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The BD PhaSeal™ systemClinical evidence compendiumA summary of the clinical evidence of the effectiveness of the BD PhaSeal™ Closed-System Drug Transfer Device (CSTD).

2

Dear Reader,

Every day, hundreds of thousands of healthcare workers prepare and administer hazardous drugs to treat patients with life-threatening conditions. While these drugs have a demonstrated patient benefit, they can also pose a significant risk to healthcare professionals.

This evidence summary was compiled in order to facilitate the reader’s ease of accessing the literature pertinent to the BD PhaSeal System. All studies in this compendium were found via a literature search and are provided as a courtesy to you, the reader. All information in this summary was current as of December 1, 2016 and BD is not liable for any inaccuracies therein.

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Table 1............................................................................... 4-11Studies examining the impact of hazardous drugs on environmental contamination and personnel exposure

Table 2............................................................................ 12-14Studies evaluating microbial integrity and pharmacy economics

Table 3................................................................................... 15Studies evaluating the impact of CSTD implementation and efficiency

References (1–33)..............................................................16

Table of contents

4

Date of publication 2016 2014 2013

First author Simon1 Pasternak (poster)2 Miyake3

Study name

Effectiveness of a closed-system transfer device in reducing surface contamination in a new antineoplastic drug compounding unit: A prospective, controlled, parallel study

Evaluation of syringe plunger contamination during hazardous drug preparation

Impact of closed-system drug transfer device on exposure of environment and healthcare provider to cyclophosphamide in Japanese hospital

Method

Investigate the ability of a closed-system transfer device (CSTD; BD PhaSeal) to reduce the occupational exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding devices.

The study protocol was limited to 12 BD syringes. Twelve BD 60ml syringes were divided into three equal groups. Using PhaSeal, 50 mL aliquots of cyclophosphamide were removed and re-injected back into the vial. Using ChemoGlo sampling kits, the exposed plunger rods were wiped for cyclophosphamide contamination and sent for quantitative evaluation using liquid chromatograph tandem mass spectroscopy.

This study was conducted to compare surface contamination and personnel exposure to cyclophosphamide before and after the implementation of a CSTD, PhaSeal, under the influence of cleaning according to the Japanese guidelines.

Results – environmental exposure

At the end of the study, a total of 686 surface samples were measured. Overall contamination was lower in the “PhaSeal” isolator than in the “Standard” isolator (12.24% vs 26.39%; p<0.0001) although it differed according to drug.

The highest level of cyclophosphamide detected on a syringe was 207.98 ng/ft2 which was lower thant what was detected in the Smith/Szalaczk study.

Four of 6 wipe samples collected before PhaSeal indicated a detectable level of cyclophosphamide. About 7 months after the initiation of PhaSeal, only one of 6 wipe samples indicated a detectable level of cyclophosphamide.

Results – personnel exposure

Not applicable in this study. Not applicable in this study.

Although all 4 employees who provided urine samples had positive results for the urinary excretion of cyclophosphamide before PhaSeal, these levels returned to minimal levels in 2 pharmacists after PhaSeal.

Conclusions

This study confirms that using a CSTD may significantly decrease the chemical contamination of barrier isolators compared to standard devices for some drugs, although it does not eliminate contamination totally.

These data suggests that there is no contamination of the syringe plungers, or at worst, it is no higher than 150 ng/ft2, which is more than 10 times less than previously studied by Smith and Szalaczk.

PhaSeal further reduces surface contamination and healthcare providers exposure to cyclophosphamide to almost undetectable levels.

Journal name PLoS ONE ASHP Conference SpringerPlus

Peer-reviewed Yes Yes Yes

RESEARCH Open Access

Impact of closed-system drug transfer device onexposure of environment and healthcare providerto cyclophosphamide in Japanese hospitalTomohiro Miyake1,2, Takuya Iwamoto2,3, Manabu Tanimura1 and Masahiro Okuda2,3*

Abstract

In spite of current recommended safe handling procedures, the potential for the exposure of healthcare providersto hazardous drugs exists in the workplace. A reliance on biological safety cabinets to provide total protectionagainst the exposure to hazardous drugs is insufficient. Preventing workplace contamination is the best strategy tominimize cytotoxic drug exposure in healthcare providers. This study was conducted to compare surfacecontamination and personnel exposure to cyclophosphamide before and after the implementation of a closed-system drug transfer device, PhaSeal, under the influence of cleaning according to the Japanese guidelines.Personnel exposure was evaluated by collecting 24 h urine samples from 4 pharmacists. Surface contamination wasassessed by the wiping test. Four of 6 wipe samples collected before PhaSeal indicated a detectable level ofcyclophosphamide. About 7 months after the initiation of PhaSeal, only one of 6 wipe samples indicated adetectable level of cyclophosphamide. Although all 4 employees who provided urine samples had positive resultsfor the urinary excretion of cyclophosphamide before PhaSeal, these levels returned to minimal levels in 2pharmacists after PhaSeal. In combination with the biological safety cabinet and cleaning according to theJapanese guidelines, PhaSeal further reduces surface contamination and healthcare providers exposure tocyclophosphamide to almost undetectable levels.

Keywords: Cyclophosphamide, Surface contamination, exposure of healthcare provider, PhaSeal, Japaneseguidelines

BackgroundMany drugs used in the treatment of cancer are consid-ered to be hazardous to healthcare workers. Over the last20 years, several studies have reported environmental con-tamination with hazardous drugs in hospital pharmacies(Castiglia et al. 2008; Ensslin et al. 1994; Hedmer et al.2008; McDevitt et al. 1993; Sessink et al. 1992; Sessinket al. 1995; Sugiura et al. 2011; Vandenbroucke and Robays2001; Yoshida et al. 2011). In addition, hazardous drugswere inadvertently absorbed, as determined by the pres-ence of parent compounds and/or their metabolites inthe urine of health care workers (Ensslin et al. 1997;Schreiber et al. 2003; Sessink et al. 1992; Sessink et al.

1994; Sessink et al. 1997). Due to the potential healthrisks of hazardous drugs, the increasing use of thesedrugs, and continuing environmental contamination, theNational Institute for Occupational Safety and Health(NIOSH) published an alert for antineoplastic and otherhazardous drugs used in healthcare settings (NationalInstitute for Occupational Safety and Health NIOSH2004). Based upon recommendations, the AmericanSociety of Health-System Pharmacists (ASHP) and theInternational Society of Oncology Pharmacy Practi-tioners (ISOPP) have published updated guidelines onthe safe-handling of cytotoxic and hazardous drugs(American Society of Health-System Pharmacists guide-lines on handling hazardous drugs 2006; InternationalSociety of Oncology Pharmacy Practitioners StandardsCommittee. ISOPP standards of practice 2007).In Japan, guidelines for handling antineoplastic drugs

in hospitals were issued by the Japan Pharmaceutical

* Correspondence: [email protected] of Clinical Pharmacy and Biopharmaceutics, Mie UniversityGraduate School of Medicine, Mie, Japan3Department of Pharmacy, Mie University Hospital, Mie, JapanFull list of author information is available at the end of the article

a SpringerOpen Journal

© 2013 Miyake et al.; licensee Springer. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproductionin any medium, provided the original work is properly cited.

Miyake et al. SpringerPlus 2013, 2:273http://www.springerplus.com/content/2/1/273

RESEARCH ARTICLE

Effectiveness of a Closed-System TransferDevice in Reducing Surface Contamination ina New Antineoplastic Drug-CompoundingUnit: A Prospective, Controlled, Parallel StudyNicolas Simon1,2☯*, Michèle Vasseur1,2☯, Marine Pinturaud2, Marion Soichot3,Camille Richeval4, Luc Humbert4, Michèle Lebecque2, Ousseini Sidikou2,Christine Barthelemy1, Pascal Bonnabry5, Delphine Allorge4, Bertrand Décaudin1,2,Pascal Odou1,2

1 EA 7365 –GRITA—Groupe de Recherche sur les formes Injectables et les Technologies Associées,F-59000, Lille, France, 2 CHU Lille, Institut de Pharmacie, F-59000, Lille, France, 3 Laboratoire deToxicologie, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France, 4 UnitéFonctionnelle de Toxicologie, Pôle de Biologie-Pathologie-Génétique, CHRU Lille, F-59037, Lille, France,5 Pharmacy, Geneva University Hospitals and School of Pharmaceutical Sciences, University of Geneva,University of Lausanne, Geneva, Switzerland

☯ These authors contributed equally to this work.* [email protected]

Abstract

Background

The objective of this randomized, prospective and controlled study was to investigate the

ability of a closed-system transfer device (CSTD; BD-Phaseal) to reduce the occupational

exposure of two isolators to 10 cytotoxic drugs and compare to standard compounding

devices.

Methods and Findings

The 6-month study started with the opening of a new compounding unit. Two isolators were

set up with 2 workstations each, one to compound with standard devices (needles and

spikes) and the other using the Phaseal system. Drugs were alternatively compounded in

each isolator. Sampling involved wiping three surfaces (gloves, window, worktop), before

and after a cleaning process. Exposure to ten antineoplastic drugs (cyclophosphamide,

ifosfamide, dacarbazine, 5-FU, methotrexate, gemcitabine, cytarabine, irinotecan, doxoru-

bicine and ganciclovir) was assessed on wipes by LC-MS/MS analysis. Contamination

rates were compared using a Chi2 test and drug amounts by a Mann-Whitney test. Signifi-

cance was defined for p<0.05. Overall contamination was lower in the “Phaseal” isolator

than in the “Standard” isolator (12.24% vs. 26.39%; p < 0.0001) although it differed accord-

ing to drug. Indeed, the contamination rates of gemcitabine were 49.3 and 43.4% (NS) for

the Standard and Phaseal isolators, respectively, whereas for ganciclovir, they were 54.2

and 2.8% (p<0.0001). Gemcitabine amounts were 220.6 and 283.6 ng for the Standard and

Phaseal isolators (NS), and ganciclovir amounts were 179.9 and 2.4 ng (p<0.0001).

PLOS ONE | DOI:10.1371/journal.pone.0159052 July 8, 2016 1 / 17

a11111

OPEN ACCESS

Citation: Simon N, Vasseur M, Pinturaud M, SoichotM, Richeval C, Humbert L, et al. (2016) Effectivenessof a Closed-System Transfer Device in ReducingSurface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled,Parallel Study. PLoS ONE 11(7): e0159052.doi:10.1371/journal.pone.0159052

Editor: Aamir Ahmad, University of South AlabamaMitchell Cancer Institute, UNITED STATES

Received: December 18, 2015

Accepted: June 27, 2016

Published: July 8, 2016

Copyright: © 2016 Simon et al. This is an openaccess article distributed under the terms of theCreative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in anymedium, provided the original author and source arecredited.

Data Availability Statement: All relevant data arewithin the paper and its Supporting Information files.

Funding: The study was funded by Becton-Dickinson laboratories, manufacturer of the testeddevice. The funder had no role in study design, datacollection and analysis, decision to publish, orpreparation of the manuscript.

Competing Interests: The study was funded byBecton-Dickinson laboratories, manufacturer of thetested device. There are no patents, products in

Table 1 Studies examining the impact of hazardous drugs on environmental contamination and personnel exposure

THE OHIO STATE UNIVERSITY COMPREHENSIVE CANCER CENTER - ARTHUR G. JAMES CANCER HOSPITAL AND RICHARD J. SOLOVE RESEARCH INSTITUTE

Evaluation of syringe plunger contamination during hazardous drug preparation

Kiersten M. Pasternak, PharmD Candidate 20161, Ryan M. Connell CPhT1, Ryan Forrey, PharmD, MS, FASHP1, Fouzia Berdi, PharmD2, Richard Gonzalez, PharmD, MBA2

1The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute; 2Nebraska Methodist Hospital

Purpose

The purpose of this study was to replicate the experiment published in the Journal of Oncology Pharmacy Practice “Syringe plunger contamination by hazardous drugs: a comparative study” by Stephen T Smith and Mark C Szalaczk. This study reported high levels of hazardous drug contamination on the syringe plunger when using Becton Dickinson® (B-D) 60 mL syringes to perform a series of withdrawal and injection cycles. However, other published syringe plunger contamination studies do not show similar levels of contamination. If accurate, this data may influence safe handling measures taken intended to reduce exposure for those who work with hazardous drugs.

Methods Discussion

Conclusions

Results

Disclosures This study was funded by a grant from Becton-Dickinson. Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation: Kiersten Pasternak: Nothing to Disclose Ryan Connell: Nothing to Disclose Ryan Forrey: Consultant for B-D Fouzia Berdi: Nothing to Disclose Richard Gonzalez: Nothing to Disclose

The protocol was developed after a detailed review of the original article. The study protocol was limited to B-D syringes, so syringes from Equashield® were excluded in our study. • Four 2 gram cyclophosphamide vials were

reconstituted using 100 mL of 0.9% sodium chloride.

• Twelve B-D 60 mL syringes were divided into three equal groups. Using Phaseal®, 50 mL aliquots of cyclophosphamide were removed and re-injected back into the vial. • The first group of syringes underwent two

withdraw and return cycles each • The second group of syringes underwent four

withdraw and return cycles each • The third group underwent eight withdraw and

return cycles each

• After the last cycle, the syringes were retracted to

the 50 mL position and disengaged from the vial. • Using ChemoGlo™ sampling kits, the exposed

plunger ribs were wiped for cyclophosphamide contamination and sent for quantitative evaluation using liquid chromatograph tandem mass spectrometry (LC-MS/MS).

Location Description Cyclophosphamide Concentration ng/ft2(ng/cm2)

Control: BSC work surface before experiment

ND

Control: BSC work surface before experiment

ND

Vials 1-4 ND Syringe 1A – 1D: 2 withdrawal and return cycles

ND

Syringe 2A-2D: 4 withdrawal and return cycles

ND

Syringes 3A-3D: 8 withdrawal and return cycles

ND

Negative Control ND Control: BSC work surface after experiment

ND

Control: BSC work surface after experiment

ND

Positive Control >4000 (>4.31)

• All manipulations were performed by technicians extensively trained in chemotherapy preparation.

• The technician’s chemotherapy gloves were changed after reconstitution, between each group, and after each wipe test.

• Techniques demonstrated in this experiment are not true to actual practice. • These techniques would result in a higher

likelihood of contamination compared to real-life practice of single-use syringes.

• Even with the erroneous samples due to the flooded LC-MS/MS system, the highest level of cyclophosphamide detected on a syringe was 207.98 ng/ft2, which was lower than what was detected in the Smith/Szalaczk study (Mean amount of contamination: >1621.91 ng.)

• Due to the quantitative system failure, the LLQ was raised to 150 ng/ft2, but all samples were ND at this level.

• These data suggests that there is no contamination of the syringe plungers, or at worst, it is no higher than 150 ng/ft2, which is more than 10 times less than previously published by Smith and Szalaczk.

• A more real-life experimental design should be used for future tests of syringe plunger contamination.

• Quantities less than the lower limit of quantification (LLQ) are defined as non-detectable (ND).

• The LLQ for this study was 150 ng/ft2 (0.16 ng/cm2). • The LLQ was raised in our experiment from 10

ng/ft2 to 150 ng/ft2. • A positive control sample tested before our

samples flooded ChemoGlo’ s LC-MS/MS instrumentation and contaminated all subsequent samples.

• The change in the LLQ is based on the change in the LC-MS/MS system and assay induced by the high positive control sample.

Image from B-D Plunger Wipe Test Protocol

Image from B-D Plunger Wipe Test Protocol

5


First author De Ausen4 Sessink5 Favier6

Study name Leakage from closed-system transfer devices as detected by a radioactive tracer

Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device

The PhaSeal system: Impact of its use on workplace contamination and duration of chemotherapy preparation

Method

Three CSTDs (the ChemoClave, OnGuard and PhaSeal systems) were tested by 9 oncology pharmacists and pharmacy technicians to determine the degree of leakage of a liquid test agent (a radioactive technetium isotope diluted in normal saline).

Surface contamination with the antineoplastic drug cyclophoshamide was compared in 30 US hospital pharmacies from 2004 to 2010 following preparation with standard drug preparation techniques or the PhaSeal closed system transfer device.

Five skilled pharmacy technicians prepared a total of 100 chemotherapy preparations using the standard procedure and 100 using the PhaSeal system. Fluorescein was used, which becomes fluorescent when exposed to UV light. We timed the duration of the different steps of the manipulation.


ANOVA results indicated significant differences among devices in leakage of the test solution, with the PhaSeal device having the lowest geometric mean leakage followed by the OnGuard and ChemoClave devices.

With the use of CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination with cyclophosphamide was observed (P<.0001). Median values for surace contamination with cyclophosphamide were reduced by 86% comapred to 95% in the previous study.

A major reduction in the contamination of the work environment when using the PhaSeal system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used. On the duration of the preparation, our results indicate that this duration would be approximately 1 hour longer for the preparation of 100 samples.


Not applicable in this study. Not applicable in this study. Not applicable in this study.

Conclusions

This study provides scientific support for the recommendations put forth by NIOSH and ASHP that CSTDs should be used to prepare antineoplastic medications.

The CSTD significantly reduced, but did not totally eliminate, surface contamination with cyclophosphamide. In addition to other measures, increased usage of CSTDs should be employed to help protect health care workers from exposure to hazardous drugs.

The study clearly established the benefit of using BD PhaSeal for protecting the staff members who work with hazardous agents. It also indicated that the duration of drug preparation is not impacted by the use of the BD PhaSeal system.

Journal name American Journal of Health System Pharmacists

Hospital Pharmacy Journal of Oncology Pharmacy Practice


Hosp Pharm 2013;48(3):204–2122013 � Thomas Land Publishers, Inc.www.thomasland.comdoi: 10.1310/hpj4803-204

Original Article

Reduction in Surface Contamination With Cyclophosphamidein 30 US Hospital Pharmacies Following Implementation of

a Closed-System Drug Transfer Device

Paul J.M. Sessink, PhDp; Jason Trahan, PharmD†; and Joseph W. Coyne, RPh‡

AbstractPurpose: In a follow-up to a previous study, surface contamination with the antineoplastic drugcyclophosphamide was compared in 30 US hospital pharmacies from 2004 to 2010 followingpreparation with standard drug preparation techniques or the PhaSeal closed system drugtransfer device (CSTD).Methods: Wipe samples were taken from biological safety cabinet (BSC) surfaces, BSC airfoils (thefront leading edge of the BSC), floors in front of BSCs, and countertops in the pharmacy, and theywere analyzed for contamination with cyclophosphamide. Contamination was reassessed aftera minimum of 6 months following the implementation of the CSTD. Surface contamination (ng/cm2)was compared between the 2 techniques and between the previous and current test periods andevaluated with the Kruskal-Wallis test.Results: With the use of CSTD compared to the standard preparation techniques, a significantreduction in levels of contamination with cyclophosphamide was observed (P , .0001). Medianvalues for surface contamination with cyclophosphamide were reduced by 86% compared to 95%in the previous study.Conclusions: The CSTD significantly reduced, but did not totally eliminate, surface contam-ination with cyclophosphamide. In addition to other protective measures, increased usage ofCSTDs should be employed to help protect health care workers from exposure to hazardousdrugs.

Key Words—antineoplastic agents, closed system drug transfer device, cyclophosphamide, drugpreparation, hospital pharmacies, surface contamination

Hosp Pharm—2013;48(3):204–212

Antineoplastic and other hazardous drugs maycause adverse health effects in health careworkers who handle them.1-21 Therefore, efforts

to reduce or eliminate exposure to these drugs are es-sential to the health care community. To achieve this,class II biological safety cabinets (BSCs) and personalprotection were introduced several decades ago.22,23

Despite these measures, environmental contaminationwith antineoplastic drugs in hospital pharmacies is stillobserved and health care workers are still exposed.24-29

In 2004, the National Institute for OccupationalSafety and Health (NIOSH) published an Alert on

hazardous drugs used in health care settings.30 Basedon the Alert, the American Society of Health-SystemPharmacists (ASHP) published updated guidelineson the safe handling of hazardous drugs in 2006,31 andsafe handling of hazardous drugs is included in UnitedStates Pharmacopeia (USP) Chapter ,797..32

In the NIOSH Alert, the ASHP guidelines, and inUSP,797., recommendations were presented to reduceenvironmental contamination and exposure of healthcareworkers to these drugs.One recommendationwas toconsider the use of closed system drug transfer devices(CSTDs) in addition to engineering controls. Since the

*Chemist and President, Exposure Control Sweden AB, Bohus-Bjorko, Sweden; †Manager of Clinical Pharmacy Services, BaylorAll Saints Medical Center, Fort Worth, Texas; ‡Vice President of Pharmacy Services, Cancer Treatment Centers of America,Schaumburg, Illinois. Corresponding author: Dr. Paul J.M. Sessink, Exposure Control Sweden AB, Backsippevagen 2, SE - 475 37Bohus-Bjorko, Sweden; phone: (46) 702 692260; e-mail: [email protected]

204 Volume 48, March 2013

OncologyPharmacyPractice

Journal of

Article

The PhaSeal� system: Impact of its use onworkplace contamination and duration ofchemotherapy preparation

B FavierDepartment of Pharmacy, Centre Leon Berard, Lyon, France

H LabrosseDepartment of Pharmacy, Centre Leon Berard, Lyon, France

L Gilles-AfchainDepartment of Pharmacy, Centre Leon Berard, Lyon, France

C CropetCentre Leon Berard, Unite de biostatistique et d’evaluation des therapeutiques, Lyon, France

D PerolCentre Leon Berard, Unite de biostatistique et d’evaluation des therapeutiques, Lyon, France

N ChaumardDepartment of Pharmacy, Centre Leon Berard, Lyon, France

JF LatourDepartment of Pharmacy, Centre Leon Berard, Lyon, France

P HildDepartment of Pharmacy, Centre Hospitalier de Roanne, Roanne, France

Abstract

Purpose. The primary objective of this study was to compare the levels of environmental contamination before and

after the introduction of PhaSeal� (closed-system drug transfer device) in two hospital pharmacies. Our secondary

objective was to assess the impact of the device on the duration of drug preparation compared to procedures involving

the use of needles and syringes.

Methods. The study involved two French hospitals, which prepared antineoplastic chemotherapy using a biological

safety cabinet and an isolator. Five skilled pharmacy technicians at each hospital prepared a total of 100 chemotherapy

preparations using the standard procedure and 100 using the PhaSeal� system. To control for possible contamination

occurring in the course of the procedure, we used fluorescein which becomes fluorescent when exposed to UV light. To

reply the second objective, we timed the duration of the different steps of the manipulation.

Results. Our findings showed a major reduction in the contamination of the work environment when using the PhaSeal�

system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used.

On the duration of preparation, our results indicate that this duration would be approximately 1 h longer for the

preparation of 100 samples.

Conclusion. In conclusion, this study clearly establishes the benefit of using PhaSeal� for protecting the staff members

who work with hazardous agents. It also indicates that the duration of drug preparation is not impacted by the use of the

system.

Corresponding author:

Bertrand Favier, Departement de Pharmacie, Centre Leon Berard, 28 rue

Laennec, 69008 Lyon, France

Email: [email protected]

J Oncol Pharm Practice

0(0) 1–9

! The Author(s) 2011

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DOI: 10.1177/1078155211401454

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Practice rePorts closed-system transfer devices

619Am J Health-Syst Pharm—Vol 70 Apr 1, 2013

Leakage from closed-system transfer devices as detected by a radioactive tracer

Lorena De ausen, erik F. DeFreitas, Latisha LittLeton, anD MichaeL Lustik

Purpose. A study of leakage from selected closed-system transfer devices (CSTDs) un-der experimental conditions is described.Methods. Three CSTDs (the ChemoClave, OnGuard, and PhaSeal systems) were tested. Nine manufacturer-trained oncol-ogy pharmacists and pharmacy techni-cians volunteered to participate in an experiment to determine the degree of leakage of a liquid test agent (a radioac-tive technetium isotope [99mTc] diluted in normal saline) during CSTD-assisted transfer of liquid from vials to syringes per standard practices. After such trans-fers, alcohol prep pads (n = 135 for each system) were used to wipe CSTD points of entry and assessed for the presence of 99mTc. Comparisons among participants and devices were conducted via analysis of variance (ANOVA), with the a priori level of significance set at 0.05.

Lorena De Ausen, Pharm.D., is Clinical Pharmacist, Depart-ment of Pharmacy, Tripler Army Medical Center, Honolulu, HI; at the time of writing she was Pharmacy Resident, Department of Pharmacy, Tripler Army Medical Center. MAJ Erik F. DeFreitas, Pharm.D., BCOP, is Chief of Oncology Practice, Department of Pharmacy, Tripler Army Medical Center. MAJ Latisha Littleton, Pharm.D., is Chief of Pharmacy, 168th Multifunctional Medical Battalion, Camp Walker, Daegu, South Korea; at the time of writ-ing she was Chief of Nuclear Pharmacy, Department of Pharmacy, Tripler Army Medical Center. Michael Lustik, M.S., is Statisti-cian, Department of Clinical Investigation, Tripler Army Medical Center.

Address correspondence to MAJ Erik F. DeFreitas, 1 Jarrett White Road, Honolulu, HI 96859 ([email protected]).

Lou Shimabuku, CHP, and 1LT Matthew Tullia are acknowledged

for serving as advisors on the proper handling and disposal of the technetium used in this research.

Funded by the Department of Pharmacy, Tripler Army Medical Center. All devices were purchased using funds from the Department of Pharmacy. Proprietary information or results of ongoing research may be subject to different interpretations. Investigators agree to abide by the noncommercialism guidelines.

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Depart-ment of the Army, Department of Defense, or the U.S. government.

Presented in part at the Western States Conference, Monterey, CA, May 26, 2011, and at the University of Hawaii, Hilo, September 20, 2011.

The authors have declared no potential conflicts of interest.

DOI 10.2146/ajhp110678

Results. ANOVA results indicated signifi-cant differences among devices in leakage of the test solution, with the PhaSeal device having the lowest geometric mean leak-age (0.1 nL; 95% confidence interval [CI], 0–0.2 nL), followed by the OnGuard (1.5 nL; 95% CI, 1.1–1.9 nL) and ChemoClave (35.6 nL; 95% CI, 29.1–43.6 nL) devices; each pairwise comparison was significant (p < 0.001). Despite several major limitations, the research supports the use of CSTDs to help protect health care workers, as recommended by federal authorities and professional groups including the Ameri-can Society of Health-System Pharmacists.Conclusion. The volume of leakage was significantly less with PhaSeal than with OnGuard and ChemoClave when pharma-cists and pharmacy technicians used the three CSTDs and 99mTc as a tracer.Am J Health-Syst Pharm. 2013; 70:619-23

Hazardous drugs are termed by the National Institute for Oc-cupational Safety and Health

(NIOSH) as agents that exhibit a potential for carcinogenicity, terato-genicity, reproductive toxicity, organ toxicity at low doses, or genotoxic-ity.1,2 The number of workers who may be exposed to hazardous drugs exceeds 5.5 million, with the risk extending to each step in drug devel-opment, distribution, preparation, administration, and disposal.2 There are consequences of unintentional contamination of antineoplastics in the workplace that have been re-ported through case reports.1-4 While some hazardous drug-associated adverse events are acute and easily correlated with exposure, chronic effects tend to progress more slowly and their etiology is more difficult to ascertain.

NIOSH and the American Soci-ety of Health-System Pharmacists (ASHP) are proponents for the use of closed-system transfer de-vices (CSTDs) in combination with

a biological safety cabinet having vertical air flow, personal protective equipment, and proper handling practices.1,2 While the definition of a closed system is somewhat debatable,

NIOSH defines a CSTD as a “drug transfer device that mechanically prohibits the transfer of environ-mental contaminants into the system and the escape of hazardous drug


6


First author Sessink7 Nishigaki8 Siderov9

Study name

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device

The usefulness of a closed system device for the mixing of injections to prevent occupational exposure to anticancer drugs

Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device

Method

Surface contamination was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal CSTD.

A comparative investigation of chemical contamination between the traditional preparation (using needles and syringes) and preparation using closed system devices.

This was a pre- and post-intervention study in which the chemical contamination was tested at baseline then at 5 and 12 months after the introduction of a closed system transfer device.


Using the CSTD compared to the standard preparation techniques, a significant reduction in levels of contamination was observed in all drugs.

There was no contamination observed in any parts of any observed cases for preparation using PhaSeal, regardless of preparation experience. There was no scattering of chemicals on the surface of equipment and BSC for tests using FL, and the results showed very low amounts of CPA detected.

After 5 months, the total contamination was reduced by 24%. After 12 months, total contamination of surfaces tested was reduced by 68%.



Conclusions

Use of BD PhaSeal significantly reduces surface contamination when preparing cyclophosphamide, ifosfamide, and 5-fluorouracil as compared to standard drug reparation techniques.

Results of this investigation showed that preparation using needles and syringes had a significantly higher frequency of contamination. Closed system devices can significantly prevent the contamination of BSC surfaces.

When used inside a CDSC, the closed system drug transfer device BD PhaSeal further reduces surface contamination in some instances to undetectable levels.

Journal name Journal of Oncology Pharmacy PracticeJournal of Japanese Society of Hospital Pharmacists

Journal of Oncology Pharmacy Practice



Reduction in surface contamination withantineoplastic drugs in 22 hospital pharmaciesin the US following implementation of aclosed-system drug transfer device

Paul JM Sessink, PhD1

Thomas H Connor, PhD2

James A Jorgenson, RPh MS FASHP3

Timothy G Tyler, PharmD FCSHP4

Purpose. Surface contamination with the antineo-plastic drugs cyclophosphamide, ifosfamide, and5-fluorouracil was compared in 22 US hospitalpharmacies following preparation with standarddrug preparation techniques or the PhaSeal�

closed-system drug transfer device (CSTD).Methods. Wipe samples were taken from biolog-

ical safety cabinet (BSC) surfaces, BSC airfoils, floorsin front of BSCs, and counters and analyzed forcontamination with cyclophosphamide, ifosfamide,and 5-fluorouracil. Contamination was reassessedseveral months after the implementation of theCSTD. Surface contamination (ng/cm2) was com-pared between the two techniques and evaluatedwith the Signed Rank Test.Results. Using the CSTD compared to the stan-

dard preparation techniques, a significant reduction

in levels of contamination was observed for alldrugs (cyclophosphamide: p50.0001; ifosfamide:p50.001; 5-fluorouracil: p50.01). Median valuesfor surface contamination with cyclophosphamide,ifosfamide, and 5-fluorouracil were reduced by 95%,90%, and 65%, respectively.Conclusions. Use of the CSTD significantly

reduces surface contamination when preparingcyclophosphamide, ifosfamide, and 5-fluorouracilas compared to standard drug preparationtechniques. J Oncol Pharm Practice (2010) 0:1–10.

Key words: antineoplastic agents; closed-systemdrug transfer device; surface contamination;drug preparation; hospital pharmacies;cyclophosphamide

INTRODUCTION

Over the last 20 years, several studies have beenpublished showing environmental contaminationwith antineoplastic drugs in hospital pharmacies.1–28

In addition, several studies have shown that anti-neoplastic drugs are inadvertently absorbed byhealthcare workers through environmental exposureas determined by the presence of the parentcompound and/or its metabolite(s) in theirurine.12,18,29–41

1Exposure Control B.V., Wijchen, The Netherlands; 2Division ofApplied Research and Technology, National Institute forOccupational Safety and Health (NIOSH), Cincinnati, OH, USA;3Clarian Health Partners Inc., Methodist Hospital, Indianapolis, IN,USA; 4Desert Regional Medical Center/Comprehensive CancerCenter (Aptium Oncology, Inc.), Palm Springs, CA, USA

Corresponding author: Dr. Paul J.M. Sessink, ExposureControl B.V., P.O. Box 467, NL-6600AL Wijchen, TheNetherlands. Tel: (31) 24 6452745; Fax: (31) 24 6452746.E-mail: [email protected]

J Oncol Pharm Practice (2010) 0: 1–10

� The Author(s), 2010. Reprints and permissions:http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/1078155210361431

J Oncol Pharm Pract OnlineFirst, published on February 15, 2010 as doi:10.1177/1078155210361431

7


First author Yoshida10 Jorgenson11 Nyman12

Study name

Use of a closed system device to reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment

Contamination comparison of transfer devices intended for handling hazardous drugs

Workplace contamination with antineoplastic agents in a new cancer hospital using a closed-system drug transfer device

Method

Compared the contamination by and exposure to cyclophosphamide between a conventional mixing method and a mixing method using a closed system device.

Titanium tetrachloride was selected to simulate the escape of vapor from each product. Fluorescent sodium was selected to simulate contamination with the dry connections between the vial and syringe and between the syringe and access port.

After 6 months of operation, surface samples were collected from pharmacy and nursing areas to determine levels of contamination with cyclophoshamide and ifosfamide. In addition, urine samples were collected from pharmacists, pharmacy technicians, and nurses to determine employee exposure to these agents. All samples were analyzed using liquid chromatography/tandem mass spectrometry.


Using the closed system device significantly reduced the surface contamination of CPA for all wipe sampling points in the preparation room. Using the closed system device significantly reduced the gloves contamination of CPA.

In the first test, only the PhaSeal system prevented the release of titanium and, therefore, met the NIOSH and ISOPP definition of closed.

Results of the second test validated that only the PhaSeal system contained the drug throughout all preparation and administration manipulations.

Twenty-one% (7/34) of surface samples collected tested positive for cyclophosphomide contamination. Twelve% (4/34) of surface samples tested positive for ifosfamide.


Following BD PhaSeal: cyclophosphamide contamination in the urine of pharmacists was significantly reduced compared to conventional mixing method.

Not applicable in this study.The urine of one participant (1/11), a pharmacy technician, tested positive for low levels of cyclophosphamide and ifosfamide.

Conclusions

A closed system transfer device can reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment.

Only the PhaSeal system met the NIOSH and ISOPP definitions of a CSTD.

Compared with historical levels of contamination in our outpatient oncology infusion clinic, levels of chemotherapy contamination appeared lower. However, some contamination was still present in our new cancer hospital where PhaSeal had been used exclusively.

Journal name Annals of Occupational Hygiene Hospital Pharmacy Hospital Pharmacy



8


First author Harrison13 Tans14 Wick15

Study name

Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed system drug transfer device versus standard preparation techniques

Comparative contamination study with cyclophosphamide, fluorouracil and ifosfamide: standard technique versus a proprietary closed handling system

Using a closed system protective device to reduce personnel exposure to antineoplastic agents

Method

Wipe samples of the various surfaces in each pharmacy were obtained biweekly for 12 weeks (six samples) to establish a baseline. Following implementation of the CSTD, an additional six biweekly samples were collected. The CSTD was then removed, and a final six samples were collected again using standard preparation techniques. During the CSTD phase, fluorourcil was prepared on the counter top outside the BSC.

The objective of this study was to compare the surface and glove contamination with CPA, ifosfamide and fluorouracil following preparation using either a standard admixture technique or the fully enclosed PhaSeal system.

During a period of 4 months CPA and fluorouracil were prepared with the PhaSeal system. Following a period of 2 months using the classical technique, CPA and ifosfamide were prepared for an 18 month period with the PhaSeal system. Samples were taken before the start of the 4 month period in the middle and at the end of the PhaSeal period, 2 months after stopping PhaSeal and again after 18 months of working with PhaSeal. The total number of samples was 104.

Surface contamination and personnel exposure to antineoplastic agents before and after the implementation of a closed-system protective device were studied. Both types of samples were analyzed for cyclophosphamide and isofamide by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Samples were collected before and six months after implementation of PhaSeal. Personnel exposure was evaluated by collecting 24-hour urine samples.

Results – Environmental Exposure

During the 36-week study, 342 samples were collected. A total of 8% positive fluorouracil wipe samples were found in the three pharmacies. The proportion of positive fluorouracil samples was significantly less in the CSTD phase than in the control phases. There were 324 positive cyclophosphamide wipe samples. The median surface contamination was significantly different across the three phases. This was consistent at all sites, for both the BSC work surfaces and counter tops. Contamination on floors adjacent to the BSCs was not consistently reduced.

The use of the PhaSeal system does not show a clear difference in the measured amount of contamination on surfaces. However, the rather large spill due to an incorrect use of the system could have influenced the results. The contamination of the gloves on the other hand shows an explicit improvement with the use of the PhaSeal system.

All 17 wipe samples collected before implementation of PhaSeal had detectable levels of CPA and 11 were positive for ifosfamide. Six months after system implementation, 7 of 21 wipe samples had detectable levels of CPA and 15 were positive for ifosfamide.

Results – Personnel Exposure

Not applicable in this study. Not applicable in this study.

Of eight employees who provided urine samples, six were positive for CPA and two for ifosfamide before implementation, and none were positive for either drug after implementation.

Conclusions

The use of a CSTD in the BSC in conjunction with standard HD preparation techniques significantly reduced cyclophosphomide surface contamination as compared to standard techniques alone. Preparation of fluorouracil outside the BSC using the CSTD did not result in significant analytically detectable contamination on the countertops.

Good compliance with standard preparation and cleaning techniques results in equal levels of contamination on surfaces compared with the PhaSeal system. However, the PhaSeal system is an important improvement in reducing contamination on gloves.

The PhaSeal system appeared to reduce surface contamination with and exposure of health care personnel to cyclophosphamide and ifosfamide.

Journal name American Journal of Health System Pharmacy Journal of Oncology Pharmacy Practice American Journal of Hospital Pharmacists



9


First author Spivey16 Connor17 Nygren18

Study name

Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV preparation with a closed system

Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area

Exposure to anti-cancer drugs during preparation and administration. Investigations of an open and a closed system

Method

Fluorescein was prepared as a dry powder and a .05% solution in empty drug vials. Each phase of the manipulation was photographed using UV light to visualize leaks and spills. The procedures included reconstitution of a dry powder, drug transfer from the vial to an IV bag, simulated drug administration, and IV push administrations through an IV port.

When the renovation of the pharmacy was completed and the new BSCs were installed, wipe samples were collected from 18 locations in the pharmacy area before drug preparation commenced. Thereafter, all doses of both cyclophosphamide and ifosfamide were routinely prepared using the PhaSeal system. As a control, all doses of fluorouracil were prepared using the standard method. After the baseline sampling, the 18 locations were sampled every four weeks for each of the three agents. Sampling continued for a period of 24 weeks, resulting in six post-intervention sampling dates.

Platinum, determined using adsorptive voltammetry, was used as the tracer for airborne emission. For determination of spills and leakage onto surfaces the radioisotope 99m-technetium was used as the tracer.


With the conventional needle/syringe technique, each phase of the manipulations resulted in visible fluorescein leakage into the environment. With PhaSeal no leakage was observed during any phase of the manipulations.

The results of the present study show that contamination inside a BSC is contained through the use of a closed-system device. However, because of the extreme sensitivity of the detection technique and the apparent ineffectiveness of the routine cleaning procedures, the issue becomes more complex than might have been suspected.

The mean airborne emission was 6ng m-3 with the closed system and 15 ng m-3 with the traditional pump technique. The average surface spillage using the closed technique was 0.0005µL. This is significantly smaller that with the traditional technique, which resulted in an average spillage of 64 µL.



Conclusions

A closed system such as BD PhaSeal has the ability to confine hazardous drugs, substantially reducing or possibly eliminating drug exposures.

A closed-system device, in conjunction with the use of BSCs, in an i.v. admixture area, appeared to contain surface contamination resulting from the preparation of cyclophosphamide and ifosfamide.

Using the closed system the leakage is 3-4 orders of magnitude lower in comparison with the open system. Even inexperienced nurses can, after a short introduction, use this technique without spills above 0.1 µL.

Journal name Hospital PharmacyAmerican Journal of Health Systems Pharmacists

Journal of Environmental Monitoring



10

Date of publication 2001 1999

First author Vandenbroucke19 Sessink20

Study name How to protect environment and employees against cytotoxic agents: The UZ Ghent experience

Evaluation of the PhaSeal hazardous drug containment system

Method

Compare two different systems for the reconstitution and preparation of cytotoxic drug-containing infusion bags. The Classical system (open) uses Luer lock syringes and needles, and the PhaSeal system (closed) uses special devices. Both wipe samples of the Biological Safety Cabinet (BSC) plus surroundings and urine analysis of technicians and pharmacists involved in the preparatory activities were used. Analyses were performed using gas chromatography in tandem with mass spectroscopy.

The PhaSeal system was tested in an outpatient setting in Sweden for 1 year during the preparation and administration of cyclophosphamide, fluorouracil and similar cytostatic drugs. The study was designed to determine the effectiveness of PhaSeal in preventing the leakage of cytostatic drugs. Cytostatic drugs were prepared and administered using standard safety procedures, except that a biological safety cabinet was not used.


The results of the wipe sampling indicate that:

Contamination occurs rapidly

Contamination once present is hard to remove

When working with the classical system, a minimal 10-fold increase in contamination of the surrounding area occurs

When working with the PhaSeal system, there is a decrease of contamination in the surrounding area

Vertical class II BSCs do not have the protection capacity previously assumed, especially if an open system and the external exhaust fails

The cleaning procedures should be further examined to establish new, more effective potent procedures.

At the end of the study period, environmental contamination was determined from wiping samples of objects and surfaces in the drug preparation room. Neither cyclophosphamide nor fluorouracil was found in any of these samples.


The results of the urine tests indicate that:

Working with the PhaSeal system leads to only one positive urine test of an assistant preparing cytotoxic drugs

Working with the classical system leads to four positive urine tests of assistants preparing cytotoxic drugs, one positive test of a pharmacist present in the same room and one negative sample.

Not applicable in this study.

Conclusions

By using closed systems, both personnel and their surroundings are protected and therefore, as a result of the contamination study, the pharmacy staff together with the general direction of the hospital decided that for preparatory activities of cytotoxic drugs, the PhaSeal system should be used.

Results show that use of the PhaSeal system alone is sufficient to prevent environmental contamination during the preparation of cytostatic drugs.

Journal name Journal of Oncology Pharmacy Practice Hospital Pharmacy

Peer-reviewed Yes Yes


Hospital Pharmacy 1311

PEER-REVIEWED ARTICLE

Evaluation of the PhaSeal Hazardous Drug Containment System

Paul J. M. Sessink, PhD,* Mary-Ann E. Rolf, RN,** and N. Stefan Rydèn, MD, PhD†

Hospital PharmacyVolume 34, Number 11, pp 1311–1317

1999 Facts and Comparisons

PEER-REVIEWED ARTICLE

Cytostatic drugs are widelyused in the treatment ofcancer and certain non-neoplastic diseases.1–3

This class of drugs exhibits a highdegree of biological activity andacts primarily by interfering with thesynthesis of DNA during the replica-

tion of tumor cells, resulting in amarked decrease in the replicationof malignant cells.

Cytostatic drugs are highly non-selective in their activity, however,resulting in extensive damage tonormal (nontumor) cells during nor-mal replication. Health care workersare routinely exposed to low levelsof these drugs in the workplace,potentially on a daily basis.

TOXIC SIDE EFFECTSPatients treated with cytostatic

drugs commonly exhibit acute anddose-limiting side effects, includingirritation of the skin, eyes, andmucuous membranes; alopecia;nausea; vomiting; and diarrhea.More toxic side effects have beendocumented in bone marrow, liver,bladder, kidney, and lung tissue.1,2,4,5

The long-term toxic side effectsof cytostatic drugs include muta-genic, carcinogenic, and reproduc-tive changes.3 The InternationalAgency for Research on Cancer(IARC) has determined that a suffi-cient body of data exists to support

Abstract — PhaSeal is a containment system designed to ensure thesafe preparation and administration of cytostatic drugs and thus reduceenvironmental contamination to work areas and to medical and supportstaff. The PhaSeal system was tested in an outpatient setting in Swe-den for 1 year during the preparation and administration of cyclophos-phamide, fluorouracil, and similar cytostatic drugs. The study wasdesigned to determine the effectiveness of PhaSeal in preventing theleakage of cytostatic drugs frequently reported in a number of studies.Cytostatic drugs were prepared and administered using standard safe-ty procedures, except that a biological safety cabinet was not used. Atthe conclusion of the study period, environmental contamination wasdetermined from wiping samples of objects and surfaces in the drugpreparation room. Neither cyclophosphamide nor fluorouracil was foundin any of these samples. Results show that use of the PhaSeal systemalone is sufficient to prevent environmental contamination during thepreparation of cytostatic drugs.

Key Words — cytostatic drugs; environmental contamination;cyclophosphamide; fluorouracil; closed system; containment device

Hosp Pharm — 1999;34:1311–1317

*Chemist/Toxicologist, Exposure Control, Wijchen, The Netherlands; **Oncology Nurse Specialist, Oncology Outpatient Clinic, ÄngelholmHospital, Ängelholm, Sweden; †Associate Professor, Department of Surgery, Ängelholm Hospital, Ängelholm, Sweden

Address correspondence to Paul J. M. Sessink, Exposure Control, P.O. Box 467, 6600 AL Wijchen, The Netherlands. Tel: (31) 24 645 2745; Fax: (31) 24 645 27 46; E-mail: [email protected]

Portions of this study were presented by Dr. Sessink at the M.D. Anderson Cancer Center’s 19th Annual Pharmacy Symposium on Can-cer Chemotherapy, October 5–7, 1997, in Houston, TX.

Financial support for this study was provided by Carmel Pharma ab, P.O. Box 5352, S-40228 Göteborg, Sweden. Tel (46) 31 703 04 00;Fax (46) 31 703 04 04. PhaSeal is manufactured and marketed by Carmel Pharma ab, P.O. Box 5352, SE-40228, Göteborg, Sweden. Tel:(46) 31 703 0400; Fax: (46) 31 703 0404. In the United States, PhaSeal is marketed by Carmel Pharma Inc., One Reservoir Corporate Cen-ter, Suite 206, Research Drive, Shelton, CT 06484. Tel: 203-925-8821; Fax: 203-925-8890; E-mail: [email protected]

11


First author Ho21 Sánchez-Rubio Ferrández22 Edwards23

Study nameDetermination of extended sterility for single-use vials using the PhaSeal closed-system transfer device

CSTDs and microbiological stability of cytostatics

Cost savings realized by use of BD PhaSeal closed-system transfer device for preparation of antineoplastic agents

Method

Prospective, observational study, fluorouracil aliquots were transferred to tryptic soy broth culture medium in intravenous bags over a 2-week period. Twelve aliquots and 96 bags were used. The bags and their contents were stored at 35° C for 14 days, and were monitored for evidence of microbial contamination.

The cytostatic drug elaboration process was simulated using Tryptone soy broth culture medium. The process was repeated on different days (0,1,4,7) with the same vials. Two different storage conditions were tested. Ten batches of eight vials were prepared by 5 different operators. Resulting syringes, bags and vials were incubated for 14 days at 25-35°.

A list of 25 drugs available in single-use vials, with a chemical stability of at least 48 hours was compiled. Use of these agents was recorded during a 50-day period in April through June 2012. Use from a total of 296 vials of 21 antineoplastic agents was recorded. After allowing for the initial use of each vial, the mean potential percentage of drug waste was calculated to be 57.03%.

ResultsNo microbial growth was observed throughout the 14-day period. Thus, at 336 hours (14 days), the probability of failure was 0%.

All 740 product samples (320 IV bags, 320 syringes) were negative for microbial growth regardless of the operator, the number of manipulations or the temperature of storage. After seven days, all 80 vials remained sterile at end of study even those with at least nine punctures of the BD PhaSeal membranes.

Actual savings during the study period was $96,348.70. The pharmacy avoided nearly half of the potential waste and saved a mean of 29% of each vial. The cost-saving during the study period represents a $703,047.67 annual saving; which more than offsets the $106,556.55 the pharmacy spent for the PhaSeal system.

Conclusions/implications

The PhaSeal system maintains the sterility of unpreserved injectable solutions and can apparently be used to extend the BUD of single-use vials for >= 7 days. Findings support those of previous studies of PhaSeal’s utility in the reduction of medication waste, and the realization of significant cost-savings for parenteral medications.

Study showed that using the BD PhaSeal system maintained the sterility of the final product for at least seven days.

In addition to being a protective measure to reduce expose to hazardous agents, use of the PhaSeal system results in a reduction in drug waste, and a noticeable cost savings for antineoplastic agents.

Journal name Journal of Hematology Oncology Pharmacy Hospital Pharmacy Europe Journal of Oncology Pharmacy Practice


Table 2 Studies evaluating microbial integrity and pharmacy economics

43

www.hospitalpharmacyeurope.com

Pharmacy practiceIssue 69 | July/August 2013

This study evaluated the microbiological stability of cytostatics manipulated using the BD PhaSeal® system inside a biological safety cabinet, and results demonstrate PhaSeal's clear benefits in maintaining product sterility in real practice

CSTDs and microbiological stability of cytostatics

Javier Sánchez-Rubio Ferrández PharmD PhDPharmacy Department, Hospital Universitario de Getafe, Madrid, SpainBlanca Rodríguez Vargas PharmDPharmacy Department, Jimenez Díaz Foundation, Madrid, Spain Luis Sánchez-Rubio Ferrández PharmDMaría del Carmen Lozano Estevan PharmD PhDPharmaceutical Technology, Alfonso X University, Villanueva de la Cañada, Madrid, SpainIrene Iglesias Peinado PharmD PhDVidedean Faculty of Pharmacy, Complutense University, Madrid, SpainEmail: [email protected]

Cancer is a major public healthproblem worldwide that has an elevated social impact due to morbidity and mortality, and which causes a serious financial burden to society.

Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occurred in 2008 worldwide.1 Consequently, cytostatic drug compounding has become a major challenge for hospital pharmacy services.

The pharmacist is responsible for compounding sterile products of the correct ingredients, purity, strength, and sterility, and accurate labelling and dispensing in appropriate containers for the end user. The expiry date should be based on available chemical stability data and sterility considerations.2

Regarding microbiological stability, pharmaceutical manufacturers usually quote very short stability data, reflecting a care principle that considers the possibility of bacterial contamination and

the fact that most of the drugs do not contain preservatives. In many cases, immediate use is instructed in the product information so that extended use is now a user responsibility, and this depends on the capability of implementing a proper aseptic technique.

Cytostatic compounding is a technical challenge because it is necessary to implement correct aseptic technique to maintain product sterility while minimising potential occupational and environmental exposure owing to the deleterious effects of this class of drugs.3

Health professionals who work in chemotherapy preparation and administration are exposed to these compounds in different ways (for example, dermal contact, inhalation, ingestion) and several observational studies have demonstrated that working surfaces and different objects (such as gloves and vials) are contaminated with antineoplastic agents regardless of the use of biological safety cabinets. Urine analysis of exposed workers in other studies has also revealed that systemic absorption of these compounds is a possibility.4–6 The exposure could lead to harmful effects such as genotoxicity, reproductive toxicity, and carcinogenicity.7–9

The traditional technique of a needle and syringe to extract drugs from vials has been shown to lead to greater

contamination levels due to aerosols, spills, leakages or losses across the rubber stopper of the vial.10 The use of a closed system can improve safety greatly.

Closed system devicesA closed-system transfer device is defined as: “a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system. The system must be airtight and leakproof”.11,12

The BD PhaSeal® system (Becton Dickinson) meets this definition and has been shown in several studies to diminish the contamination of working surfaces and reduce personnel exposure.13–15 However, less is known about the system’s capability to maintain product sterility in real practice.

The objective of this study was to evaluate the microbiological stability of products manipulated using the BD PhaSeal® system inside a biological safety cabinet. We also evaluated the system’s capability to maintain vial sterility once opened or reconstituted for an extended time and in different conditions.

MethodsThe cytostatic drug elaboration process was simulated using Tryptone soya broth culture medium instead of initial drug

“Hospital pharmacy departments provide ready-to-use cytostatic drugs and ensure that the physicochemical stability and asepsis of the product is maintained”

OncologyPharmacyPractice

Journal of

Original Article

Cost savings realized by use ofthe PhaSeal� closed-systemtransfer device for preparationof antineoplastic agents

Michael S EdwardsHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National

Military Medical Center, Bethesda, MD, USA

Dominic A Solimando JrOncology Pharmacy Services, Inc., Arlington, VA, USA;

Hematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National

Military Medical Center, Bethesda, MD

Franklin R GrollmanOncology Pharmacist, Hematology-Oncology Pharmacy Service, Department of Pharmacy,

Walter Reed National Military Medical Center, Bethesda, MD, USA

Janet L PangHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National


Ashley H ChasickHematology/Oncology Clinical Pharmacy Specialist, Ochsner Medical Center, New Orleans,

LA, USA

Charlene M HightmanHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National


Anthony D JohnsonHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National


Maxine G MickensHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National


Lorenzo M PrestonHematology-Oncology Pharmacy Service, Department of Pharmacy, Walter Reed National


Abstract

Purpose: Medication cost is a major factor associated with increasing health care costs in the United States.

Expenditures for prescription drugs in 2013 are estimated to be $283.7 billion. Closed system transfer devices are

widely used for preparation of hazardous drugs. Reports indicate the Phaseal� closed system transfer device maintains

Corresponding author:

Dominic A Solimando Jr, Hematology-Oncology Pharmacy Service,

Department of Pharmacy, Building 19, Room 3521, Walter Reed

National Military Medical Center, Bethesda, MD 20889, USA.

Email: [email protected]

J Oncol Pharm Practice

19(4) 338–347

! The Author(s) 2013

Reprints and permissions:

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DOI: 10.1177/1078155213499387

opp.sagepub.com

12


First author Groß (poster)24 Rowe25 Carey26

Study nameDown to the last drop - Comparison of drug retention volume of four transfer devices and resulting cost savings

Economic and microbiologic evaluation of single-dose vial extension for hazardous drugs

Second look at utilization of a closed-system transfer device (PhaSeal)

Method

Four different transfer systems were compared. The average retention volume/leftover in the vials was determined gravimetrically by weighing 20 ml vials empty, after filling with 10 ml of water and after withdrawal of the water using the four respective transfer systems.

Financial determination of SDV waste included 2 months of retrospective review of all doses provided. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trupticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD.

Non randomized, multi-center trial with interrupted time series design. Aliquots of sterile culture medium were transferred from test vials of sterile culture medium to IV bags of sterile medium over a 7-day time period. The IV bag test samples were then held under controlled incubation for 14 days, and monitored for evidence of contamination by an independent microbiology laboratory.

Results

Comparing BD PhaSeal and Mini-Spike Chemo Micro-Tip, potential cost savings using BD PhaSeal were 166,00 Euros including material cost. Including material cost, BD Phaseal was shown to induce additional expenses of 15,000 Euros compared to Chemo-Aide Clearlink.

The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at $766,000 annually, and tracking waste logs for these same medications was recorded at $770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process.

The results indicated that at the 168-hour mark, the probability of failure was 0.3%. In other words, at 168 hours, one would expect there to be a 99.7% probability that the vial would not be contaminated with bacterial growth if the same procedures were utilized under the same environmental conditions.


Due to its mechanical properties, the use of BD PhaSeal resulted in significantly smaller retention volume when compared to the other three spikes. Despite higher cost for the transfer device itself BD PhaSeal is a means for significant cost savings when preparing high-priced drugs.

The cost of discarding vials at 6 hrs was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represents exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than $600,000.

This study further demonstrates the BD PhaSeal system’s utility in extending the beyond-use date (BUD) and therefore reducing waste of viable pharmaceuticals. Extending the BUD results in improvements in the supply chain, beneficial effects on the environment, and significant cost savings for the healthcare system.

Journal name Wissenshaftticher Congress Journal of Oncology Pharmacy Practice American Journal of Pharmacy Benefits

Peer-reviewed No Yes Yes


ABSTRACT

Objectives: To assess the ability of the PhaSeal system to main-tain product sterility given current US Pharmacopeia Chapter 797 and International Organization for Standardization standards for use.

Study Design: Nonrandomized, multicenter trial with interrupted time series design.

Methods: Aliquots of sterile culture medium were transferred from test vials of sterile culture medium to intravenous (IV) bags of sterile medium over a 7-day time period utilizing the PhaSeal closed-sys-tem transfer device. The IV bag test samples were then held under controlled incubation for 14 days, and monitored for evidence of contamination by an independent microbiology laboratory.

Results: The results indicated that at the 168-hour mark, the probability of failure was 0.3%. In other words, at 168 hours one would expect there to be a 99.7% probability that the vial would not be contaminated with bacterial growth if the same procedures were utilized under the same environmental conditions.

Conclusions: Although the use of closed-system transfer devices has traditionally focused on reducing exposure of healthcare work-ers to hazardous substances, this study further demonstrates the PhaSeal system’s utility in extending the beyond-use date (BUD) and therefore reducing waste of viable pharmaceuticals. Extending the BUD results in improvements in the supply chain, benefi cial effects on the environment, and signifi cant cost savings for the healthcare system.

(Am J Pharm Benefi ts. 2011;3(6):311-318)

The Pharmacy & Therapeutics Society

Use of closed-system transfer devices (CSTDs) has

become an integral part of the processes associated

with preparation of hazardous medications. Tradi-

tionally, CSTDs have been used to reduce the amount of ex-

posure to hazardous medications experienced by healthcare

workers. However, 1 device in particular, PhaSeal (Carmel

Pharma AB, Goteborg, Sweden), has also been proved to

prevent contamination and potentially extend the beyond-

use date (BUD) of pharmaceuticals otherwise limited by

US Pharmacopeia Chapter 797 (USP <797>) sterility limits,

which has the potential to decrease waste.1 Decreasing

waste would not only provide signifi cant cost savings for

healthcare systems, but also assist with preventing wastage

of medications that are in critical short supply.

Healthcare costs in the United States continue to be an

area of great concern. Projections indicate that sometime be-

tween 2018 and 2020, the healthcare budget in the United

States will increase to more than 20% of the gross domestic

product. Traditionally, the rate of growth of drug expendi-

tures has exceeded the rate of growth of total healthcare

expenditures.2 In recent years, there has been equilibration

between the rate of growth of total healthcare costs and

the rate of growth of pharmaceutical costs. The Centers for

Medicare & Medicaid Services has projected a 5.2% growth

rate in overall healthcare expenditures in 2011. However,

clinic-administered antineoplastic agents have seen much

higher increases in cost growth. For example, there was

a 9.5% increase in costs between 2009 and 2010. As such,

there is tremendous potential in this area for signifi cant cost

savings.

At the same time that US healthcare costs are a concern,

there is also an increased focus on improving quality and

safety. To ensure patient safety associated with the use of

parenteral medications, USP <797> contains standards for

healthcare facilities to use as guidelines when preparing

compounded sterile products. Furthermore, USP <797> is

At a GlancePractical Implications p 312

Author Information p 317

Full text and PDF www.ajpblive.com

Second Look at Utilization of a Closed-System Transfer Device (PhaSeal)

E. Thomas Carey, PharmD; Ryan A. Forrey, MS; Douglas Haughs, BS; Dawn Moore Jefferson, PharmD; James A. Jorgenson, RPh, MS; Derek M. McMichael, PharmD; John M. Mulvaney, MHA; and Susan M. Spivey, PharmD, DDS

www.ajpblive.com Vol. 3, No. 6 • The American Journal of Pharmacy Benefi ts 311

Four different transfer systems were compared:

The average retention volume / leftover in the vials was determinedgravimetrically by weighing 20 ml vials empty, after filling with 10 ml of waterand after withdrawal of the water using the four respective transfer systems.For each type of transfer device, 30 vials were measured.

Down to the last drop – Comparison of drug retention volume of four transfer devices and

resulting cost savingsB. N. Groß1, K. F. Steiger1, M. J. Hug1, S. Kuhlendahl2

1Pharmacy, University Medical Center Freiburg, Germany, 2BD Medical, Germany

Introduction• In times of scarce resources and expensive treatments, the question arises whether and how drug therapies can be rendered more profitable. An approach to save

costs is to empty drug vials as completely as possible and thereby minimize discarded residues during the production process.• BD PhaSeal™ is a novel closed system transfer device claiming drug vial optimization due to its mechanical properties. It was shown to avoid aerosols more

effectively than other systems.1• We compared BD PhaSeal™ to three conventional spikes used in our pharmacy in terms of residual volumes and used these data to compute potential savings with

real-life consumption data of selected high-priced drugs.

Conclusions• Due to its mechanical properties, the use of BD PhaSeal™ resulted in a significantly smaller retention volume when compared to the other three spikes.• Despite higher cost for the transfer device itself, BD PhaSeal™ is a means for significant cost savings when preparing high-priced drugs.• In the present study drug retention volumes were based on only one particular vial size. Further investigations are needed to evaluate whether these results are

generally applicable.• Further investigations into the impact of the use of BD PhaSeal™ on factors such as waste disposal, process changes, preparation time, staff training and cleaning

time need to be conducted.

I. Comparison of retention volume

II. Potential cost savings

[email protected] F, Gorenc K, Lory W, Trittler R, Krankenhauspharmazie 2012;33:263 (Poster Wissenschaftlicher Kongress ADKA 2012)

Consumption data of the University MedicalCenter Freiburg of selected high-priced drugswas determined for the year 2013 and pricesper milliliter (AEK, purchase price) of thereconstituted vial were calculated. Drugswere chosen if fulfilling the following criteria:high-priced, sufficient shelf-life of the stock-solution for subsequent use, dose of vial notequivalent to dose most commonlyprescribed, no need for a filter-spike.

Potential savings were calculated bycomparing BD PhaSeal™ and the type ofspike predominantly used in our pharmacyfor certain drugs in daily practice.*

Comparing BD PhaSeal™ and Mini-Spike® ChemoMicro-Tip, potential cost-savings using BD PhaSeal™were 166,000 €including material cost.

Mean retention volume was significantly smaller with BD PhaSeal™ (0.25 ml) compared to Mini-Spike® Chemo Micro-Tip (0.64 ml, p < 0.0001, ∆ 0.39 ml), Mini-Spike® Chemo (0.42 ml, p < 0.0001, ∆ 0.17 ml) and Chemo-Aide Clearlink (0.29 ml, p = 0.0187, ∆ 0.04 ml).

BD PhaSeal™

Mini-Spike® Chemo Micro-Tip

Mini-Spike® Chemo

Chemo-Aide Clearlink 0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8 *******

Ret

entio

n Vo

lum

e (m

l)

BD PhaSeal™ Mini-Spike® Chemo(integrated 0.2 µm filter)

Chemo-Aide Clearlink

Mini-Spike®

Chemo Micro-Tip

Chemo-Aide ClearlinkDrug Cost per ml (€)

Pemetrexed 103Cetuximab 100 mg 12Cetuximab 500 mg 12Rituximab 34

Total of 3800 vials used in 2013

Including material cost, BD PhaSeal™ was shown toinduce additional expenses of 15,000 € compared toChemo-Aide Clearlink.

Mean retention volumes per vial (see I.) wereused to calculate the total discarded volumeper drug and the respective transfer device.Cost of the respective discarded volume wascalculated based on prices per ml (seetable).

* For some preparations a filter is mandatorywhich is embedded in Mini-Spike® Chemoonly. Therefore, the comparison of Mini-Spike® Chemo with BD PhaSeal™ was notcarried out in this cost analysis.

™

*

* Assumption of one transfer system per vial and additional cost of 5 €for BD PhaSealTM per vial

∆ 15,000 €

*

™

∆ 166,000 €

Mini-Spike® Chemo Micro-TipDrug Cost per ml (€)

Bevacizumab 100 mg 94Bevacizumab 400 mg 85PEG-liposomal Doxorubicin 61Trastuzumab 98Infliximab 60Panitumumab 106Total of 5880 vials used in 2013

®

13


First author McMichael27 DePrijck28 Vandenbroucke29

Study name Utility of the PhaSeal closed system drug transfer device

Microbiological challenge of four protective devices for the reconstitution of cytotoxic agents

Economic impact of the preparation scenario for cytotoxic drugs: an observational study

Method

Non-randomized trial with interrupted time series design. The PhaSeal closed system drug transfer device was applied to vials containing sterile culture media. The vials were entered using the PhaSeal system and samples were removed at 24, 78, 72, 96 and 128 hours. Samples were tested by an independent microbiology laboratory for evidence of contamination.

Four devices, i.e. Chemoprotect spike, Clave connector, PhaSeal and Securmix were challenged with low and high inocula of micro-organisms. The cells, transferred to the connected vials during repeated manipulations of the devices were counted by means of solid-phase cytometry.

In scenario one, discarded the residual fraction of the drug after each preparation. In scenario two, used the residual fraction of the vial until the end of the day. In scenario three, used the residual fraction of the vial until the chemical/physical expiry date. To analyze the economic impact of the three scenarios, looked at 3,086 preparations during July and August 2006.

Results

A failure rate of 1.8% was observed, which was not greater than expected. Secondary analysis of data was conducted based on time to failure. The analysis indicated that at the 168-hour mark there is a 98.2% probability that the vials will not be contaminated.

Of the four devices, PhaSeal afforded the lowest transfer of micro-organisms.

A major difference in cost was found between the three scenarios, namely; Euros 872,413, Euros 807,309, Euros 754,442 for scenarios one, two and three respectively. Savings varied between a minimum of Euros 52,867 (7%) and a maximum of Euros 117,971 (15%) for the observation period of two months, or an average of Euros 17 to Euros 38 per preparation.


The PhaSeal closed system transfer device does work to provide a mechanical barrier to the entry of contaminants into sterile solutions. Solutions could be expected to remain sterile for up to 168 hours.

Unlike aspects of operator protection, which are well-documented, the microbiological safety of protective devices for the preparation of cytotoxic drugs has not been addressed in the literature. This study estimates the susceptibility to microbial contamination during handling of four commonly used devices.

When cytotoxic medicines are prepared under rigorous conditions, pharmacists can contribute to substantial economic savings.

Journal name American Journal of Pharmacy Benefits Society of Applied Microbiology European Journal of Hospital Pharmacy



www.ajpblive.com Vol.3,No.1 • TheAmericanJournalofPharmacyBenefits 9

The Pharmacy &

Therapeutics Society

Utility of the PhaSeal Closed System Drug Transfer Device

Spending on healthcare in the United States contin-

ues to be a major concern. In 2008 the United Sates

spent $2.4 trillion on healthcare, which was 16.2%

of the total US gross domestic product (GDP).1 That fig-

ure rose in 2009 to $2.47 trillion, or 17.3% of the GDP. If

this trend continues unabated, projections are that spend-

ing will hit $4.4 trillion and top 20% of the GDP by 2018.2

This continued rise in spending puts extreme pressure on

all facets of the healthcare industry. Patients, their fami-

lies, providers, payers, hospitals, and the government all

feel the stress. Clearly, this situation is not sustainable and

everyone must work to reduce healthcare costs.

In organized healthcare settings, one of the fastest-

growing expense lines is prescription drugs. Drugs rou-

tinely consume 10% to 12% of total hospital expenditures,

and in some specialty hospitals such as cancer hospitals,

that amount is closer to 40% to 50%.3 With an average

cost of $800 million to bring a new drug to market, ad-

vances in treatment options come with a significant price

tag.4 Many of the newer drugs are large-molecule mono-

clonal antibodies. These drugs typically are parenteral

medications that come in single-use nonpreserved vials.

Current United States Pharmacopeia (USP) Chapter 797

standards mandate that nonpreserved or single-use drugs

must be discarded 1 hour after opening if that opening

occurred outside of International Organization for Stan-

dardization (ISO) 5 air conditions, or after 6 hours if the

vial was opened in ISO 5 air conditions and the drug re-

mained in those conditions for the entire time.5 This USP

standard was enacted to provide additional patient pro-

tection by minimizing the impact of any microbial con-

tamination of these products that could result in patient

harm. Even though these drugs are chemically stable, if

unused amounts are present after the stated USP standard

Derek M. McMichael, PharmD; Dawn Moore Jefferson, PharmD; E. Thomas Carey, PharmD; Ryan A. Forrey, PharmD, MS; Susan M. Spivey, PharmD, DDS; John M. Mulvaney, MHA; James A. Jorgenson, RPh, MS; and R. Douglas Haughs, BS

ABSTRACT

Objective:To assess theability of thePhaSeal closed systemdrug

transferdevicetopreventthecontaminationofparenteraldrugprod-

ucts,therebyallowingextendedbeyondusedating,whichcouldsignifi-

cantlyreducewasteandcostoftheseproducts.

Study Design: Nonrandomized trial with interrupted time series

design.

Methods: ThePhaSeal closedsystemdrug transferdevicewasap-

plied tovialscontainingsterileculturemedia.Thevialswereentered

usingthePhaSealsystemandsampleswereremovedat24,48,72,

96,and168hours.Samplesweretestedbyanindependentmicrobiol-

ogylaboratoryforevidenceofcontamination.

Results: A total of 1328 syringes were produced at 4 different in-

stitutions.Visual,microscopic,andmicrobiologicsubcultureanalyses

wereperformed.A failure rateof1.8%wasobserved,whichwasnot

greater thanexpectedandsupportedouralternatehypothesisat the

99%confidencelevelthatthePhaSealsystemiscapableofmaintain-

ingsterilityinacontrolledenvironment.Secondaryanalysisofthedata

wasconductedbasedontimetofailure.Theanalysisindicatedthatat

the168-hourmarkthereisa98.2%probabilitythatthevialswillnot

becontaminated.

Conclusion: ResultsofthisstudyshowthatthePhaSealclosedsys-

temdrugtransferdevicedoesworktoprovideamechanicalbarrierto

theentryofcontaminantsintosterilesolutions.Thestudydemonstrates

thatsolutionscouldbeexpectedtoremainsterileforupto168hours.

(Am J Pharm Benefits. 2011;3(1):9-16)

14

Date of publication 2012 2006 2004 2000

First author Sánchez-Rubio Ferrández30 Landini (poster)31 Poirier (poster)32 Ferencak (poster)33

Study nameUse of closed-stem drug transfer device (BD PhaSeal) and impact on preparation time

Implementation and standardization of a safety device for use in preparing and administering cytotoxic medications in an inpatient setting

Practical implementation of a closed system (PhaSeal) for the preparation, administration and disposal of cytotoxic drugs in a busy ambulatory cancer center

Implementation of safer chemotherapy systems utilized in a VA medical center

PurposeAssess the impact of the incorporation of PhaSeal on the processing time of chemotherapy.

Implementation of BD PhaSeal in pediatric and adult hospitals by a multidisciplinary stakeholder group.

Illustrate that a busy ambulatory centre could utilize a closed system for cytotoxic drug preparation, administration and disposal without a negative impact on its chemotherapy service.

To implement safer chemotherapy systems in a VA institution.

Method

Four experienced pharmacy technicians prepared six batches with each method simulating simple chemotherapy admixture operations. Compared the mean times obtained by student’s t test and evaluated the “learning effect” between days by ANOVA.

Smoothness of transition; pre-implementation wipe tests for cyclophosphamide.

Pharmacy and nursing staff were trained in the practical aspects of using PhaSeal. Evaluation form was completed three weeks into the trial by both pharmacy and nursing staff. Differences in preparation and administration times.

Pharmacy and nursing staff preparing and administering chemotherapy agents were in-serviced. After 60 days, surveys were taken to assess staff satisfaction. Staff were re-trained one on one if they were not satisfied with the new system.

Results

The average percentage of time saving compared to traditional technique of 31.7% was observed (time per batch [mean +/- SD] 6.44+0.73 vs 9.44+0.98 minutes).

Transition of BD PhaSeal into hospital went smoothly. Pre implementation wipe tests showed levels of contamination > 1ng/cm2 in some pharmacy prep areas.

By the end of week two, pharmacy and nursing staff were back to pretrial preparation and administration times.

There were no statistical differences between Pharmacy and Nursing employees. Employees who feel the new system is safer are likely to have used the system more than those who perceive the new system as not safer.

Implications

The BD PhaSeal system, in addition to its protective properties, is able to save time in the elaboration process which leads to efficiency in the pharmacy.

A multidisciplinary committee is essential to agree on hospital-wide protocols for cytotoxic drug handling.

The system reinforced the importance of the safety precautions that must be used during the handling of cytotoxic drugs.

Both nursing and pharmacy employees who regularly prepare or administer chemotherapy felt safer and were more satisfied with the PhaSeal chemotherapy system.

Journal name International Journal of Pharmacy Compounding

ASHP ConferenceJournal of Oncology Pharmacy Practice

ASHP Conference

Peer-reviewed Yes No Yes NA

Table 3 Studies evaluating the impact of CTSD implementation and efficiency

Previous studies have documented cytotoxic drug exposure in areas where staff prepare and administer these hazardous medications using the traditional open system technique. The open system technique can expose the handler through needle-stick, inhalation, and absorption through skin. Our ambulatory care and home infusion pharmacies were using a closed and needle-free system for preparing cytotoxic medications. PhaSeal® uses a double membrane closed system to ensure the leak-free transfer of drugs. Since employee safety is a concern, we wanted to implement this process in both our pediatric and adult inpatient hospitals. We also recognized the importance of standardizing the process across several areas to minimize the confusion for staff who work in both inpatient and outpatient areas as well as across hospitals (pediatrics and adults). The use of the PhaSeal® line heightens general awareness and alerts the health care professional to use precautions when handling the medication.

Phaseal® System

A committee composed of nursing and pharmacy stakeholders was formed to get input and involvement. This was a multi-disciplinary team comprised of staff nurses, staff pharmacists, technicians, pharmacy managers, clinical nurses, and nursing educators. We then arranged for the vendor to demonstrate the product to the members on the committee for familiarity with the product before making decisions. At the meetings, both nursing and pharmacy brought up concerns that were documented and addressed. Standardization with our ambulatory care setting and both inpatient settings was a goal in these meetings. A nursing lead was appointed to help address the nursing issues for both areas. Pharmacy addressed their concerns which included space, product stocking and allocation, minimizing compounds made in glass, additional staff during implementation, and issues with priming tubing. Decisions were made, a training process was set up, and work procedures were written in both nursing and pharmacy. The vendor training was scheduled for the whole hospital, wipe tests to check for pre-existing contamination were performed on nursing units and pharmacy satellites, and implementation dates were then negotiated and set.

We were able to standardize the process with all areas with only a few exceptions. Two weeks following training we implemented our project in the pediatric hospital. Pediatrics was chosen for the initial phase because of lower volume and fewer changes in pharmacy operations. Additional training was taking place in both pharmacy and in nursing simultaneously during this time to ensure that all users were trained and ready for the adult implementation date. Two weeks later we implemented in the adult hospital. The transition in both hospitals went smoothly with minimal issues and most of those issues were in regard to proper technique of the product.

Standardized Work ProcedureInput from all stakeholders is necessary to ensure that all aspects of handling are considered prior to implementation. We also learned that forming a multi-disciplinary committee is essential for successful implementation of standardized rules for cytotoxic drug handling. By addressing the issues of the stakeholders and with adequate planning, we were able to successfully standardize and change to the new system resulting in a safer work environment for all users.

The authors of this presentation have the following to disclose concerning current financial or personal relationships with commercial entities:

Kimberly Landini: Nothing to disclose

Stakeholders: What’s in it for them? Pharmacists • Personal safety

• Label creation easier and more efficient

Pharmacy Technicians • Personal safety • Possible increased efficiency around

manipulating hazardous chemicals • Allows for easier cross-training for

technicians to advance in the career ladder

Nurses • Personal safety • More efficient • Decreased use of glass so less

spills, and more consistency (i.e. one type of tubing)

Patients and Families • Personal Safety • Targeted exposure-no spills or drips

at bedside

Management • Increased employee and customer satisfaction

• Gain flexibility in scheduling

Implementation Plan Action Steps: • Initiate a work group of pediatric and adult nursing

representatives to agree on consistent delivery and preparation of these medications

• Bring in company representatives to demonstrate the product

• Develop work procedures • Product allocation from Materials and storage of

supplies for UH and Mott pharmacy satellites and nursing units

• Creation of chemo order group • Build and convert all chemos to IVPB route • Address total volume issues • Change most chemos from glass to plastic • Training for pharmacy and nursing • Roll out system in Mott (pediatrics) • Monitor progress and address concerns of

stakeholders • Roll out system in UH (adult) • Monitor progress and address concerns of

stakeholders

High levels of contamination of greater than 1.0 ng/cm2 were found in the pharmacy areas. Lower levels were found in the patient and nursing medication rooms.

Pre-Implementation Wipe Tests

The Protector with it’s expansion chamber is attached onto the drug vial. Upon puncture there is a membrane that prevents any air leakage. The expansion chamber captures any aerosols and vapors while maintaining equal pressure in the vial during drug preparation.

The Injector Luer Lock can be placed on a syringe for a dry connection during syringe filling and drug administration. Its encapsulated needle allows you to retrieve the drug from the vial and retracts into a “locked” position when procedures are complete to prevent any drug leakage or needle contact.

The Infusion Adapter is placed on the IV bag and provides a dry connection for spiking the administration set into the IV bag. It allows nurses the opportunity to select the tubing they need.

The Connector is used for attachment to IV lines for bolus administration and for sealed drug transfers from syringe-to-syringe.

www.phaseal.com

CONCLUSION

DISCLOSURE

RESULTS

Department Description Surface

Area Surface

(cm2) Total Volume

NaOH (ml) [CP] (ng/ml

NaOH) amount CP

(ng) CP

(ng/cm2)

8th floor Inpatient Pharmacy BSC Surface 5175 160 3.68 589 0.11

8th floor Inpatient Pharmacy BSC Airfoil 920 160 7.14 1142 1.24

8th floor Inpatient Pharmacy BSC Floor 4900 160 58.39 9342 1.91

8th floor Inpatient Pharmacy Checking Counter 2385 160 49.76 7962 3.34

Mott Pharmacy BSC Surface 6650 160 99.52 15923 2.39

Mott Pharmacy BSC Airfoil 1925 160 264.99 42398 22.03

Mott Pharmacy BSC Floor 4900 160 11.77 1883 0.38

Mott Pharmacy Checking Counter 3500 160 6.6 1056 0.3

8B Inpatient Chemobin Medroom 4482 160 0.11 18 0.01

8B Inpatient Floor Pat Room #8131-01 4900 160 18.02 2883 0.59

8A Inpatient Courtside Chemobin Medroom 5460 160 0.34 54 0.01

Inpatient Nursing 8A Room #8404 4900 160 0.35 56 0.01

7 Mott Floor left side Pat Room #7694-02 4900 160 15.36 2616 0.53

7 Mott Wall Medroom 4914 160 4.83 773 0.16

METHODSPURPOSE

University of Michigan Health System, Department of Pharmacy ServicesKimberly M. Landini, Pharm.D.

Implementation and standardization of a safety device for use inpreparing and administering cytotoxic medications in an inpatient setting

15

1. Simon N, Vasseur M, Pinturaud M, et al. Effectiveness of a Closed-System Transfer Device in Reducing Surface Contamination in a New Antineoplastic Drug-Compounding Unit: A Prospective, Controlled, Parallel Study. PLoS ONE. 2016;11(7):e0159052. doi: 10.1371/journal.pone.0159052.

2. Pasternak KM, Connell RM, Forrey R, Berdi F, Gonzalez R. Evaluation of syringe plunger contamination during hazardous drug preparation. Poster presented at: ASHP Conference; 2014.

3. Miyake T, Iwamoto T, Tanimura M, Okuda M. Impact of closed-system drug transfer device on exposure of environment and healthcare provider to cyclophosphamide in Japanese hospital. SpringerPlus. 2013;2:273. doi:10.1186/2193-1801-2-273.

4. De Ausen L, DeFreitas EF, Littleton L, Lustik M. Leakage from closed-system transfer devices as detected by a radioactive tracer. Am J Health-Syst Pharm. 2013;70:619-623. doi: 10.2146/ajhp110678.

5. Sessink PJM, Trahan J, Coyne JW. Reduction in Surface Contamination with Cyclophosphamide in 30 US Hospital Pharmacies Following Implementation of a Closed-System Drug Transfer Device. Hosp Pharm. 2013;48(3):204-212. doi: 10.1310/hpj4803-204.

6. Favier B, Labrosse H, Gilles-Afchain L, et al. The PhaSeal system: Impact of its use on workplace contamination and duration of chemotherapy preparation. J Oncol Pharm Practice. 2011;0(0)1-9. doi: 10.1177/1078155211401454.

7. Sessink PJM, Connor TH, Jorgenson JA, Tyler TG. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Practice. 2011;17:39-48. doi:10.1177/1078155210361431.

8. Nishigaki R, Konno E, Sugiyasu M, et al. The Usefulness of a Closed-system Device for the Mixing of Injections to Prevent Occupational Exposure to Anticancer Drugs. J Jpn Soc Hosp Pharm. 2010;46(1):113-117.

9. Siderov J, Kirsa S, McLauchlan R. Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Practice. 2010;16:19-25. doi: 10.1177/1078155209352543.

10. Yoshida J, Tei G, Mochizuki C, Masu Y, Koda S, Kumagai S. Use of a Closed System Device to Reduce Occupational Contamination and Exposure to Antineoplastic Drugs in the Hospital Work Environment. Ann Occup Hyg. 2009;53(2):153-160.

11. Jorgenson JA, Spivey SM, Au C, Canann D, Ritter H, Smith B. Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs. Hosp Pharm. 2008;43(9):723-727.

12. Nyman HA, Jorgenson JA, Slawson MH. Workplace Contamination with Antineoplastic Agents in a New Cancer Hospital Using a Closed-System Drug Transfer Device. Hosp Pharm. 2007;42(3):219-225.

13. Harrison B, Peters B, Bing M. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health-Syst Pharm. 2006;63:1736-1744.

14. Tans B, Willems L. Comparative contamination study with cyclophosphamide, fluorouracil and ifosfamide: standard versus a proprietary closed handling system. J Oncol Pharm Practice. 2004;10:217-223. doi: 10.1191/1078155204jp140oa.

15. Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003;60:2314-2320.

16. Spivey S, Connor TH. Determining Sources of Workplace Contamination with Antineoplastic Drugs and Comparing Conventional IV Preparation with a Closed System. Hosp Pharm. 2003;38(2):135-139.

17. Connor TH, Anderson RW, Sessink PJ, Spivey SM. Effectiveness of a closed system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health-Syst Pharm. 2002;59:68-72.

18. Nygren O, Gustavsson B, Ström L, Eriksson R, Jarneborn L, Friberg A. Exposure to anti-cancer drugs during preparation and administration. Investigations of an open and a closed system. J Environ Monitor. 2002;4:739-742. doi: 10.1039/b205132j.

19. Vandenbroucke J, Robays H. How to protect environment and employees against cytotoxic agents: The UZ Ghent experience. J Oncol Pharm Practice. 2001;6(4):146-152.

20. Sessink PJM, Rolf M-AE, Rydèn NS. Evaluation of the PhaSeal Hazardous Drug Containment System. Hosp Pharm. 1999;34(11):1311-1317.

21. Ho KV, Edwards MS, Solimado DA, Johnson AD. Determination of Extended Sterility for Single-Use Vials Using the PhaSeal Closed-System Transfer Device. J Hematol Oncol Pharm. 2016;6(2):46-50.

22. Sánchez-Rubio Ferrández J, Rodríguez Vargas B, Sánchez-Rubio Ferrández L, Lozano Estevan MDC, Iglesias Peinado I. CSTDs and microbiological stability of cytostatics. Hosp Pharm Eur. 2013;69:43-45.

23. Edwards MS, Solimando DA, Grollman FR, et al. Cost savings realized by use of the PhaSeal closed-system transfer device for preparation of antineoplastic agents. J Oncol Pharm Practice. 2013;0(0):1-10. doi: 10.1177/1078155213499387.

24. Groß BN, Steiger KF, Hug MH, Kuhlendahl S. Down to the last drop - Comparison of drug retention volume of four transfer devices and resulting cost savings. Poster presented at: Wissenshaftticher; 2012.

25. Rowe EC, Savage SW, Rutala WA, Weber DJ, Gergen-Teague M, Eckel SF. Economic and Microbiologic Evaluation of Single-Dose Vial Extension for Hazardous Drugs. J Oncol Pract. 2012;8(4):45e-49e. doi: 10.1200/JOP.2011.00488.

26. Carey ET, Forrey RA, Haughs D, et al. Second Look at Utilization of a Closed-System Transfer Device (PhaSeal). Am J Pharm Benefits 2011;3(6):311-318.

27. McMichael DM, Jefferson DM, Carey ET, et al. Utility of the PhaSeal Closed System Drug Transfer Device. Am J Pharm Benefits. 2011;3(1):9-16.

28. De Prijck, K, D’Haese E, Vandenbroucke J, Coucke W, Robays H, Nelis HJ. Microbiological challenge of four protective devices for the reconstitution of cytotoxic agents. Soc Appl Microbiol. 2008;47:543-548.

29. Vandenbroucke J, Robays H. Economic impact of the preparation scenario for cytotoxic drugs: an observational study. Eur J Hosp Pharm Pract. 2008;14(5):37-42.

30. Sánchez-Rubio Ferrández J, Lozano MC, Iglesias I, Sánchez-Rubio Ferrández L, Rodríguez Vargas B, Moreno Díaz R. Use of a CSTD (BD PhaSeal) and Impact on Preparation Time. Int J Pharm Comp. 2012;16(5);431-433.

31. Landini KM. Implementation and standardization of a safety device for use in preparing and administering cytotoxic medications in an inpatient setting. Poster presented at: ASHP Midyear Clinical Meeting; December 2006; Anaheim, CA.

32. Poirier S, Jones C, Calvert MJ. Practical implementation of a closed system (PhaSeal) for the preparation, administration and disposal of cytotoxic drugs in a busy ambulatory care centre. J Oncol Pharm Practice. 2004; 10(2).

33. Ferencak AH, Kopp MA, Hausermann DM. Implementation of safer chemotherapy systems utilized in a VA medical center. Poster presented at: ASHP Midyear Clinical Meeting; November 2000; Washington, DC.

References

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