Oncologic drug Exposure Risks and Prevention Guidelines 19 June 2014

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KITJAR RUANGTHAI M.D.

Oncologic drug Exposure Risks and

Prevention Guidelines

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KITJAR RUANGTHAI M.D.

สิ่งคุกคามซึ่งอาจเป็นอันตรายต่อสุขภาพ

HAZARD?

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KITJAR RUANGTHAI M.D.

Substitution

ENCLOSURE

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KITJAR RUANGTHAI M.D.

ADMINISTRATION

สิ่งคุกคามซึ่งอาจเป็นอันตรายต่อสุขภาพ

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KITJAR RUANGTHAI M.D.

Anticipation

(การคาดการณ์)

Recognition

(การตระหนัก)

Evaluation

(การประเมิน)

Control

(การควบคุม)

Indu

s

tria

l

H

ygie

ne

Man

ag

eme

nt

System

•Health Risk Assessment

Policy

Organization

Planning and Implementation

• Industrial Hygiene Survey • Hazard Inventory & Tracking

• Report

BEI

Prioritize Risk

IH Management

Exposure assessment

Prioritize Risk

Engineering control

Administration

- Training

- Risk Communication

- Chem Info System

Specific hazard, HCP

PPE, Respirator

Medical Surveillance

Evaluation

Action for Improvement

Toxicology review Health effects

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Hazard of Risk factors

Understand

material use

to determine

“

TOXICITY

”

Understand

situation of use

to estimate

“

EXPOSURE

”

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Source of Standard values



OSHA



NIOSH



ACGIH



IARC



MSDS



Chemical fact Sheets

:

Occupational Safety and Health Administration

:

National Institute for Occupational Safety & Health

:

A

merican

C

onference of

G

overnmental

I

ndustrial

H

ygienists

:

International Agency for Research on Cancer

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Abbreviations



TLV



TLV-C



TWA



PEL



REL



BEI



STEL



AL



IDLH

: Threshold Limit Value

: Threshold Limit Value-Ceiling

: Time-Weighted Average

: Permissible Exposure Level

: Recommended Exposure Level

: Biological Exposure Index

: Short Term Exposure Limit (15 min)

: Action Level

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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

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Antineoplastic Agents That are Classified as Known or Probable Human Carcinogens

IARC Group 1(Human Carcinogens) IARCGroup 2A (Probable Human Carcinogens)

Arsenic trioxide Azacitidine

Azathioprine BCNU Chlorambucil CCNU Chlornaphazine Chlorozotocin Cyclophosphamide Cisplatin Myleran Doxorubicin HCl Melphalan N-Ethyl-N-nitrosourea Semustine Etoposide Tamoxifen Mechlorethamine HCl Thiotepa N-Methyl-nitrosourea Treosulfan Procarbazine HCl Mustargen-Oncovin-Procarbazine-Prednisone Teniposide (MOPP) Etoposide-Cisplatin-Bleomycin (ECB)

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.

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Antineoplastic

**Agents That are Classified as Pregnancy Category D* or X†**

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Drug Pregnancy Category Drug Pregnancy Category

Arsenic trioxide D Imatinib mesylate D Azathioprene D Interferon alfa-2b X

Bleomycin D Irinotecan HCl D Capecitabine D Leflunomide X Carboplatin D Lomustine D Carmustine D Mechlorethamine HCl D Chlorambucil D Melphalan D Cisplatin D Mercaptopurine D Cladribine D Methotrexate X Cyclophosphamide D Mitoxantrone HCl D Cytarabine D Oxaliplatin D Dactinomycin D Paclitaxel D Daunorubicin HCl D Pipobroman D Docetaxel D Procarbazine D Doxorubicin HCl D Tamoxifin D Epirubicin D Temozolomide D Etoposide D Teniposide D Floxuridine D Thalidomide X Fludarabine D Thioguanine D Fluorouracil D Thiotepa D Gemcitabine D Topotecan D Hydroxyurea D Tositumomab X

Ibritumomab tiuxetan D Vinblastine sulfate D

Idarubicin D Vincristine sulfate D

Ifosfamide D Vinorelbine tartrate D

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Adapted from the US Food and Drug Administration Center for Drug Evaluation and Research.

D = Clear evidence of risk to the human fetus.

X = Clear evidence that medication causes abnormalities in the fetus.

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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

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17 Adapted from the National Institute for Occupational Safety and Health.

List of Hazardous Drug Handling Activities in Workers

Activity Primary Group of Workers Exposed

Handling drug - contaminated vials Pharmacists, pharmacy technicians

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

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 Pharmacists, pharmacy technicians, multi-dose bottles and nursing personnel

Unit-dosing uncoated tablets in a unit-dose machine

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List of Hazardous Drug Handling Activities in Workers

Activity

Primary Group of Workers Exposed Contacting measurable concentrations of drugs present on drug Pharmacists, pharmacy technicians,

vial exteriors, work surfaces, floors, and final drug products nursing personnel, (bottles, bags, cassettes, and syringes) housekeeping personnel

Handling unused antineoplastic drugs or antineoplastic drug contaminated waste

Decontaminating and cleaning drug preparation or clinical areas

Performing certain specialized procedures (such as intraoperative, Physicians, nursing personnel, and intra-peritoneal chemotherapy) in the operating room operating room personnel

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

Removing and disposing of personal protective equipment after Pharmacists, pharmacy technicians, handling hazardous drugs or waste nursing & housekeeping personnel

Performing repairs or maintenance on biological safety cabinets or Maintenance, biological safety isolators used to prepare antineoplastic drugs cabinets certification personnel

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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

,

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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)

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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

.

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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

)

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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.

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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

.

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• 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

drug-contaminated surfaces

- Routine operations

- Spill response

- Waste segregation, containment, and disposal

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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

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2. Handle drugs safely.

• 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

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2. Handle drugs safely.

• 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).

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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

,

needle-less systems

, and

PPE

.

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• 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

.

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• 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.

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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

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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

closed-system drug transfer devices)

as a substitution for ventilated

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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

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Types of Biological Safety Cabinets (BSC)

All types have

downward airflow

and

HEPA filters

BSC

The amount of

re-circulated air

within the

cabinet

Exhaust to

Contaminated duct pressure

room outside

negative

positive

Class II

Type A

70%

30%

-

_P

Type B1

30%

-

70%

_P

-

Type B2

-

100%

_P

-

Type B3

70%

-

30%

_P

-

Class III

- Totally enclosed with gas tight construction.

_{- 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.

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Air flow and exhaust

+

-

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Class I: BSC

Class II: BSC

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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 49

–

2002

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NIOSH Recommendations for Safe Handling of Antineoplastic and Other Hazardous Drugs

Activity Recommendations Routine cleaning, decontamination, - Use suitable PPE for the task being performed

housekeeping, and waste disposal - 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