1. Safe handling of cytotoxic drugs and cytotoxic waste
General ideas about types and hazards
of cytotoxic drugs and cytotoxic waste
Safe handling, storage, transportation
Accidents and spillages
Disposal of cytotoxic waste

2. Types and Hazards of CMR‘s
Cytotoxic drugs
= antineoplastic agents
Antiviral drugs
GENOTOXICITY
Carcinogenic
Mutagenic
Reproductive toxicity T
ACUTE TOXICITY
LOCAL TOXICITY
Vesiccant
irritant

3. Types and hazards of cmr‘s
 120 antineoplastic agents in the EEC market
 50 intravenous
antineoplastic agents
routinely used
Supplied as:
Solutions in Ampoules
Powder in glass or plastic vials
Solutions
in glass vials
in plastic bags
plastic vials
Special protected items (new)

4. Precautions in Different Toxicity Classes ?
Precautions to Handling during preparation and disposal according to the type and nature of the risk
Eg Protective Clothing:
1. Long-sleeved shirt
2. Gloves (dermaprene)
3. Rubber clogs or overshoes
4. Cap
5. Mask (optional)

5. Precautions at pharmacy
Avoid occupational exposure to cytotoxics
Centralized cytotoxics preparation area, Safety cabinet
Always two persons working
Protective clothing
Gloves, clothes, overshoes, cap, (mask)
Separate waste collection in leak-proof black containers
and labelling for identification
Safe storage
Ensure high safety standards
Written procedures
Safety data sheets
Procedures for accidents and spillages
Education and training
Zeigen: Pacto-Safe Broschür,

6. Sources of occupational exposure and cytotoxic waste at Pharmacy Site
Surface contamination of the drug by manufacturing processes
Contamination of the packages due to accidents during transportation from supplier to pharmacy
Contaminated materials due to preparation
Spillage on transportation to the wards
Contaminated materials due to administration
Contamination due to storage and disposal

7. Example : Augsburg Cytotoxic Drugs Reconstitution Service
1 Pharmacist
5 Assistents
preparations
a year ( 140 / day)
50% Bolus injections
50% Infusion solution
computer checking of the prescriptions

8. Topics around cytotoxic service
Cytotoxics order separately from other drug orders
separate storage places in pharmacy
Highly sophisticated preparation techniques by specially trained personnel
Safety Guidelines
Waste management Procedures

9. Separate ordering and shipment
Cytotoxics delivery
Confirming shipment documents

10. On-site Transportation and storage
transportation separated from other drugs
Storage: preparation area

11. Safe handling during preparation
Important : Trained personnel
class II safety cabinets in clean room

12. Protecting the preparations
Sealing the preparations
Sealed infusion solution
and bolus injection

13. Transportation from pharmacy to wards
well closed and signed boxes

14. Sorting waste at oncology wards
1. Non hazardous waste

15. Cytotoxic waste segregation at wards
trace contaminated waste
“empty“ items and items have been used during application
cytotoxic waste
( bulk contaminated waste ) ( items that have not been used )
Hazardous Waste
from Cytotoxic
preparations

16. Sorting waste at oncology wards
2. Segregating Hazardous Waste
Trace
Contaminated
cytotoxic
waste
Coloured box:
empty syringes
empty infusion solutions
Flushed Infusion lines
Gloves,
masks

17. Sorting waste at oncology wards
Bulk
Contaminated
„Cytotoxic“
waste
2. Bulk contaminated Hazardous Waste
Coloured box :
Not administered preparations in syringes or infusion bags
Accidentially perforated infusion bags prior to administration
Accidents during storage or transportation

18. Sorting normal waste at pharmacy reconstitution unit
Plastics
Papers
General waste
Glass bottles
(beyond hoods)
General waste

19. Segregation of Cytotoxic waste at reconstitution unit
trace contaminated waste
“empty“ items and items have been used during preparation inside hood
cytotoxic waste
( bulk contaminated waste ) ( USA: > 3% drug remaining in vial )
Waste from Cytotoxics
preparation

20. Treatment of trace contaminated waste from inside hoods
Empty vials / ampoules
Used compresses
Used syringes
Used gloves
Used cannulas
Used mats
Used trays

21. Disposing trace contaminated waste from inside hoods
Example : Double packaging into grey box using pacto-safe ™

22. Treatment of Cytotoxic waste generated inside the hoods
Rigid box being inside the hood
Cytotoxic waste:
expired cytotoxic drugs
Residual drug solutions
Filled syringes

23. Treatment of cytotoxic waste from inside hoods
Double packaging
into black box
By a second pacto-safe ™

24. Treatment of cytotoxic drug spillage
Appropriate protective clothing
Spill kit in the pharmacy

25. Treatment of cytotoxic waste
From inside hoods
„White box“ cytotoxic waste
spillages
From wards
Bulk contaminated cytotoxic waste back from wards
Leakages
Not used but expired preparations
From supplier
contaminated vials do to manufacturer
Damaged small or large amounts during transportation from manufacturer to pharmacy

26. Bulk contaminated Cytotoxic waste back from the wards to pharmacy
Tightly closed
Brought, not sent !!
Document filled out by the waste generator

27. Example of Transporting waste to central storage
Cytotoxic waste
Trace contaminated waste,
papers
plastics

28. Cytotoxic waste disposal options
Back to supplier !?
Chemical destruction
small amounts of solids and semi-solids, powders
glassware
aqueous solutions ( ampoules, vials
injectable pharmaceutical preparations
spills - solid compounds
- aq. solutions and pharmaceutical preparations

29. WHO recommended chemical destruction methods for cytotoxic drugs
commonly used reagents: Drugs
H2SO4, KMnO VCR, VBL, 6-TG, 6-MP, Procarbacin
NaOH /KMnO MTX
HCl/ Na2S2O CTX
Zn/H2SO4 or Al/HCl Cisplatin, Carboplatin
NaOH/DMF CTX, IFO
NaOCl MTX
Neutralisation:
Na2S2O3, NaOH, Ascorbic Acid
Examples

30. Chemical destruction methods for cytotoxic drugs
Apparatus:
high quality standard laboratory equipment
Methods: magnetic stirring or refluxing
Surrounding: safety cabinet
1.Well founded chemical knowledge
2. in hospitals only at pharmacy
3. residual solutions
must be free from
remaining
mutagenicity

31. Chemical destruction methods for cytotoxic drugs
NaOCl 5,25% H2O2 30% Fentons Reagent
or 15% (Fe-II-Cl2 3% in H2O2 30%)
Easily peformable
Reaction : 10ml Prepn ml Reagent in an Erlenmeyer flask
for 1-3 hrs at room temp.
then
Neutralisation ( ice-bath) with Na2SO3 and 12M-HCl.
In case of Fentons Reagent: take Erleneyer flask with 5 times
the Preparation/Reagent-Volume.
Int.Arch Occup Environ Health (1997) 69:

32. Chemical destruction methods for cytotoxic drugs ( cont.)
Treatment of spillages – policies ???
For example
Isolate the area
Spillage warning
Get spill kit
Whipe up spilled liquids with dry cellulose
( In case of spilled powders first cover spillage
with wet cellulose.
Then whipe up stamp spillage with dry cellulose)
Rinse area with NaOCl 5% for 1 hour
Whipe up with dry cellulose
Repeat step 6 and 7
Clean area with water and detergents

33. cytotoxic waste disposal options
Back to supplier
Chemical destruction
Immobilisation
High temperature Incineration
a) regional policies
b) Special
authorization:
1000 – 1200 oC
Amsacrin
Cisplatin
Dacarbazin 500
Melphalan
Anthracyclines ca 800

34. Final disposal of trace contaminated „cytotoxic“ waste
High risk double lined landfill
High temperature Incineration

35. Final disposal methods for cytotoxic waste answered questions by different countries
country
definition
Disposal method
Belgium
( Centre Hospitalier New Paul Brien, Brussels
Bottles, cannulas, syringes, clothes, compresses
„Special waste“ UK
(Queens Medical Centre Nottingham)
Cytotoxic residues incl. Empty syringes or bags, all trace contaminated material as well as sharps
High temperature incineration
Netherlands
(Akad. Ziekenhuis Utrecht)
Cytotoxics and all materials having contact with
Austria
( ÖNORM S 2104)
Cytotoxics in higher concentration
Contaminated materials like
Gloves, infusion lines, gauzes, compresses
Dangerous waste
Must not be disposed according to dangerous waste disposal

36. Final disposal methods for cytotoxic waste answered questions by different countries
country
definition
disposal method
Sweden
(Federation of swedish county councils)
Residual Cytotoxics and all materials been in contact with; urine and excrement containing
Municipal waste incineration
Switzerland
(Basel Hospital )
Unused/expired Cytotoxics,
Residuals, and all materials been in contact with
USA
( NIH recommendation)
Trace contamin. Waste (<3%)
Bulk contamin. Waste(>3%)
Clinic based incineration
Special authorized incineration facility

37. Final disposal methods for cytotoxic waste answered questions by some german hospitals
definition
Disposal method
Freiburg
Residual Cytotoxics from peparation > 20ml, stock solutions
All materials had contact with cytotoxic drugs
„Incineration“
Augsburg
all „trace contaminated materials“ = all materials used during preparation or application.
Unused/expired Cytotoxics and any residuals from preparations
Municipal waste incineration
(AVA)
high temp. incineration by special authorized facility

38. Not recommended final disposal methods for cytotoxic waste
STOP
Sewer
Fast flowing water course
open uncontrolled dump or landfill.
Burning in open containers