOPP Standard of Practice
• Overview of our testing of the product.
• Explanation
• Data overview
• Cost