11 Oncologic Drug Exposure Risks

Oncologic drug Exposure Risks and
Prevention Guidelines
19 June 2014
KITJAR RUANGTHAI M.D.
HAZARD?
HAZARD
ENCLOSURE
Substitution
ADMINISTRATION
Policy
Organization
Industrial Hygiene Management System
Planning and Implementation

Anticipation
()
Recognition
()
Evaluation
()
Toxicology review
Health effects
Control
()
Industrial Hygiene Survey

Hazard Inventory & Tracking
Prioritize Risk
IH Management
BEI Exposure assessment
Report
Health Risk Assessment
Prioritize Risk
Engineering control
Administration
- Training
- Risk Communication
- Chem Info System
PPE, Respirator
Specific hazard, HCP
Medical Surveillance
Evaluation
Action for Improvement
Hazard of Risk factors

Understand material use to determine
TOXICITY
Understand situation of use to estimate
EXPOSURE
HAZARD = TOXICITY X EXPOSURE
Source of Standard values

OSHA : Occupational Safety and Health Administration
NIOSH : National Institute for Occupational Safety & Health
ACGIH : American Conference of Governmental Industrial Hygienists

IARC : International Agency for Research on Cancer
MSDS : Material Safety Data Sheet

Chemical fact Sheets

9
Abbreviations
TLV
: Threshold Limit Value
TLV-C : Threshold Limit Value-Ceiling

TWA : Time-Weighted Average
PEL
: Permissible Exposure Level
REL
: Recommended Exposure Level
BEI
: Biological Exposure Index
STEL : Short Term Exposure Limit (15 min)

AL
: Action Level
IDLH : Immediately Dangerous to Life or Health

Characteristics That Define Hazardous Drugs

Carcinogenicity
Teratogenicity or other developmental toxicity
Reproductive toxicity
Organ toxicity at low doses
Genotoxicity
Structure & toxicity that mimics
existing hazardous drugs
Adapted from the National Institute for Occupational Safety and Health (NIOSH),
the Occupational Safety and Health Administration (OSHA), and
the American Society of Health-System Pharmacists
11
12
Antineoplastic Agents That are Classified as Known or Probable Human Carcinogens

IARC Group 1 (Human Carcinogens)
Arsenic trioxide
Azathioprine
Chlorambucil
Chlornaphazine
Cyclophosphamide
Myleran
Melphalan
Semustine
Tamoxifen
Thiotepa
Treosulfan
Mustargen-Oncovin-Procarbazine-Prednisone
(MOPP)
Etoposide-Cisplatin-Bleomycin (ECB)
IARC Group 2A (Probable Human Carcinogens)

Azacitidine
BCNU
CCNU
Chlorozotocin
Cisplatin
Doxorubicin HCl
N-Ethyl-N-nitrosourea
Etoposide
Mechlorethamine HCl
N-Methyl-nitrosourea
Procarbazine HCl
Teniposide
Adapted from the International Agency for Research on Cancer (IARC).
The majority of antineoplastic drugs are nonselective in their action: they exhibit their
effects in both cancerous and noncancerous cells in most organs and body tissues.
13
14
Antineoplastic Agents That are Classified as Pregnancy Category D* or X16

Drug Pregnancy Category
Arsenic trioxide
Azathioprene
Bleomycin
Capecitabine
Carboplatin
Carmustine
Chlorambucil
Cisplatin
Cladribine
Cyclophosphamide
Cytarabine
Dactinomycin
Daunorubicin HCl
Docetaxel
Doxorubicin HCl
Epirubicin
Etoposide
Floxuridine
Fludarabine
Fluorouracil
Gemcitabine
Hydroxyurea
Ibritumomab tiuxetan
Idarubicin
Ifosfamide
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
Drug Pregnancy Category

Imatinib mesylate
Interferon alfa-2b
Irinotecan HCl
Leflunomide
Lomustine
Mechlorethamine HCl
Melphalan
Mercaptopurine
Methotrexate
Mitoxantrone HCl
Oxaliplatin
Paclitaxel
Pipobroman
Procarbazine
Tamoxifin
Temozolomide
Teniposide
Thalidomide
Thioguanine
Thiotepa
Topotecan
Tositumomab
Vinblastine sulfate
Vincristine sulfate
Vinorelbine tartrate
D
X
D
X
D
D
D
D
X
D
D
D
D
D
D
D
D
X
D
D
D
X
D
D
D
D = Clear evidence
of risk to the
human fetus.
X = Clear evidence that
medication causes
abnormalities in
the fetus.
Adapted from the US Food and Drug Administration Center for Drug Evaluation and Research.
15
Potential for Worker exposure

Throughout its life cycle
These workers include
receiving personnel,
pharmacists and pharmacy technicians,
nursing personnel,
physicians,
operating room personnel,
environmental services personnel, and
housekeeping workers
16
List of Hazardous Drug Handling Activities in Workers

Activity
Handling drug - contaminated vials
Reconstituting powdered or lyophilized drugs and further diluting
either the reconstituted powder or concentrated liquid forms
of hazardous drugs
Expelling air from syringes filled with hazardous drugs
Compounding potent powders into custom-dosage capsules
Primary Group of Workers Exposed

Pharmacists, pharmacy technicians
Administering antineoplastic drugs by intramuscular, subcutaneous, Nursing personnel

or intravenous (IV) routes
Generating aerosols during the administration of drugs, either by
direct IV push or by IV infusion
Priming the IV set with a drug-containing solution at the patient
bedside
Handling body fluids or body-fluid-contaminated clothing,
dressings, linens, and other materials
Handling contaminated wastes generated at any step of the
preparation or administration process
Counting out individual, uncoated oral doses and tablets from
multi-dose bottles
Unit-dosing uncoated tablets in a unit-dose machine
Crushing tablets to make oral liquid doses
Pharmacists, pharmacy technicians,

and nursing personnel
KITJAR RUANGTHAI M.D. Adapted from the National Institute

for Occupational Safety and Health.
17
List of Hazardous Drug Handling Activities in Workers

Activity
Primary Group of Workers Exposed
Contacting measurable concentrations of drugs present on drug

vial exteriors, work surfaces, floors, and final drug products
(bottles, bags, cassettes, and syringes)
Handling unused antineoplastic drugs or antineoplastic drug
contaminated waste
Decontaminating and cleaning drug preparation or clinical areas

nursing personnel,
housekeeping personnel
Performing certain specialized procedures (such as intraoperative,

intra-peritoneal chemotherapy) in the operating room
Physicians, nursing personnel, and

operating room personnel
Transporting infectious, chemical, or hazardous waste containers
Nursing, housekeeping and

waste disposal personnel
Removing and disposing of personal protective equipment after

handling hazardous drugs or waste

nursing & housekeeping personnel
Performing repairs or maintenance on biological safety cabinets or

isolators used to prepare antineoplastic drugs
Maintenance, biological safety

cabinets certification personnel
Adapted from the National Institute for Occupational Safety and Health.
18
CONDITIONS FOR EXPOSURE

Both clinical and nonclinical workers may be
exposed to hazardous drugs when they create
aerosols,
generate dust,
clean up spills, or
touch contaminated surfaces
during the preparation, administration, or
disposal of hazardous drugs.
The following list of activities may result in
exposures through inhalation, skin contact,
ingestion, or injection:
19
Occupational exposures to hazardous drugs
can lead to Acute effects: headache, dizziness, nausea,
allergic reaction (asthma & skin rashes).

Chronic effects:
- increased genotoxic effects

- Developmental & reproductive events
- possibly cancer (leukemia)

20
Recent evidence summarized that

Worker exposure to hazardous drugs is a persistent problem.
The sampling methods used in the past have come into
question and may not be a good indicator of contamination
in the workplace.
Surface contamination of the workplace is common and
widespread.
A number of recent studies have documented the excretion
of several indicator drugs in the urine of healthcare workers.
Results from studies indicate that worker exposure to
hazardous drugs in health care facilities may result in adverse
health effects.
21
Hierarchy of Industrial Hygiene Control

Elimination of the hazard or substitution with a less
hazardous chemical (this is not feasible in health care)
Engineering controls (the use of biological safety cabinets,

isolators, or closed systems)
Administrative controls (training and education programs;
availability of material safety data sheets; established work
practices, policies, and surveillance)
Personal protective equipment (the use of protective gloves,
gowns, respiratory protection, and eye protection)
Adapted from Soule RD. Industrial Hygiene Engineering Controls
22
NIOSH recommends
NIOSH is currently conducting studies to further
identify potential sources of exposure and methods
to reduce or eliminate worker exposure to these drugs.
To minimize these potentially acute (short-term) and
chronic (long-term) effects of exposure to hazardous
drugs at work, that at a minimum, employers and
health care workers to follow.
23
Summary of NIOSH Recommended Procedures

1. Assessment the hazards in the workplace.
- Evaluate the workplace to identify & assess hazards.
- Regular review the current inventory of hazardous drugs,
equipment and practices, seeking input from affected workers.
- Conduct regular training reviews with all potential exposure
workers in workplaces where hazardous drugs are used.
2. Handle drugs safely.

- Implement a program for safely handling hazardous drug at
work and review this program annually.
- Establish procedures & provide training.
3. Use and maintain equipment properly.

24
1. Assess the hazards in the workplace.

Evaluate the workplace to identify and assess hazards.
- Total working environment
- Equipment (ventilated cabinets, closed-system drug transfer devices, glovebags, needleless systems & PPE)
- Physical layout of work areas
- Types of drugs being handled
- Volume, frequency & form of drugs handled (tablets, coated/uncoated, powder versus liquid)
- Equipment maintenance
- Decontamination and cleaning
- Waste handling
- Potential exposures during work, including hazardous drugs, bloodborne
pathogens, and chemicals used to deactivate hazardous drugs or clean drugcontaminated surfaces
- Routine operations
- Spill response
- Waste segregation, containment, and disposal
25
1. Assess the hazards in the workplace

Regularly review the current inventory of hazardous
drugs, equipment, and practices, seeking input from

affected workers.
Conduct regular training reviews with all potentially

exposed workers in workplaces where hazardous drugs
are used. Seek ongoing input from workers and use this
input from workers to provide the safest possible
equipment and conditions for minimizing exposures.
26

Implement a program for safely handling hazardous drugs
at work and review this program annually on the basis of
the workplace evaluation.
Establish work policies and procedures specific to the
handling of hazardous drugs. These policies and procedures
should address and define the following:
Presence of hazardous drugs
Labeling
Storage
Personnel issues (such as exposure of pregnant workers)
Spill control
Detailed procedures for preparing, administering &
disposing of hazardous drugs
27

Establish procedures and provide training for handling
hazardous drugs safely, cleaning up spills, and using all equipment
and PPE properly. Inform workers about the location and proper
use of spill kits. In addition, establish procedures for cleaning and

decontaminating work areas and for proper waste handling and
disposal of all contaminated materials, including patient waste.
Establish work practices related to both drug manipulation

techniques and to general hygiene practices - such as not
permitting eating or drinking in areas where drugs are handled

(the pharmacy or clinic).
28
3. Use and maintain equipment properly.

Develop workplace procedures for using and
maintaining all equipment that functions to
reduce exposure - such as ventilated cabinets,
closed-system drug-transfer devices, needleless systems, and PPE.
29
Wear PPE while reconstituting and admixing drugs:

- The gloves are labeled as chemotherapy gloves.
- Consider latex-sensitive workers and a number of glove
materials are suitable for protecting workers from
antineoplastic drugs.
- Consider using chemotherapy gloves for other hazardous
drugs or for which no information is available.
- Use double gloving for all activities involving hazardous
drugs. Make sure that the outer glove extends over the
cuff of the gown.
- Inspect gloves for physical defects before use.
- Prefer gloves with minimal or no powder.
Wear PPE while reconstituting and admixing drugs:

- Wash hands with soap and water before donning protective
gloves and immediately after removal.
- Change gloves every 30 minutes or when torn, punctured,
or contaminated. Discard them immediately in a yellow
chemotherapy waste container.
- Use disposable gowns made of polyethylene-coated
polypropylene. Make sure gowns have closed fronts,
long sleeves, and elastic or knit closed cuffs.
- Dispose of protective gowns after each use.
- Use disposable sleeve covers to protect the wrist area
and remove the covers after the task is complete.
31
NIOSH Recommendations for Safe Handling of Antineoplastic and Other Hazardous Drugs
Activity
Recommendations
Receiving and storage of drugs
- Wear PPE* suitable for task being performed

- Properly label all hazardous drugs
- Store and transport drugs in proper containers
Preparation and administration of drugs
- Evaluate drug preparation and administration policies

- Wear suitable PPE, including double gloves for task being performed
- Limit access to areas where drugs are prepared
- Use proper engineering controls when preparing drugs
- Wash hands with soap & water before donning and after removing gloves
- Prime intravenous tubing in a ventilated cabinet
- Use needleless or closed systems when preparing & administering drugs
- Do not disconnect tubing from an intravenous bag containing a
hazardous drug
- Dispose of used materials in the appropriate container
Ventilated cabinets
- Perform all preparations with hazardous drugs in a ventilated cabinet

designed to reduce worker exposure
- Do not use supplemental engineering controls as a substitute for a
ventilated cabinet
- When asepsis is required, select a cabinet designed for both hazardous
drugs containment and aseptic processing
- Horizontal laminar-flow clean benches should not be used for
preparation of hazardous drugs
- Properly maintain engineering controls as required by the manufacturer
32
Ventilated Cabinets
Use of cabinets
Mix, prepare, and otherwise manipulate, count, crush,
compound powders, or pour liquid hazardous drugs
inside a ventilated cabinet designed to prevent
hazardous drugs from being released into the work
environment.
Do not use supplemental engineering or process
controls (such as needleless systems, glove bags, and closedsystem drug transfer devices) as a substitution for ventilated
cabinets.
33
Selection a ventilated cabinet

Depending on the need for aseptic processing
- When asepsis is not required, a Class I BSC or an
isolator intended for containment applications
may be sufficient.
- When aseptic technique is required, use one of

the following ventilated cabinets:
a) Class II BSC (Type B2 is preferred)
b) Class III BSC
c) Isolators intended for asepsis and containment
34
Types of Biological Safety Cabinets (BSC)

All types have downward airflow and HEPA filters
The amount of
re-circulated air
within the
cabinet
room
outside
negative
positive
Type A
70%
30%
Type B1
30%
70%
Type B2
100%
Type B3
70%
30%
BSC
Class II
Exhaust to
Contaminated duct pressure
- Totally enclosed with gas tight construction.
Class III - The entire cabinet is under negative pressure

Class I
- Similar a chemical fume hood, but usually has a limited fixed work
access opening and the exhaust air must be HEPA filtered, to protect
the environment.
35
Air flow and exhaust
+
-
36
Class II: BSC
Class I: BSC
Class III: BSC
37
Air flow and exhaust

To confirm adequate air flow before each use.
Use a HEPA filter for the exhaust from these controls and
exhaust 100% of the filtered air to the outside.
Install the outside exhaust so that the exhausted air is not
pulled back into the building by HVAC systems or by the
windows, doors.
Place fans downstream of the HEPA filter so that contaminated
ducts are maintained under negative pressure.
Do not use a ventilated cabinet that recirculates air inside the
cabinet or exhausts air back into the room environment .
Seek additional information about placement of the cabinet,
exhaust system, and stack design from NSF/ANSI 492002
[NSF/ANSI 2002]. KITJAR RUANGTHAI M.D.
38
39
NIOSH Recommendations for Safe Handling of Antineoplastic and Other Hazardous Drugs
Activity
Recommendations
Routine cleaning, decontamination,

housekeeping, and waste disposal
- Use suitable PPE for the task being performed

- Establish periodic cleaning routines for all work surfaces and
equipment used where hazardous drugs are prepared or
administered
- Consider used linen and patient waste to be contaminated with the
drugs and/or their metabolites
- Separate wastes according to institutional, state, and federal
guidelines and regulations
Spill control
- Manage spills according to written policies and procedures

- Locate spill kits in areas where exposures may occur
- Adhere to Occupational Safety & Health Administration (OSHA)
respiratory protection program
- Dispose of spill material in a hazardous chemical container
Medical surveillance
- Participate in medical surveillance programs at work, or see your

private health care provider if one does not exist
- Medical surveillance should include the following:
Reproductive and general health questionnaires
Complete blood count and urinalysis
Physical examination at time of employment and annual health
status questionnaire review
Follow up for workers who have shown health changes
40
1. Assess the hazards in the workplace.
41
Housekeeping
Wear protective double gloves and a disposable gown if
you must handle linens, feces, or urine from patients who
have received hazardous drugs within the last 48 hours or
in some cases, within the last 7 days.
Dispose of the gown after each use or whenever it
becomes contaminated.
Wear face shields if splashing is possible.
Remove the outer gloves and the gown by turning them
inside out & placing them into the chemotherapy waste
container. Repeat the procedure for the inner gloves.
Wash hands with soap & water after removing the gloves.
42
Spill Control
Established written policies and procedures.
The size of the spill - authorized person to conduct the cleanup
& decontamination and how the cleanup is managed.
PPE required for various spill sizes, spreading of material,
restricted access to hazardous drug spills, and signs to be
posted.
Cleanup of a large spill is handled by workers who are trained.
Locate spill kits & other cleanup materials in the immediate
area where exposures may occur.
Surgical masks do not provide adequate protection.
Dispose of all spill cleanup materials in a hazardous chemical
waste container, not in a chemotherapy waste container.
43
The ASHP recommends that kits include:

chemical splash goggles,
two pairs of gloves,

utility gloves,
a low-permeability gown,
2 sheets (12" 12") of absorbent material,
250-ml and 1-liter spill control pillows,
a "sharps" container,
a small scoop to collect glass fragments, and
two large HD waste-disposal bags.
44
Q & Answer
45

46
http://www.ashp.org/doclibrary/bestpractices/prepgdlhazdrugs.aspx
47
https://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html
48
http://www.cdc.gov/niosh/docs/2004-165/
49

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Oncologic drug Exposure Risks and

KITJAR RUANGTHAI M.D.

KITJAR RUANGTHAI M.D.

KITJAR RUANGTHAI M.D.

Industrial Hygiene Management System

Planning and Implementation

Industrial Hygiene Survey

KITJAR RUANGTHAI M.D.

KITJAR RUANGTHAI M.D.

Hazard of Risk factors

Source of Standard values

ACGIH : American Conference of Governmental Industrial Hygienists

MSDS : Material Safety Data Sheet

KITJAR RUANGTHAI M.D.

: Threshold Limit Value

TLV-C : Threshold Limit Value-Ceiling

: Permissible Exposure Level

: Recommended Exposure Level

: Biological Exposure Index

STEL : Short Term Exposure Limit (15 min)

IDLH : Immediately Dangerous to Life or Health

Characteristics That Define Hazardous Drugs

KITJAR RUANGTHAI M.D.

Antineoplastic Agents That are Classified as Known or Probable Human Carcinogens

IARC Group 2A (Probable Human Carcinogens)

Adapted from the International Agency for Research on Cancer (IARC).

KITJAR RUANGTHAI M.D.

Antineoplastic Agents That are Classified as Pregnancy Category D* or X16

Drug Pregnancy Category

KITJAR RUANGTHAI M.D.

Potential for Worker exposure

List of Hazardous Drug Handling Activities in Workers

Primary Group of Workers Exposed

Administering antineoplastic drugs by intramuscular, subcutaneous, Nursing personnel

Pharmacists, pharmacy technicians,

KITJAR RUANGTHAI M.D. Adapted from the National Institute

List of Hazardous Drug Handling Activities in Workers

Primary Group of Workers Exposed

Contacting measurable concentrations of drugs present on drug

Pharmacists, pharmacy technicians,

Performing certain specialized procedures (such as intraoperative,

Physicians, nursing personnel, and

Transporting infectious, chemical, or hazardous waste containers

Nursing, housekeeping and

Removing and disposing of personal protective equipment after

Pharmacists, pharmacy technicians,

Performing repairs or maintenance on biological safety cabinets or

Maintenance, biological safety

KITJAR RUANGTHAI M.D.

CONDITIONS FOR EXPOSURE

Occupational exposures to hazardous drugs

can lead to Acute effects: headache, dizziness, nausea,

allergic reaction (asthma & skin rashes).

- increased genotoxic effects

- possibly cancer (leukemia)

Recent evidence summarized that

Hierarchy of Industrial Hygiene Control

Engineering controls (the use of biological safety cabinets,

Summary of NIOSH Recommended Procedures

2. Handle drugs safely.

3. Use and maintain equipment properly.

1. Assess the hazards in the workplace.

1. Assess the hazards in the workplace

drugs, equipment, and practices, seeking input from