DEVELOPING STANDARD PROCEDURES FOR SAFE HANDLING
OF CYTOTOXIC DRUGS
HARBANS DHILLON
Senior Pharmacist
University Malaya Medical Centre
Kuala Lumpur
APOPC JAKARTA 2012 1
OBJECTIVES
Definition of cytotoxic drugs
Who is at risk?
Sources of contamination
Routes of exposure
Goals for safe handling of cytotoxic drugs
Drug administration
Waste disposal
Developing standard procedures
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APOPC JAKARTA 2012
DEFINITION OF CT DRUGS
• Genotoxic – damage DNA
• Mutagenic – alter DNA
• Teratogenic – malformation of embryo or fetus
• hazardous to cells
Specific destructive action on cells that may be:
• rheumatoid arthritis
• multiple sclerosis
• auto-immune disorders
Therapeutic agents intended for but not limited to treatment of cancer
Inhibit cell growth by affecting cell cycle resulting in a blockage of cell partition & multiplication.
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DEFINITION OF CT DRUGS
• Cancerous cells
• Cells from the GI tract
• Hair follicles
• Early blood cells in bone marrow
Affect all cells, but more on cells that divide rapidly or uncontrollably
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LONG TERM EFFECTS OF CT DRUGS
Small but significant numbers of patients treated successfully with aggressive cancer chemotherapy later present with secondary malignancies, often AML
More commonly used
MTX & cyclophosphamide
to treat RA, MS & other non-malignant diseases
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Contact dermatitis Cytogenetic abnormalities & mutagenic activity related to biological uptake by exposed personnel Alterations to normal blood cell counts
Excretion of drug or metabolites in urine
Abdominal pain, hair loss, nasal sores & vomiting
Liver damage
Foetal loss & malformations
Guidelines for handling cytotoxic drugs and related waste in health care establishments Work Cover NSW
POTENTIAL EFFECTS OF EXPOSURE
Long term effects of occupational exposure to CT are inconclusive
BUT
not appropriate to wait for indisputable evidence of harm
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SIGNIFICANT REPORTS OF OCCUPATIONAL EXPOSURE TO CT DRUGS: 1979 – 1999
Falck 1979 mutagens in urine of nurses preparing CTX
Neal 1983 CPM & FU aerosols in air of clinics
Hirst 1984 CPM detected in blood of nurses
Selevan 1985 foetal loss in exposed pregnant nurses
Hemminki 1985 defects in offspring of exposed nurses
Saurelle-
Cubizolles
1993 factor in ectopic pregnancies
Sessink 1994 skin contamination a major cause
Valanis 1999 foetal loss, reduced fertility in males, females
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Identify path CT drugs follow from point of entry to exit as
• reconstituted product
• patient waste
• contaminated laundry
• contaminated equipment
Includes:
• receiving
• transportation
• storage
• preparation
• administration
• waste handling
EXPOSURE ASSESSMENT
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WHO IS AT RISK?
Everyone involved in the handling
Manufacturers & shipping
Pharmacists & pharmacy assistants
Physicians & nurses
Housekeeping
Family members & friends
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SOURCES OF CONTAMINATION?
Vials and packaging surface contamination
Leaks/spills
Aerosol generation, spraying, splattering
Excreta of patients
Surface contamination on BSC, carts, tables,
counters, equipment, wards, bedside
•Withdrawing of needles from drug vials
•Use of syringes and needles or filter straws for transfer
•Opening of ampoules
•Expulsion of air from syringe when measuring the
precise volume of drug
Surface contamination
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MANUFACTURER
Some vials have significant cytotoxic drug residue on vial surface – exposure
Plastic coated vials appear safest
Plastic vials also appear safe
Methods of packing for transit to be specified
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Classify & segregate CT drugs
• Areas where drugs are received
• Quarantine packages with visual signs of damage
• Dedicated storage areas
• Use PPE when handling CT drugs
• Wash hands after handling CT drugs
• Spill kit available
• Proper waste disposal of damaged goods & PPEs
Purchase of CT drugs designed to minimise risk of breakage
• unbreakable plastic material
• glass vials provided in specially designed outer plastic containers
• glass vials over-wrapped in plastic
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External transport from supplier
• Primary containers designed to minimise breakage
• use of parenteral grade polypropylene vials, resistant to breakage or reinforced plastic coated vials
• Packed in high impact resistant packaging material made from heavy duty corrugated cardboard & lined with moulded foam to prevent accidental damage to contents
Internal transport of commercial product
Internal transport of compounded admixture
• To prevent damage, pack in a labelled, sealed, leak-proof container, protected from light
• ISOPP Standards of Practice Section 5
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ROUTES OF EXPOSURE
Inhalation of droplets or vapour during preparation or administration
Ingestion – surface contamination/substandard practices
Topical contact – spills or improper/inadequate PPE, conjunctival absorption
Direct injection – needle stick injury
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ROUTES OF EXPOSURE
Vials & packaging in which cytotoxic drugs are stored
Leaks/spills surface contamination on BSC, carts, tables, counters, equipment…etc
Aerosolisation surface contamination on minibags, syringes, pumps
Handling excreta & linen of patients
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INHALATION OF DRUG VAPOUR
Cytotoxic drugs evaporate at 23°C & 37°C
Drug 23°C Drug 37°C
Carmustine ++ Carmustine ++
Nitrogen mustard ++ Cyclophosphamide ++
Cyclophosphamide + Ifosphamide ++
Thiotepa ++
Nitrogen mustard ++
Fluorouracil ? Fluorouracil ?
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Protect & secure packages of CT drugs
Educate & train all involved personnel
During manipulation, use of devices & negative pressure techniques
Eliminate potential for exposure with CT drugs
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•Disposable gown made of non-linting & non absorbent polyethylene-coated polypropylene material Coverall or gown
Head covering
Closed footwear
•double gloving (nitrile, neoprene latex)
• long enough to cover cuffs of gowns or coveralls
•changed every 30 minutes Gloves
Protective eyewear/goggles
Respirator masks
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CT drugs should be handled & stored within the pharmacy by
trained employees
Preparation of parenteral CT drugs should be undertaken only
by trained pharmacy personnel
Reconstituted product should be protected against microbial,
particulate & chemical contamination
Operators should be protected against exposure to hazardous
drugs.
ISOPP Standards of Practice Section 3
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Pharmaceutical analysis & QC implemented
improves quality of preparation
safety of patient is enhanced
Economic benefits
Location:
Commonly – pharmacy
Sometimes - outpatient oncology department or close to inpatient ward
Ease of transport
Enhanced communication between pharmacy, medical & nursing staff
Must be under control of pharmacist
ISOPP Standards of Practice Section 6
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Possess recognized qualification
Received certified training in accordance with local regulations
Assessment of practice undertaken on a regular basis
Staff members should be evaluated on a regular basis to verify compliance with procedures
Strict hygiene must be developed & followed
No eating, drinking, chewing gum & application of cosmetics must be strictly prohibited
No wearing of jewellery
ISOPP Standards of Practice Section 3
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Appropriate staff chosen – good work habits, teachable & fussy
about cleanliness
Personnel must be informed of known & potential hazards of CT
drugs they are handling
Document contents of training & the individual completion of
training
“Worker right to know” regulations
Knowledge of & competence in procedures MUST be tested at the
end of the training
Re-test periodically every 6-12 months
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Potential risks to exposure to CT agents
Basic pharmacology of CT agents
Theory of aseptic technique
Use of PPE
Theory of containment devices & barriers
Theory of hierarchy of protection measures
Handling of CT waste
CT spills & accidental exposure
Prescribing of CT agents
Validation of CT prescriptions
Hospital policies & procedures on CT management
CT drug use processes drug selection
prescription validation
preparation
dispensing
drug administration & drug use evaluation
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ISOPP Standards of Practice Section 4 APOPC JAKARTA 2012
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Each institution should develop & maintain a procedure
manual, detailing:
policies & procedures for appropriate manufacture &
administration of CT drugs
aseptic techniques
SOPs for reconstitution & administration
cleaning procedures
spill management
transporting CT drugs
health monitoring
ISOPP Standards of Practice Section 4
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A training program in CT reconstitution should be developed
& implemented
Can be offered in-house or by an external training provider
Training should be:
tailored to specific needs of the individual
ongoing with regular updates & information for any new
procedures or products e.g. new hazardous drug introduced at
workplace
Include periodic tests of staff competencies
Structured program which contains important elements
ISOPP Standards of Practice Section 4
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Validation of processes to demonstrate processes used during & staff undertaking aseptic
manipulation are capable of maintaining sterility of product
media fill test is intended to simulate routine aseptic operations
Validation of operator to demonstrate aseptic technique of operator is capable of maintaining
sterility
ensure operators do not contaminate themselves
Validation of training ensure all staff have a satisfactory level of knowledge & competency
Evaluation On-going feedback should be an integral part of the program
Re-training Repeated every 2-3 years
ISOPP Standards of Practice Section 4
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Need to ensure protection of product
Aseptic techniques
Microbial contamination
Chemical contamination
Centralised service
Dedicated facilities
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Protect handler of vial/ampoule
Vials enclosed in plastic coating
Protect operator during preparation
Closed system in regards to microbiological & chemical
contamination (leakproof, airtight device)
Protect administrator during administration of CT
drug
Techniques to protect patient
ISOPP Standards of Practice Section 7
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DRUG PREPARATION WITH CLOSED SYSTEMS
Slide courtesy of Thomas Connor ISOPP VIII Vancouver APOPC JAKARTA 2012 50
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Administered mainly by nurses
Exposure due to surface contamination of products made by pharmacy, connection/disconnection during administration including oral products using oral liquid dispensing syringes
Use PPEs when administering
Remove IV bag intact or use contained systems
Flushing
Wash hands after administration
Closed systems
Excreta of patient as second dilution of drug
Spill management
Proper disposal of CT waste
ISOPP Standards of Practice Section 12
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Double checking for correct
patient, route, dose &
regime
Swabbing rubber bung Administering bolus doses
Setting up the infusion Commencing administration
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Do cut or crush tablets
Use gloves when handling oral CT drugs
Do not open capsules
If necessary, dissolve in warm water
Return excess drugs to pharmacy
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Leak proof & puncture proof sharps containers
Sharps container no more than ¾ full
Waste tied up & removed after each shift
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Waste bags made of
polyethylene or
polypropylene, purple in
colour
Segregated, packaged &
disposed properly
Use of dedicated
hardwalled carts
Undertake waste
collection frequently
Incineration at 1100°C
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Staff
health monitoring
exposure to CTs
education & training
validation
Facilities
microbiological & contamination monitoring
maintenance log
pressure differentials
temperature logs
particle counts
qualification & re-qualification
ISOPP Standards of Practice Section 21
Training file for each personnel!
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Transport
Outside & within the institution
Cytotoxic spills
Extravasation
Cleaning
BSC/isolator
Sterile room
Workload statistics
Procedure manual
Material safety data sheet (MSDS)
ISOPP Standards of Practice Section 21
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CONTROL MEASURES
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Key risk controls include:
• Outsourcing CT drug preparation work
• Purchasing CT drugs in the safest form available
• Reviewing health & safety information about CT drugs
• Using facilities that meet recommended technical & safety standards
• Designing & laying out work area according to recommended standards
• Adopting closed system operations
• Providing employees with information & training
• Automation
Guidelines for handling cytotoxic drugs and related waste in health care establishments WorkCover NSW
APOPC JAKARTA 2012
SAFETY IN HANDLING CT DRUGS
•Policies & procedures
• Minimum standards, ISOPP standards
• Root cause analysis for spills & needle stick injuries
• Maintain records
• Health surveillance
• Training & validation
• Retraining
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ISOPP Standards of Practice J Oncol Pharm Practice (2007)
Supplement to 13: 1-81
Guidelines for handling cytotoxic drugs and related waste in health
care establishments WorkCover New South Wales
NIOSH Alert: Preventing occupational exposures to antineoplastic &
other hazardous drugs in health care settings 2004
ASHP Guidelines on Handling Hazardous Drugs Am J Health-Sys
Pharm. 2006;1172-93
REFERENCES
APOPC JAKARTA 2012