Transcript Update on Safe Handling of Hazardous Drugs

Update on Safe Handling of
Hazardous Drugs:
Stakeholder Activities
Melissa A. McDiarmid, MD, MPH
August 1, 2002
ASHP Hazardous Drug Criteria
1. Genotoxicity (i.e., mutagenicity and clastogenicity in short-term test systems)
2. Carcinogenicity in animal models, in the patient
population, or both as reported by IARC
3. Teratogenicity or fertility impairment in animal
studies or in treated patients
4. Evidence of serious organ or other toxicity at low
doses in animal models or treated patients.
Historical Background
Mustard gas development
WWI
Alkylating agents used clinically
1940's
Regular part of cancer treatment
1960's
Second malignancies reported
1970's
Developmental Toxicity and Genotoxicity of
Some Common Anticancer Agents
Drug Class
Alkylating Agents
BCNU
Busulfan
Chlorambucil
Cyclophosphamide
Ifosfamide
Nitrogen Mustard
Thiotepa
Cis-diaminedichloroplatinum
Antibiotics
Actinomycin
Adriamycin
Bleomycin
Daunomycin
Developmental Toxicity
Animal
T
E
Human
Genotoxicity
PM
CE
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
(+) = effect seen; (-) = no effect seen. (T)=Teratogenic; (E)=Embryotoxic, (PM)=Point Mutation,
(CE)=Chromosomal Effects
Developmental Toxicity and Genotoxicity of
Some Common Anticancer Agents
Drug Class
Antimetabolites
Cytosine arabinoside
5-Fluorouracil
6-Mercaptopurine
Methotrexate
Mitotic Function
Vincristine
Vinblastine
Taxol
Miscellaneous
DTIC (Dacarbazine)
Procarbazine
Topoisomerase II Function
Etoposide*
Developmental Toxicity
Animal
T
E
Human
Genotoxicity
PM
CE
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
±
+
+
+
+
-
+
+
+
+
(+) = effect seen; (-) = no effect seen. (T)=Teratogenic; (E)=Embryotoxic, (PM)=Point Mutation, (CE)=Chromosomal Effects
*Data summarized from Sorsa M, Hemminki K, Vainio H. Occupational exposure to anticancer drugs: potential and real
hazards. Mutat Res 1985;154:135-149. Updated by McDiarmid, MA. Antineoplastics, Anesthetic Agents, Sex Steroid
Hormones in Paul, M Occupational and Environmental Reproductive Hazards, 1993.
Severity of the Hazard
Hazardous Drugs are:
• 11 of 70-odd IARC Group I Carcinogens
• 8 of Group 2A; and 7 of Group 2B
• Well documented reproductive and
developmental toxicants in animals and
humans (Alkylating Agents,
Antimetabolites); some male-mediated
• Associated with biologically plausible
health effects in studies of exposed
populations
SUMMARY OF STUDIES OF ADVERSE REPRODUCTIVE OUTCOMES IN
WORKERS EXPOSED TO ANTINEOPLASTIC DRUGS
OUTCOME
Year
Author
Population
Birth
Defect
Fetal
Loss
1985
Hemminki
Onc Nurses
*
-
1985
Selevan
Onc Nurses
*
1986
Taskinen
Pharm Mfgr.
+
1987
Rogers
Onc Nurses
*
1988(a) McDonald
RNs + MDs
1988(b) McDonald
RNs + MDs
-
1990
Onc Nurses
*
Stucker
Other
*
Key: (+) = effect seen, (-) = no effect seen, (*) = statistically significant effect seen
(F) = female; (M) = male; (LBW) = low birth wt; (SGA) = small for gestational age.
SUMMARY OF STUDIES OF ADVERSE REPRODUCTIVE OUTCOMES IN
WORKERS EXPOSED TO ANTINEOPLASTIC DRUGS
OUTCOME
Population
Birth
Defect
Year
Author
1992
Skov
Onc Nurses
1993
Stucker
Onc Nurses
+ LBW, - SGA
1993
SaurelCubizolles
OR/Onc
Nurses
* Ectopic preg.
1995
Shortridge
Onc Nurses
1997
Valanis
Pharm +
RNs
1999
Valanis
Rn, Pharm
(M+F)
1999
Peelen
Onc
Nurses/Prep
+
Fetal
Loss
-
Other
+ Ectopic preg.
* Menstrual dysf.
* Infertility (F);
+ (M)
* (F);
+ (M)
-/*
-
+/* LBW
Key: (+) = effect seen, (-) = no effect seen, (*) = statistically significant effect seen, (F) = female; (M) = male; (LBW) = low birth wt;
(SGA) = small for gestational age.
Exposure Opportunity
• 1,250,000 new cancer patients in US
(ACS) in 2000; 500,000 will die
• 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
Exposure Opportunities in “Life Cycle” of Hazardous Drugs
Exposure Pathway in Life of
the Drug
A) Drug
Development/Manufacturing
Populations Affected
Manufacturing Personnel
R & D Personnel
212,000
199,500
2830
8731
B) Transport/Distribution
Transporters
Drug Distributors
184,597
197,702
4210
5722
C) Healthcare Facility
Pharmacy
Pharmacists
Pharmacy Techs
174,540
145,430
32517
32519
D) Drug Administration
Hospital-based
Registered Nurses
Outpatient Clinic-based
2,000,000
1,600,000
32502
8011
925,000
8082
1,255,210
66008
E) Home Care
Home Care
F) Waste Stream Issues
-Patient Waste
-Chemical contaminated
equipment,
tubing, packaging, etc.
Hospital/clinic/home
Nursing Aides/orderlies/
attendants
- Spill Responders
- Family
Numbers
SIC/OES
SOURCES OF CONTAMINATION
• Contaminated vials
• Drug preparation and administration
– Leaks
– Spills
• Drug relocation
• Spread of spills
• BSC/HVAC
ROUTES OF EXPOSURE
• Dermal
• Oral
• Inhalation
– Particulates (droplets, dusts)
– Vapors
SURFACE CONTAMINATION
• SESSINK ET AL, 1992a
METH
• SESSINK ET AL, 1992b
METH
• McDEVITT ET AL, 1993
• PETHRAN ET AL, 1998
• MINOIA ET AL, 1998
• CONNOR ET AL, 1999
• RUBINO ET AL, 1999
• SESSINK, ET AL, 1999
CP, 5-FU,
CP, 5-FU,
CP
CP, IF
CP, IF
CP, 5-FU, IF
5-FU, METH,CY,
GC
CP, 5-FUFU
AIR SAMPLING
(PARTICULATES)
• SESSINK ET AL, 1992a
• SESSINK ET AL, 1992b
METH/CP/IF
METH/CP/
5-FU
• McDEVITT ET AL, 1993 CP
• PETHRAN ET AL, 1998 CP
• MINOIA ET AL, 1998
CP/IF
VIAL CONTAMINATION
• SESSINK ET AL, 1992b
• HEPP & GENTSCHEW,
1998
AGENTS
• PETHRAN ET AL, 1998
• DELPORTE ET AL, 1999
CP, METH
SEVERAL
CP,IF
5-FU
URINE ANALYSIS







HIRST ET AL, 1984
VENITT ET AL, 1984
EVELO ET AL 1986
SESSINK ET AL, 1992a
1992b
ENSSLIN ET AL 1994a
1994b
SESSINK ET AL, 1994a
1994b
1994c
1994d
PETHRAN ET AL, 1998
CP
PT
CP
CP
CP, IF
PT
CP, IF +
FU
MTX
CP
CP
DOX
+
+
+
+
+
+
+
+
+
CONNOR ET AL, 1999
•
•
•
•
SIX CANCER CENTERS IN U.S. AND CANADA
PHARMACIES AND TREATMENT AREAS
CP, 5-FU, IF
BSCs, COUNTERS, CARTS, FLOORS, CHAIRS,
TABLES
• 75 % PHARMACY AND 65 % TREATMENT AREA
SAMPLES POSITIVE FOR AT LEAST ONE DRUG
• ADJACENT AREAS CONTAMINATED
VAPORIZATION OF
ANTINEOPLASTIC AGENTS
VAPOR PRESSURE*
DRUG
20ºC
25ºC
40ºC
5-FU
1.4
2.0
3.9
CP
3.3
4.4
9.0
IF
0.96
1.05
1.2
CIS
1.8
1.9
3.1
ETOP
2.6
2.65
3.8
BCNU
19
46
530
SCHMIDT ET AL, 1999
*mPa
CONNOR ET AL, 2000
VAPORIZATION OF AGENTS
DRUG
23ºC
37ºC
BCNU
CP
IF
THIO
MUST
+
+
+
+
+
+
+
+
Existing Handling Guidelines for
Hazardous Drugs
Source
Year
OSHA
1986, 1995
American Society of Health
System Pharmacists
1985, 1990
AMA Council on Scientific
Affairs
1985
Oncology Nursing Society
1988
Elements of Existing Guidelines
Include a Combination of
Controls:
• Substitution
•
•
•
•
•
Engineering
Work Practices/Administrative Controls
PPE
Training
Medical Surveillance
OSHA Hazardous Drug Document - 1995
•
•
•
•
•
•
•
Enlarges domain of drugs considered
ASHP definition of a hazardous drug
Includes agents in tablet form
Aerosolized agents
Hazard Communication Standard
Updated Appendix with source listed
Reproductive Hazards Policy
Evidence of Adherence to
Guidelines
• Not systematically studied
• Poor adherence is frequently cited in
individual studies in the literature
• Uncommonly cited by OSHA general duty
clause
• Not consistently surveyed by JCAHO
New Initiative
NIOSH Working Group
on
Safe Handling of Hazardous Drugs
• Federal Agencies (NIOSH, OSHA, NIH, FDA)
• Stakeholders
• Drug Manufactures
• Professional Organizations (ASHP, ONS)
• Home Care Providers
• Accreditation Bodies (JCAHO, ACHC, CHAP)
• Academia
Pharm Participants
Carmel Pharma
Abbott Laboratories
Bristol Myers Squibb
Amgen Inc.
Glaxo Smith Klein
Super Gen
Eli Lilly
Bochringer Ingilbeim
Merck & co.
Johnson & Johnson
Purpose:
Gather Public Health Agencies having jurisdiction and
affected stakeholders to
review current handling practices of hazardous drugs in
healthcare in light of new evidence suggesting current
practices are not adequately proactive;
recommend work practice changes and training needs
required to more adequately protect HCWs;
identify research needs;
and commit to work group.
Three Sub-groups
Engineering Controls
Work-Practices
Personal Protective Equipment
Consider a new type of
“Universal Precautions”
for handling these agents
• Performance-based
• Includes aspects of existing guidelines
and
• those to be added by working group
FUTURE
• NIOSH ALERT
• HARMONIZATION OF GUIDELINES
• ADDITIONAL RECOMMENDATIONS
www.OSHA.gov/outreach/technical links/
controlling occupational exposure to
hazardous drugs