1. Managing Waste Chemotherapeutic Agents: What to Know and What to Find Out H2E Teleconference March 11, 2005 Eydie Pines eydie.pines@h2e-online.org Charlotte Smith csmith@pharmecology.com

2. Know the Lingo Cytotoxic Cytotoxic Antineoplastic Antineoplastic Chemotherapeutic Chemotherapeutic Biohazardous Biohazardous Refers to infectious waste, Blood Borne Pathogens ActRefers to infectious waste, Blood Borne Pathogens Act In Pharmacy circles, often used to refer to agents which are hazardous to living systems, such as chemotherapy drugsIn Pharmacy circles, often used to refer to agents which are hazardous to living systems, such as chemotherapy drugs Need to correct this misconception and use the term only for infectious wasteNeed to correct this misconception and use the term only for infectious waste

3. Chemotherapeutic Agents: The Regulatory Players OSHA Hazard Communication Standard OSHA Hazard Communication Standard OSHA Technical Manual Section 6, Chapter 2, Appendix VI: 2- 1OSHA Technical Manual Section 6, Chapter 2, Appendix VI: 2- 1 Lists hazardous drugsLists hazardous drugs NIOSH Hazardous Drug Alert NIOSH Hazardous Drug Alert Recently released comprehensive new guidelines for total life cycle management of OSHA “Hazardous Drug”Recently released comprehensive new guidelines for total life cycle management of OSHA “Hazardous Drug” Identifies “hazardous waste” and need for appropriate disposalIdentifies “hazardous waste” and need for appropriate disposal EPA RCRA EPA RCRA Only 9 chemotherapy drugs “listed” as hazardous waste in 1976Only 9 chemotherapy drugs “listed” as hazardous waste in 1976 None added to the list to keep up with drug developmentNone added to the list to keep up with drug development State RMW Regulations State RMW Regulations May include trace chemotherapyMay include trace chemotherapy Treated as infectious medical waste through regulated medical waste incineration Treated as infectious medical waste through regulated medical waste incineration

4. NIOSH Hazardous Drug Alert Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare SettingPreventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Setting Recognizes risks to employeesRecognizes risks to employees Recommends engineering controls, administrative controls, and personal protective equipmentRecommends engineering controls, administrative controls, and personal protective equipment Provides waste disposal guidelinesProvides waste disposal guidelines http://www.cdc.gov/niosh/docs/2004-165/http://www.cdc.gov/niosh/docs/2004-165/http://www.cdc.gov/niosh/docs/2004-165/ Appendix A provides a starting list of hazardous drugs under OSHA (not to be confused with hazardous waste under EPA)Appendix A provides a starting list of hazardous drugs under OSHA (not to be confused with hazardous waste under EPA)

5. Chemotherapeutic Drugs: Here, There and Everywhere 75% of pharmacy areas and 65% of administration areas demonstrated some level of contamination 75% of pharmacy areas and 65% of administration areas demonstrated some level of contamination Contamination was generally higher in the pharmacy than in the administration areas Contamination was generally higher in the pharmacy than in the administration areas Locations adjacent to handling areas were also contaminated. Locations adjacent to handling areas were also contaminated. Conner TH, Anderson RW, Surface contamination with antineoplastic agents in six cancer center treatment centers in Canada and the United States. AMJ Health-System Pharm 1999: 56- 1427-32. Conner TH, Anderson RW, Surface contamination with antineoplastic agents in six cancer center treatment centers in Canada and the United States. AMJ Health-System Pharm 1999: 56- 1427-32.

6. New Study Reveals Chemotherapy on Vials Documents external contamination on vials from manufacturers Documents external contamination on vials from manufacturers Supports requiring personnel who check in or handle chemotherapy containers to wear appropriate personal protective equipment Supports requiring personnel who check in or handle chemotherapy containers to wear appropriate personal protective equipment Conner TH, Sessink JM et al, Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: Results of three studies. AMJ- Health-System Pharm 2005: 62-475-84 Conner TH, Sessink JM et al, Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: Results of three studies. AMJ- Health-System Pharm 2005: 62-475-84

7. Beyond the Obvious: Where Chemo Wastes are Generated Operating Room Operating Room Mitomycin eye drops, bladder irrigant (U listed)Mitomycin eye drops, bladder irrigant (U listed) Med-Surg Floors Med-Surg Floors Immunosuppressives, eg. Rheumatoid arthritisImmunosuppressives, eg. Rheumatoid arthritis Methotrexate (Not listed) Methotrexate (Not listed) Cyclophosphamide (U listed) Cyclophosphamide (U listed) Emergency Department Emergency Department Ectopic pregnancyEctopic pregnancy Methotrexate Methotrexate

8. Examples of Chemotherapy Dosage Forms Tablets/Capsule Tablets/Capsule Chlor-am'-bu-cil, U035 Leukeran®Chlor-am'-bu-cil, U035 Leukeran® Vial – Powder Vial – Powder Cyclophosphamide U058Cyclophosphamide U058 Cy-clo-phos´-pha-mide, Cytoxan®, Neosar® Cy-clo-phos´-pha-mide, Cytoxan®, Neosar® Melphalan U150Melphalan U150 Mel´-phal-an, Alkeran® Mel´-phal-an, Alkeran® Vial – Liquid Vial – Liquid Fluorouracil (Not listed)Fluorouracil (Not listed) Fluor-o-ur’-a-cil, 5FU, Adrucil® Fluor-o-ur’-a-cil, 5FU, Adrucil® Ampule – Liquid Ampule – Liquid Arsenic Trioxide P012Arsenic Trioxide P012 Trisenox® Trisenox®

9. The Dispensing Instrument Matters Syringes Syringes EPA Hotline guidance exempts epinephrine syringe that has been injected into a patient and is therefore infectious waste; exclusion was extended verbally to other P and U listed drugs in a used syringe – open to interpretationEPA Hotline guidance exempts epinephrine syringe that has been injected into a patient and is therefore infectious waste; exclusion was extended verbally to other P and U listed drugs in a used syringe – open to interpretation IV Sets IV Sets IV bags that are not empty and can be separated from patient exposed sharp without exposing the employee should be managed as RCRA hazardous wasteIV bags that are not empty and can be separated from patient exposed sharp without exposing the employee should be managed as RCRA hazardous waste IV bags that are not empty and can NOT be separated from patient exposed sharp without exposing the employee should be managed as both RCRA hazardous waste and RMWIV bags that are not empty and can NOT be separated from patient exposed sharp without exposing the employee should be managed as both RCRA hazardous waste and RMW Vials Vials Vials that are not empty should be managed as RCRA hazardous wasteVials that are not empty should be managed as RCRA hazardous waste Tablets Tablets Unused tablets should be managed as RCRA hazardous wasteUnused tablets should be managed as RCRA hazardous waste

10. Arsenic Trioxide: The Only P-Listed Chemo Waste Consider all containers that have held arsenic trioxide to be hazardous waste Consider all containers that have held arsenic trioxide to be hazardous waste RCRA empty for P-listed drugs requires triple rinsing of the container – not practicalRCRA empty for P-listed drugs requires triple rinsing of the container – not practical Over 1 kg (2.2 lbs) of P waste in a calendar month results in large quantity generator status Over 1 kg (2.2 lbs) of P waste in a calendar month results in large quantity generator status Weights of P-listed drug waste must be combined with any other P-listed waste generated at the facility in a given month Weights of P-listed drug waste must be combined with any other P-listed waste generated at the facility in a given month If an IV set containing P-listed wastes is also considered infectious waste, it may have to be managed by a facility permitted to handle both hazardous waste and RMW If an IV set containing P-listed wastes is also considered infectious waste, it may have to be managed by a facility permitted to handle both hazardous waste and RMW

11. Chemotherapy Agents: Many Are Not Regulated by RCRA Over 100 chemotherapy agents not regulated by EPA Over 100 chemotherapy agents not regulated by EPA Examples: Examples: Alkylating agents: Cisplatin, ThiotepaAlkylating agents: Cisplatin, Thiotepa Antimetabolites: Fluorouracil, MethotrexateAntimetabolites: Fluorouracil, Methotrexate Hormonal (antiandrogen): Lupron® (leuprolide)Hormonal (antiandrogen): Lupron® (leuprolide) Hormonal (antiestrogen): TamoxifenHormonal (antiestrogen): Tamoxifen Mitotic Inhibitor: Taxol® (paclitaxol)Mitotic Inhibitor: Taxol® (paclitaxol)

12. Some Chemotherapy Drugs May Also Be Ignitable Aqueous Solution containing 24% alcohol or more by volume & flash point<140° F. Aqueous Solution containing 24% alcohol or more by volume & flash point<140° F. Hazardous Waste Number: D001 Hazardous Waste Number: D001 Example: Paclitaxel Inj contains 49.7% ethanol Example: Paclitaxel Inj contains 49.7% ethanol Dispose in ignitable container Dispose in ignitable container

13. Trace Chemotherapeutic Waste A term used to define items which are RCRA empty but which have held any chemotherapy or been potentially exposed to chemotherapy A term used to define items which are RCRA empty but which have held any chemotherapy or been potentially exposed to chemotherapy To avoid autoclaving or microwaving of items which may be contaminated at the molecular level with undetected chemotherapy To avoid autoclaving or microwaving of items which may be contaminated at the molecular level with undetected chemotherapy Requires incineration at an RMW incinerator; may be infectious such as used needles Requires incineration at an RMW incinerator; may be infectious such as used needles IV tubes primed with saline by the pharmacy and flushed with saline before being removed from patient can be managed as trace chemotherapeutic waste, reducing the volume of hazardous waste generated, reducing contamination of PPE, and lessening employee exposure IV tubes primed with saline by the pharmacy and flushed with saline before being removed from patient can be managed as trace chemotherapeutic waste, reducing the volume of hazardous waste generated, reducing contamination of PPE, and lessening employee exposure

14. Discarding Contaminated Personal Protective Equipment and Spill Clean Up Material Personal Protective Equipment (PPE) and spill clean up material contaminated with P- or U-listed waste must be managed as hazardous waste Personal Protective Equipment (PPE) and spill clean up material contaminated with P- or U-listed waste must be managed as hazardous waste

15. Empty vials, syringes, IVs, tubing, gowns, gloves,etc. Bulk chemo in vials, unused IV’s, P, U, toxic D and associated spill clean up materials Traditional Trace Chemo Waste Containers New Hazardous Waste Containers Hospitec Kendall DOT approved

16. Treatment Technologies: Regulated Medical (Infectious) Waste Incinerators Permitted by the state to accept pathology waste, infectious waste and sharps, trace chemo waste Permitted by the state to accept pathology waste, infectious waste and sharps, trace chemo waste Regulated under the Clean Air Act Regulated under the Clean Air Act Lower temperature, less controls than RCRA permitted hazardous waste incinerators Lower temperature, less controls than RCRA permitted hazardous waste incinerators Ash disposed of in a municipal (non- hazardous) landfill Ash disposed of in a municipal (non- hazardous) landfill

17. Characteristic and Listed Hazardous Waste: Toxic P,U,D hazardous RX (non-chemo) Bulk chemo vials, IV bags Chemo and haz spill materials Investigational drugs Regulation: Acronym: Contents: Treatment: Purpose: Resource Conservation & Recovery Act RCRA Toxic Hazardous Waste Incineration at a RCRA hazardous waste incinerator Destroy chemical compound entirely Final Disposition: Lined hazardous waste landfill

18. Characteristic Hazardous Waste: Ignitable D001 Ignitable hazardous RX Regulation: Acronym: Contents: Treatment: Purpose: Resource Conservation & Recovery Act RCRA Ignitable Hazardous Waste Incineration at a RCRA hazardous waste incinerator Destroy chemical compound entirely Final Disposition: Lined hazardous waste landfill

19. Treatment Technologies: Hazardous Waste Incinerators Permitted by USEPA, known as a Treatment, Storage and Disposal Facility (TSDF) Permitted by USEPA, known as a Treatment, Storage and Disposal Facility (TSDF) High temperature, molecular bonds broken High temperature, molecular bonds broken Pollutants scrubbed, emits only water vapor, ash stored in a lined, hazardous waste landfill Pollutants scrubbed, emits only water vapor, ash stored in a lined, hazardous waste landfill Authorized to accept the “worst of the worst” hazardous chemicals, shipped on a 5-part manifest Authorized to accept the “worst of the worst” hazardous chemicals, shipped on a 5-part manifest Examples: Examples: Clean Harbors/Safety KleenClean Harbors/Safety Kleen HeritageHeritage OnyxOnyx TerisTeris

20. Combination Wastes: Infectious and Hazardous If IV bag chemo drug has been hung, is not completely used and can be separated from patient exposed sharp or catheter without exposing the employee, remove and incinerate IV set as RCRA hazardous waste If IV bag chemo drug has been hung, is not completely used and can be separated from patient exposed sharp or catheter without exposing the employee, remove and incinerate IV set as RCRA hazardous waste If chemo residue cannot be removed safely, states differ on regulatory requirements If chemo residue cannot be removed safely, states differ on regulatory requirements Florida – may dispose as biohazardous, infectious wasteFlorida – may dispose as biohazardous, infectious waste Minnesota – must dispose as hazardous waste; may be considered infectiousMinnesota – must dispose as hazardous waste; may be considered infectious Engineering controls are making this scenario less frequent Engineering controls are making this scenario less frequent Clean Harbors is permitted to incinerate combination wastes at their RCRA/RMW facility in Deer Park, Texas and Aragonite, Utah Clean Harbors is permitted to incinerate combination wastes at their RCRA/RMW facility in Deer Park, Texas and Aragonite, Utah P-listed Arsenic Trioxide is likely to be both a hazardous and infectious waste P-listed Arsenic Trioxide is likely to be both a hazardous and infectious waste

21. Satellite Accumulation At the point of generation At the point of generation Need only a Hazardous Waste (Toxic) or (Ignitable) label Need only a Hazardous Waste (Toxic) or (Ignitable) label May need signage indicating it is Satellite Accumulation based on state requirements May need signage indicating it is Satellite Accumulation based on state requirements Need to keep covered when not in use Need to keep covered when not in use Can accumulate up to 1 quart of P listed waste; 55 gallons of U and mixed waste Can accumulate up to 1 quart of P listed waste; 55 gallons of U and mixed waste Have 3 days to move when limit is reached Have 3 days to move when limit is reached No other time limit involved No other time limit involved

22. Storage Accumulation Hazardous Waste Storage Accumulation Site Hazardous Waste Storage Accumulation Site Same locked area as mercury, xylene, formaldehyde, lab chemicalsSame locked area as mercury, xylene, formaldehyde, lab chemicals Maximum storage time: 90 or 180 days based on generator statusMaximum storage time: 90 or 180 days based on generator status Additional regulatory requirementsAdditional regulatory requirements Hazardous Waste Label

23. Storage Capacity and Location Does your existing hazardous waste storage facility have sufficient capacity for the chemotherapeutic waste stream and other hazardous drug waste? Does your existing hazardous waste storage facility have sufficient capacity for the chemotherapeutic waste stream and other hazardous drug waste? Is the storage accumulation area well removed from patient traffic areas? Is the storage accumulation area well removed from patient traffic areas? Consider how waste will be transported from point of generation to storage accumulation area Consider how waste will be transported from point of generation to storage accumulation area

24. Manifesting Toxic Chemotherapeutic Wastes Approach # 1 Approach # 1 Document all listed P and U drugs that may be used in the organizationDocument all listed P and U drugs that may be used in the organization Have this list pre-certified by the waste vendor as a bulk shipment, rather than a lab packHave this list pre-certified by the waste vendor as a bulk shipment, rather than a lab pack List all waste codes on the manifest regardless of contentsList all waste codes on the manifest regardless of contents Approach #2 Approach #2 Document exactly which P and U listed drugs are deposited in a particular containerDocument exactly which P and U listed drugs are deposited in a particular container List only those waste codes on the manifestList only those waste codes on the manifest Very time consuming, but required in Minnesota in particularVery time consuming, but required in Minnesota in particular

25. Manifesting Ignitable Chemotherapeutic Wastes Segregated into RCRA Ignitable waste container Segregated into RCRA Ignitable waste container May combine with other ignitable drug wastes May combine with other ignitable drug wastes Manifest using the D001 code for ignitability Manifest using the D001 code for ignitability If a P or U listed drug is involved, list the waste code in the shipping name along with the proper DOT ignitable shipping name If a P or U listed drug is involved, list the waste code in the shipping name along with the proper DOT ignitable shipping name

26. Federal Waste Generator Status Large Quantity Generator (LQG): generates more than 1000 kg/month of hazardous waste or >1 kg/month “P” listed waste. Large Quantity Generator (LQG): generates more than 1000 kg/month of hazardous waste or >1 kg/month “P” listed waste. Small Quantity Generator (SQG):Generates 100 kg/month of hazardous waste & 100 kg/month of hazardous waste & < or = 1 kg/month “P” listed waste. Conditionally Exempt Small Quantity Generator (CESQG):Generates < or = 100 kg haz waste/month, < or = 1kg P listed waste/month Conditionally Exempt Small Quantity Generator (CESQG):Generates < or = 100 kg haz waste/month, < or = 1kg P listed waste/month

27. OSHA HAZWOPER* Training Requirements If not Large Quantity Generator, general awareness training and specific work training sufficient If not Large Quantity Generator, general awareness training and specific work training sufficient For Large Quantity Generator, need appropriate levels of HAZWOPER training for employees handling and transporting hazardous waste For Large Quantity Generator, need appropriate levels of HAZWOPER training for employees handling and transporting hazardous waste http://www.osha.gov/pls/oshaweb/owadis p.show_document?p_table=STANDARDS& p_id=9765 http://www.osha.gov/pls/oshaweb/owadis p.show_document?p_table=STANDARDS& p_id=9765 *Hazardous Waste Operations and Emergency Response 1920.120

28. Discovering Waste Minimization Opportunities Is the pharmacy disposing of opened chemo drugs before the expiration date? Is the pharmacy disposing of opened chemo drugs before the expiration date? Is the pharmacy priming the IV tube with saline? Is the pharmacy priming the IV tube with saline? Does the nursing staff flush the IV tube with saline before it is removed from the patient? Does the nursing staff flush the IV tube with saline before it is removed from the patient?

29. Questions for Nursing, Pharmacy and Housekeeping Staff How often are IV bags partially used?How often are IV bags partially used? Do the IV bags have sharps or catheters attached?Do the IV bags have sharps or catheters attached? Are the IV tubes primed with saline by the pharmacy?Are the IV tubes primed with saline by the pharmacy? Are the IV tubes flushed with saline before being removed from the patient?Are the IV tubes flushed with saline before being removed from the patient? How often are gowns changed?How often are gowns changed? How many trace chemotherapy containers are currently being generated?How many trace chemotherapy containers are currently being generated? Are opened vials of chemotherapeutic agents disposed of prior to their expiration date?Are opened vials of chemotherapeutic agents disposed of prior to their expiration date? How often are opened expired chemotherapeutic drugs discarded?How often are opened expired chemotherapeutic drugs discarded?

30. Managing to the Highest Standard Treat all bulk chemotherapy waste (greater than trace amounts) as RCRA hazardous waste Treat all bulk chemotherapy waste (greater than trace amounts) as RCRA hazardous waste Easier to implement – no lists or sorting requiredEasier to implement – no lists or sorting required The right thing to do for human health and the environmentThe right thing to do for human health and the environment Complies with the RCRA statutory definition of hazardous wasteComplies with the RCRA statutory definition of hazardous waste

31. References www.pharmecology.com www.pharmecology.com www.pharmecology.com Pharmaceutical Waste: http://www.h2e- online.org/tools/chem-pharm.htm Pharmaceutical Waste: http://www.h2e- online.org/tools/chem-pharm.htmhttp://www.h2e- online.org/tools/chem-pharm.htmhttp://www.h2e- online.org/tools/chem-pharm.htm RCRA On-Line http://www.epa.gov/rcraonline/ RCRA On-Line http://www.epa.gov/rcraonline/http://www.epa.gov/rcraonline/ NIOSH Hazardous Drug Alert: http://www.cdc.gov/niosh/docs/2004-165/ NIOSH Hazardous Drug Alert: http://www.cdc.gov/niosh/docs/2004-165/ Pharmaceuticals and Personal Care Products as Environmental Pollutants: http://www.epa.gov/nerlesd1/chemistry/pharma/index. htm Pharmaceuticals and Personal Care Products as Environmental Pollutants: http://www.epa.gov/nerlesd1/chemistry/pharma/index. htm http://www.epa.gov/nerlesd1/chemistry/pharma/index. htm http://www.epa.gov/nerlesd1/chemistry/pharma/index. htm Containers Containers Hospitec: Christopher Hahn, (561) 833-2296, chris@hospitecinc.comHospitec: Christopher Hahn, (561) 833-2296, chris@hospitecinc.com chris@hospitecinc.com Kendall: Mike Liscio, (508) 261-8493, mike.liscio@tycohealthcare.comKendall: Mike Liscio, (508) 261-8493, mike.liscio@tycohealthcare.com