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A Vapour Containment Performance Protocol for Closed System Transfer Devices (CSTDs) Used During Pharmacy Compounding and Administration of Hazardous Drugs (HDs) – a UK perspective on the draft NIOSH protocol.
IntroductionAlan-Shaun Wilkinson1,2, Michael Allwood2, Colin Morris1, Andrew Wallace1, Rebecca Finnis1, Ewelina Kaminska1,
Donata Stonkute1, Maja Szramowska1, Joe Miller1, Ian Pengelly3, Michael Hemmingway3.1Biopharma Stability Testing Laboratory Ltd, 2University of Derby, UK, 3The Health and Safety Laboratory (HSL), UK.
Get in touch [email protected] | [email protected] | www.biopharmatesting.co.uk
Biopharma Stability Testing Laboratory Limited, BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF
References[1] National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS) notice in the Federal Register in August, 2015 entitled “A vapour containment performance protocol for closed system transfer devices used during pharmacy compounding and administration of hazardous drugs”.[2] A. Wilkinson et al. Vapour Containment performance of CSTDs. Hospital Pharmacy Europe Summer 2016: volume 082, 25-32pp.[3] Employment Committee on the EU Strategic Framework on Health and Safety at Work 2014-2020, the European parliament called on the Commission to take action on chemical risk factors in the healthcare sector and to include specific provisions on healthcare workers’ exposure to hazardous drugs in the OSH strategic framework.
AcknowledgementThe authors wish to acknowledge the support of Ian Pengelly and Dominic Pocock of the HSL for their support and in auditing the BSTL research and quality systems that underpin this study.
In August 2015 the National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS) published a notice in the Federal Register – draft protocol “A Vapor Containment Performance Protocol for Closed System Transfer Devices (CSTDs) Used During Pharmacy Compounding and Administration of Hazardous Drugs”1.The protocol assesses vapour release when a CSTD is manipulated according to two pharmacy tasks which mimic clinical practice:• Task 1: Reconstitution of a drug solution and addition to an IV bag.• Task 2: Reconstitution of a drug solution and addition through a Y-site administration set representing a bolus injection or IV “push”.A CSTD is a device used to facilitate the transfer of drug from one reservoir to another, and may be used throughout the drug-handling chain from pharmaceutical compounding to patient dose administration. CSTDs are designed to reduce the opportunity for healthworker exposure to hazardous drugs either by exposure to aerosols, drug vapour or liquid release.2
Commercial CSTDs can utilize one of two approaches:(1) a physical barrier to prevent all mass from crossing the system boundary or (2) air-cleaning or a filter based technology. Figure 1. Figure showing the BSTL replica NIOSH experimental apparatus.
Figure 5. Figure showing real time IPA vapour release using the MIRAN and ppbRAE detectors under IFU with ICU Medical ChemoClave™ CSTD system.
Author Contact email: [email protected]
Results
Conclusions and the need for a Universal Vapour Test Protocol for CSTDs
Scientific Approach
1. NIOSH had non gas tight connection between chamber and MIRAN infra-red detector.2. NIOSH did not measure actual flow rate during testing – a critical parameter when measuring transient IPA concentrations as per NIOSH draft protocol.3. Poor sensitivity filter based infra-red detector LOD ~0.3ppm and LLOQ 1ppm. We added a ppbRAE detector.4. NIOSH did not operate CSTD systems according to manufacturer’s instructions for use (IFU).5. Unsuitable surrogate selection, 70% Isopropyl alcohol (IPA): water mixture. Vapour pressure of IPA is 4400 Pascal, ~106 higher than one of the most volatile hazardous drugs (HD) to have its vapour pressure determined – Carmustine (0.019 Pascal). Figure 4. Figure showing IPA concentration versus MIRAN detector response
under “closed loop” operation.
The draft NIOSH protocol as written only provides performance data on physical barrier CSTDs and is unsuitable for use with CSTDs that employ air filtration technology due to the choice of surrogate.2016 Warning from European Strategic Framework Policy - some manufacturers CSTD equipment fall short of the requirements for preventing aerosols, vapour release and liquid spillage3.
“ICU Medical ChemoClave™ exhibits leaky behaviour under BSTL testing”.
Table 1. Table showing CSTD performance according to the BSTL IFU NIOSH vapour test.
Full study data published in Hospital Pharmacy Europe 20162. The data from the ChemoClave™ CSTD (marketed by ICU Medical) highlights the need for independent evaluation of all commercially available CSTD systems prior to use for pharmacy compounding and administration – this CSTD was found to give the highest IPA release under test for a physical barrier CSTD.
“The draft NIOSH protocol is designed to test the performance of physical barrier type CSTDs only. There is therefore a need for a single Universal Vapour Performance Test Protocol applicable to all types of CSTD allowing an evaluation of vapour containment under identical test conditions.”
Miran IPA concentration (ppm)
Theo
reti
cal P
A c
once
ntra
tion
(ppm
)
0.0 20.0 40.0 60.0 80.0 100.0
120.0
100.0
80.0
60.0
40.0
20.0
0.0
If IFU conditions are not used for all manipulations of CSTD systems, as in the NIOSH draft protocol CSTD function is compromised. Isopropyl alcohol is a poor surrogate for HDs and inappropriate due to its extremely high vapour pressure. This causes problems with most administration equipment due to chemical incompatibility.
Time from Start of Task (seconds)
IPA
Con
cent
rati
on (p
pm)
0 500 1000 1500 2000 2500
6.0
5.0
4.0
3.0
2.0
1.0
0.0
MIRAN ppbRAE
Figure 2. Isopropyl alcohol.
Figure 3. Carmustine.
Task CSTD DeviceNumber of BG-0max
observations (N)
Mean of BG-0max
observations (ppm)
Lower 95% Confidence Limit (ppm)
Upper 95% Confidence Limit (ppm)
Standard Deviation
(StDev)(ppm)
1
2
2
Carefusion Smartsite®
/Texium®
ICU Medical ChemoClave™BD Phaseal™Tevadaptor®
Carefusion Smartsite®
/Texium®
ICU Medical ChemoClave™BD Phaseal™Tevadaptor®
†Tevadaptor® with 1% IPA
5
5
55
5
5
55
5
1.5
3.8
0.47.4
1.1
2.7
0.59.0
0.2
0.0
1.5
0.36.2
0.6
2.2
0.58.9
0.1
2.9
6.1
0.48.6
1.6
3.1
0.59.0
9.0
0.9
1.8
0.11.0
0.3
0.4
0.00.1
0.1
Analysis variable: BG-0max
“The liquid release is seen easily
by eye and this correlates with the chemical
vapour detection values for
IPA release.”
y = 1.0424x – 0.5452R2 = 0.9989
BSTL identified a number of scientific drawbacks with the NIOSH draft protocol and after constructing a replica test system (figure 1) tested the same CSTDs using a modified NIOSH protocol correcting the following deficiencies:
† 1% IPA in water was chosen as a more representative challenge agent having a vapour pressure of 44 Pascal. This resulted in a 50 fold reduction in vapour release.
