ICU MEDICAL SUPPORTING INFORMATIONThe role of Litmus testing using 5FU to evaluate Syringe Barrel
plunger contamination when using with a CSTD for preparation ofhazardous drugs
Data on File at ICU Medical, Inc.

Introduction
The risks associated with the compounding and administration of hazardous drugs (HD) have been evaluated anddocumented in several studies.1 The Occupational Safety and Health Administration (OSHA) and professional organizations
began promoting the adoption of safe handling guidelines starting in the mid-1980s. Several organizations and government
agencies in the US have published safe handling guidelines and standards for hazardous drugs, including the US
Pharmacopeia (USP).2,3 USP General Chapter <800> provides standards that require the use of a closed system transferdevice (CSTD) for antineoplastic HDs when the dosage form allows administration and recommend the use of a CSTD for
HD compounding when the dosage form allows.
Since the development of CSTDs, several options exist
USP <800> requires the use of a closed
for HD preparation and administration, as well assystem transfer device (CSTD) for HD
standardized ways to evaluate their efficacy of hazardous
drug containment. Some are being promoted today foradministration and recommend the use
their effectiveness by “closing all routes of exposure,”of a CSTD for HD preparation.
indicating multiple routes of clinician exposure tohazardous drugs.4 These routes include at the connection
point and the posterior (barrel) end of the syringe. It’s been suggested that having a proprietary syringe design that closes
off the syringe barrel (posterior end) ensures that all routes of exposure are closed, thereby providing a safer CSTDcompared to others on the market.

Background
One of the more widely accepted methods for evaluating surface leaks is using
Fluorouracil (5FU), in combination with litmus strips.5 With a standard pH rangeof 8.6 to 9.4, 5FU is easily recognizable on litmus strips that can detect pH levels
greater than 7. Using 5FU is preferred over other surrogate options because it is acommon hazardous drug that can be compounded in accordance with both thedrug’s instructions for use (IFU) and the CSTD’s intended purpose. There are
currently a limited number of published pH litmus studies that represent thecurrent CSTDs on the market, leaving users with a limited number of outdated
studies based on products no longer in the market.

ChemoLock™ CSTD on 5FU vial and BD
syringe, sterile water for wetting litmus

While the primary focus of litmus testing has been at the connection points of the CSTD, further evaluation of the syringe
component is warranted.

Objectives
The purpose of this white paper is to provide an analysis of the presence of residual hazardous drug on the inner syringe
barrel after multiple activations in a simulated compounding environment. A worst-case drug transfer model using
5 repeat transfers for 3 separate syringe, for a total of 15 each, with litmus detection following each activation, wasdeveloped to evaluate the ChemoLock CSTD. A litmus test is also a simple method to verify that the posterior (barrel)end of the syringe of a CSTD does not have liquid residuals following a simulated drug transfer procedure withmultiple activations.
Testing was conducted at ICU Medical, Inc., San Clemente, CA, in Class IV Biological Safety Cabinet as required by USP for
the compounding of hazardous drugs. Each CSTD system included a syringe adapter component ChemoLock™ injector
and a vial adapter with an access ChemoLock port.

Materials
To evaluate the risk of contamination associated with hazardous drug transfers using a standard syringe barrel,
ICU Medical chose Fluorouracil (5FU) as the challenge drug. Fluorouracil (5FU) is easily detected using standard litmus
strips with a pH detection of greater than 7 pH.5 The pH strips chosen to offer a single-color match at every 0.5 intervals
from pH 6.5–13.0 and a large test area making them easy to use.
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1 vial of Fluorouracil (5FU); 2.5 gm / 50 mL, Fresenius Kabi
Litmus testing strips; Micro Essential #9600, Lot number 203318U
30 mL standard BD luer lock syringes (3 count)
20 mL standard Monoject™ luer lock syringe (3 count)
One 18G needle attached to 5mL luer lock syringe
Sterile water
ChemoLock injectors (6 count); CL2000S, Lot number 4549307
ChemoLock vial spikes (6 count); CL-80S, Lot number 4179243

Methods
In this model, the litmus testing strips were wetted with sterile waterto enhance the uptake of 5FU surface residuals.
First, to process a positive control, 1 mL of the drug was removed
from the vial using an 18G needle attached to a 5 mL luer lock syringe.
Wet litmus paper was rubbed against the needle in which a bead of5FU was exposed.
A ChemoLock vial spike with the port was then attached to the 5FU
vial. A ChemoLock injector was attached to the vial spike, and 20 mL
of 5FU was withdrawn from the vial. The vial was stood upright on theBCS surface, and the 20 mL of 5FU was re-infused into the vial. TheChemoLock injector was disconnected from the syringe.

Left: ChemoLock vial adaptor and syringe adaptor
withdrawing 5FU. Right: Litmus testing inside syringe barrel

Results of the syringe barrel litmu testing show no detectable residual hazardous drug on the insidebarrel of common syringes used in the pharmacy.

The litmus paper was inserted into each syringe barrel, and the sidewalls of the syringe barrel were firmly swabbedto ensure the litmus paper contacted the 5FU. The selection of 5 transfers were selected to represent the worst-casescenario. All litmus touches within the syringe barrels were recorded in the results table and photographed for
documentation of results.
All functions were performed wearing nitrile gloves.

Results

Results of the syringe barrel litmus testing show no detectable residual hazardous drug on the inside barrel of common
syringes used in the pharmacy, suggesting that the syringeResults
piston clears the inner barrel of the syringe of residual
Results
Resultsof the syringe barrel litmu testing show no detectable residual hazard
Results
Results of the syringe barrel litmu testing show no detectable residual hazardou
hazardous drug during use.

barrelofofcommon
syringesusedin the pharmacy.
Results
the syringe
barrelused
litmu
show no detectable residual hazardou
barrelof common
syringes
intestingthe pharmacy.
barrel of common syringes used in the pharmacy.

BD 30 mL Syringe Study Results

SwabD/ND

Monoject 20 mL Syringe Study Results

SwabD/ND

A1

ND

D1

ND

A2

ND

D2

ND

A3

NDD3ND

A4ND

D4ND

A5ND

D5ND

B1ND

E1ND

B2ND

E2ND

B3ND

E3ND

B4ND

E4ND

B5ND

E5ND

C1ND

F1ND

C2ND

F2ND

C3ND

F3ND

C4ND

F4ND

C5ND

F5ND

Conclusions
The results of the study show that the use of the ChemoLock CSTD with standard BD and Monoject syringes demonstrated
no detection of 5FU hazardous drug presence within the syringe barrel following a worst-case simulated use model. The
use of wet litmus paper and a high pH drug, such as 5FU, is a simple and effective way to analyze the ability of a CSTD
syringe combination to detect presence of residual drug inside the barrel of a syringe.

References
1.

2.
3.
4.
5.

Centers for Disease Control and Prevention. National Institute for Occupational Safety and Health. Preventing Occupational Exposures toAntineoplastic and Other Hazardous Drugs in Health Care Settings: Hazardous Drug Exposure In Healthcare:https://www.cdc.gov/niosh/topics/hazdrug/effects.html
http://www.cdc.gov/niosh/docs/2004-165/
https://www.cdc.gov/niosh/docs/wp-solutions/2013-103/pdfs/2013-103.pdf
American Society of Health System Pharmacists Council on Professional Affairs. ASHP Guidelines on Handling Hazardous Drugs.
Am J Health-Syst Pharm. 2006;63:1172-1193
USP General Chapter <800>: Hazardous Drugs—Handling in Healthcare Settings. The United States Pharmacopeial Convention PharmacopeialForum (PF). December 2019
Comparative Study of Syringe Contamination by Hazardous Drug
Centers for Disease Control (CDC). Regulations.gov Comments from Firouzan Massoomi, Comparative Research Report Assessment ofClosed System Transfer Devices 5-FU Drug Leakage: https://www.regulations.gov/documentd?D=CDC-2015-0075-0027

Micro Essential Laboratory, pH Strips
https://microessentiallab.com/ProductInfo
5FU PIshttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55dbd7b2-f9f1-4863-82b5-d4d85bd5d28b
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0794add-67a7-4308-93e9-f889472716cc© 2024 ICU Medical, Inc.

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