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2/19/2018

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HAZARDOUS DRUG SAFETY and

USP <800>

Seth Eisenberg RN, OCN®, BMTCN®

Professional Practice Coordinator, Infusion Services

Seattle Cancer Care Alliance

Seattle, WA

PSONS March 2018

HAZARDOUS DRUG DEFINITION

• Defined by NIOSH as having any of the following characteristics:

• Carcinogenicity

• Teratogenicity or other developmental toxicity

• Reproductive toxicity

• Organ toxicity at low doses

• Genotoxicity

• Structure mimicking existing HD

NIOSH DRUG LIST EVOLUTION

2004 • Initial list came from 4 different (non-NIOSH) sources

• Beginning 2010, a new list is published every other year

• Allows 2 years to evaluate post-approval toxicities not seen in studies

• NIOSH uses expert review panel to scrutinize data

• Publishes draft in Federal Register for public comment

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NIOSH, 2016

Table Comments

1 Antineoplastic chemotherapy

2 Non-antineoplastics

3 Reproductive risk for personnel attempting to conceive or breast feeding

NIOSH DRUG TABLES

WHAT ABOUT TARGETED THERAPIES?

• Monoclonal antibodies have been generally

excluded from the NIOSH list, despite toxicities

satisfying the HD criteria

• Why?

• It’s all about size

WEIGHING IN: MABs

Bos & Meinardi, 2000

• Compounds > approximately 500 Daltons cannot be

absorbed via transdermal route

• FDA-approved transdermal (and topical)

medications are < 500 Daltons

Transdermal Drugs Molecular Mass (Daltons)

Scopolamine 305

Fentanyl 336

Nitroglycerine 227

Nicotine 162

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Drug Molecular Mass (Daltons)

5-Fluorouracil (5FU) 130

Cisplatin 300

Cyclophosphamide 279

Carmustine 214

Gemcitabine 263

Rituximab 143,860

Trastuzumab 145,532

Nivolumab 143,597

Obinutuzumab 146,100

Pembrolizumab 146,286

Daratumumab 148,000

WEIGHING IN: MABs

Tom Connor, NIOSH; www.drugbank.ca

WEIGHING IN: MABs

Comparing 143,800 Daltons (rituximab) to 500 Daltons… would be like comparing a 25 pound sack of flour to 1½ ounces of sugar

WEIGHING IN: MABs

Or for size, like trying to put a 10 foot pipe into an iPhone headphone jack

“If the molecule don’t fit, we must omit.”

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HAZARDOUS BUT NOT EQUAL

• Different handling precautions may be needed depending on the activity and formulation

• Example:

• “Unopened, intact tablets and capsules may not pose

the same degree of risk as IV medications. Cutting,

crushing, or otherwise manipulating tablets and

capsules will increase the exposure.”

NIOSH, 2016

RECENT WIPE TESTING STUDIES

SUMMARY OF RECENT STUDIES

Author Year n Findings

Hon, C-Y. et al

2013 438 36% of wipe tests in pharmacy and administration areas were positiveAreas included calculators, chairs, pens, printers keyboards and mouse

Hon, C-Y. et al

2014 110 20% of hand wipes (multidisciplinary staff) were positiveHighest level was on staff who were not administering HDs

Hon, C-Y. et al

2015 103 55% of urine samples were positive for CYHighest concentration in unit clerks and staff who were not administering HDs

Viegas, S. et al

2014 327 37% of wipe tests in pharmacy and administration areas were positiveAreas included infusion pumps, tables and door handles

Janes, A. et al

2015 584 50% of wipe tests in 51 Canadian hospitals were positive for CYContamination found in pharmacy and patient care areas including infusion chairs and on the counter

Poupeau, C. et al

2016 525 34% of wipe tests in 48 Canadian hospitals were positive for CYContamination found in pharmacy and patient care areas including infusion chairs and on the counter

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• Bartel, S. et al (2018):

• 13 NCI-designated cancer centers

• Wipe testing in pharmacy and infusion chairs (n =

156 samples).

• 55% of pharmacy samples were positive for CY

and/or 5FU.

• 78% of administration sites (chairs) were positive for

CY and/or 5FU.


Bartel, S., Tyler, T. & Power, L. (2018). Am J Health-Syst Pharm. 2018; 75:199-211

RECENT CHROMOSOMAL DAMAGE STUDIES


Author Year n Findings

McDiarmid, M. et al (3 us Cancer Centers)

2010 109 (46 control)

Abnormalities seen for chromosome 5 in exposed versus non-exposed (p=.01)

Increased incidence of chromosome 5 abnormalities with increased drug handling

Hazard Ratio 8.54 (p=.01) for alkylating agents

Moretti, C. et al.

2015 148 (77 control)

Signi cant increase in micronuclei (MN) frequency 5.30 ± 2.99 vs 3.29 ± 1.97; (p < 0.0001)

Chromosomal Aberrations detection3.30 ± 2.05 vs 1.84 ± 1.67; (p < 0.0001)

Ladeira, C. et al.

2014 138 (111 control)

Significant increase in MN frequency 2.08 ± .31 vs 10.11 ± 2.05; (p <.001)

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EXPOSURE ROUTE HIERARCHY

Handling Intact O

ral A

gents

Handling Feces

Spill M

anagement

Administration

Handling U

rine

Compounding

© 2017 S. Eisenberg

HOW EXPOSURE OCCURS

• Compounding using needles

• Incorrect BSC and or ventilation

• Contamination from exterior of vials

Courtesy of S. Eisenberg

HOW EXPOSURE OCCURS

• Spiking and unspiking at the bedside

• Connecting and disconnecting syringes and tubing

• Priming IV tubing

• Touching the exterior of the IV bag without wearing

proper PPE

• Wearing improper PPE

• Handling excreta

• Spills and leaks

Polovich, M., & Olsen, M. 2018, ONS.

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NIOSH HD SURVEY

• N = 1954 nurses

Survey Item %

Primed tubing with hazardous drug 6

Crushed tables or opened capsules (n=494) 13

Touched IV pump or bed controls while wearing chemotherapy gloves 61

Used pens or pencils while wearing chemotherapy gloves 26

Touched doorknobs or cabinets while wearing chemotherapy gloves 20

Never used a Closed System Transfer Device (CSTD) 47

Always wear double gloves 20

Always wear recommended gown 58

Reported a spill within prior week 12

Spills not always cleaned up 10

Boiano, Steege & Sweeney, 2014

HD GUIDELINES

US Pharmacopeial Convention

ASHP ASHP ONS OSHANIOSH Alert

1981 1983 1984 1986 2004

USP

2016*

ASHP ASHP ONS OSHAASHP ASHP ONS

UNITED STATES PHARMACOPEIA (USP)

• Most nurses have never

heard of USP but we’ve

seen their logo

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• The mission of USP is to set standards “for the

identity, strength, quality, and purity of

medicines…”

UNITED STATES PHARMACOPEIA (USP)

GUIDELINES VS. STANDARDS

Guidelines

• Recommended practice

• Evidence-based

• What “should” be

• Example:

• ONS Chemotherapy

Guidelines

Standards

• Expectations for practice

• Evidence-based

• What “must” be

• Example:

• The Joint Commission

• CMS

USP CHAPTER 800 (USP <800>)

• Includes standards for:

• HD delivery and storage

• Education

• Compounding

• Administration

• Disposal

*

**

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USP <800>

• Is enforceable by:

• Each state’s Board of Pharmacy

• Designated agency (e.g., Department Of

Health)

• The FDA

• CMS (through USP <797>)

o CMS currently has COPs with USP for USP <797>

*CMS Standard §482.25(a) (https://www.cms.gov/Regulations-and-Guidance/Legislation/CFCsAndCoPs/Hospitals.html)

USP <800>

Compliance date: December 1, 2019

USP <800> REQUIREMENTS

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USP <800> REQUIRED EDUCATION

• A designated individual must be in charge of the HD

program

• All employees must have access to and understand the

organization’s HD list

• Education must be provided for all staff handling HDs

before performing any HD-related duties

• Assessment of competency must be performed

annually and documented

• All staff of reproductive capability must sign an

acknowledgement of HD risks

• Worn during:

• Compounding

• Administration

• Disposal

• Spill Cleanup

• (Handling excreta)

PERSONAL PROTECTIVE EQUIPMENT


• Double-gloves for handling HDs

• BOTH pair must be chemotherapy tested to

ASTM D6978-05 standards

• Do not need to be the same brand of glove for the

inner and out pair

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• Not all chemotherapy gloves are created equal:

DrugMinimum breakthrough

time (minutes)

Cardinal Cool Blue Cardinal Esteem

Carmustine (BCNU) 7.28 17.14

Cisplatin >240 >240

Cyclophosphamide >240 >240

Doxorubicin >240 >240

Etoposide >240 >240

5FU >240 >240

Methotrexate >24 Not Tested

Paclitaxel >40 >240

Thiotepa 2.67 1.16

• Chemotherapy-resistant gown

• “Single-use” and disposable

• Solid front and elastic or knit cuffs

• Shown to resist HD permeability

• There are no current standards for gowns

• Ask the manufacturer to provide proof of HD

resistance

Polovich, M., & Olsen, M. 2018, ONS.; Eisenberg, S. 2017


SPILL MANAGEMENT

• Spill training with appropriate respiratory protection

for drugs that vaporize at room temperature

• Carmustine

• Etoposide

• Cyclophosphamide

• Thiotepa

• Nitrogen Mustard

• 5-FU

• Cisplatin

• Ifosfamide

Connor, Shults & Fraser, 2000; Kiffmeyer et al, 2002

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VAPORS AND AEROSOLS

• Vapors: small particles (e.g., perfume)

• Aerosols: larger particles (e.g., Windex™)

• N95 or N100 are for aerosols and particulates

• Vapors require a canister respirator or PAPR

(Powered Air Purifying Respirator) with organic

vapor cartridge

DHHS (NIOSH) Publication No. 2009–106; USP<800> 2016

Full Face Respirator with OV canister

PAPR (Powered Air Purifying Respirator) with OV cartridge

VAPORS AND AEROSOLS

Photos: S. Eisenberg

CLOSED SYSTEM TRANSFER DEVICE

• A Closed System Transfer Device (CSTD) will be required for administration of antineoplastic HDs

• Designed to “restrict hazardous drug liquid or vapor from escaping into the environment.”

• CSTDs are recommended for compounding

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7 CSTD SYSTEMS AVAILABLE

• Halo (Corvida)

• Phaseal (BD)

• Equashield (Equashield Medical)

• OnGuard (B Braun)

• ChemoLock (ICU Medical)

• ChemoClave (ICU Medical)

• Chemo Safety System [Texium] (CareFusion/BD)

• For administering drugs in a syringe (IVP, SC, IM)

• On all IV chemotherapy bags if attaching at

bedside or disconnecting bag from tubing

• Used at the end tubing (secondary tubing and/or

primary)

CSTDs

Eisenberg, S. 2018

GENERAL CSTD COMPARISON

Manufacturer Device Luer / Membrane

Notes

BD Phaseal Membrane First to market (1999)

BD ChemoSafety [Texium] Luer Designed to work with CareFusion Smartsite™ valve

B Braun OnGuard Membrane Dual layer microfilters on vial adapter

Corvida Halo Membrane New; limited availability

Equashield Equashield II Membrane Dual-chamber syringes

ICU Medical ChemoClave Luer Universal luer compatibility

ICU Medical ChemoLock Membrane Needless

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CSTD OPTIONS

• Direct Spikes: Allows for direct connection to HD bag using CSTD on tubing

• Dry Spikes: Allows for spiking of tubing at the bedside without risk of puncturing the IV bag

CSTD EFFECTIVENESS

• Still no standardized test for effectiveness

• NIOSH is working on a second draft protocol for testing

• Products that passed 1st protocol:

• ChemoLock

• Phaseal

• Equashield

• OnGuard

PREPARING FOR USP <800>

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DETERMINE WHO’S IN CHARGE

• All aspects of HD safety must be overseen by an

individual responsible for

• development of any additional HD policies and

procedures

• monitoring for compliance with USP <800> and state

and Federal regulations

• Should work with members of an interdisciplinary

team

IDENTIFY AREAS OF VULNERABILITY

• Perform a gap analysis between USP <800> and current policies and practice

• Several free tools available

• HazMedSafety.com (Joint Commission Resources)

• 800gaptool.com (Critical Point)

• Compounding Today.com “USP <800> Gap

Analysis Tool.5”

Eisenberg, S. 2016; Walton, A. 2012


• Must have SOPs covering:

Gloves meeting the ASTM 6978 standard

Hazard communication and occupational safety

programs

Designation of HD areas

Receipt and storage of HDs

Compounding and dispensing of HDs

Use and maintenance of proper engineering

controls (e.g., C-PECs, C-SECs, and CSTDs)

Eisenberg, S. 2018

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• Must have SOPs covering:

Hand hygiene and use of PPE based on activity

(e.g., receipt, transport, compounding,

administration, spill, and disposal)

Deactivation, decontamination, cleaning, and

disinfection

HD Transport

HD Administration

HD disposal and spill control

Eisenberg, S. 2018


• Determine if:

Gloves meet the ASTM 6978 standard

Gowns meet the USP <800> requirements

Disposal meets USP <800> requirements


• Education meets the requirements:

Occurs prior to HD handling

Documented

Performed annually



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• Spill Management

Staff trained to manage a spill

Staff are available whenever HDs are administered

Staff have the requisite respiratory protection for

drugs that vaporize

Staff treat every spill as if it was MRSA or Ebola



CSTD are in place for antineoplastic HD

administration

Documentation that staff have been trained

Verify that staff are using the device



IDENTIFY BARRIERS FOR SAFETY COMPLIANCE

• Poor staffing (workload)

• Lack of education about HD dangers

• PPE not meeting staff needs (e.g., gowns or

gloves that do not fit)

• Workplace culture does not support HD safety

Callahan 2016; Polovich & Clark 2012

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CHANGE WORKPLACE CULTURE

• Find Hazardous Drug champions!

• Staff nurses

• Advanced Practice Nurses

• Clinical educators

• Department manager

• Pharmacy manager

• Department medical director

• Risk manager

Eisenberg, S. 2016

CHANGE WORKPLACE CULTURE

Eisenberg, S. 2016

• Adopt a zero-tolerance approach to preventing

exposure within the workplace

• Increase nursing awareness of the risks associated with

hazardous drugs through multiple mediums and

methods

• Staff meetings

• Local chapter presentations

• Newsletters

ADDITIONAL RESOURCES

• www.ready4800.com

• www.usp.org/frequently-asked-

questions/hazardous-drugs-handling-

healthcare-settings

• https://www.cdc.gov/niosh/docs/2016-

161/default.html

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