ICU M ED IC A L SU P P O RT ING INF O R M AT IO N

ChemoClave™ Closed System Transfer Device (CSTD)
Surface Wipe Study Using Methotrexate (MTX) as a Marker
Report of a study commissioned by ICU Medical Inc. and conducted by and at RJ Lee Group, Inc.,
Greene County, PA

Background
ChemoClave is a needlefree closed system drug transfer device that meets the definition recognized by USP <800> as “a drugtransfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escapeof the hazardous drug or vapor concentrations outside the system.”1,2 To validate a CSTD’s ability to “prohibit the escape of
hazardous drug concentrations outside the system,” surface wipe test methods have been developed and commissioned
by ICU Medical Inc.
The US Food and Drug Administration (FDA) accepts surface wipe studies as part of the 510(k) premarket clearance for closed
system transfer devices. Surface wipe test results are included in the documentation submitted to the FDA to obtain 510(k)clearance for the ChemoClave (K173477) CSTD with the following indications for use: The ChemoClave is a needlefree Closed
System Transfer Device (CSTD) that mechanically prohibits the transfer of environmental contaminants, including bacterial andairborne contaminants into the system, and the escape of drug or vapor concentrations outside the system during drug
preparation and administration, thereby minimizing exposure of individuals, healthcare personnel and the environment tohazardous drugs.3

Objective
The purpose of the surface wipe study was to evaluate the ChemoClave CSTD for containment of hazardous drugs through asurface wipe analysis while performing compounding tasks using methotrexate as the hazardous drug marker.

Methods
The study was conducted at RJ Lee Group (RJLG) laboratory, where all tasks were performed in a Class II biological safetycabinet (BSC) in a Class 100 cleanroom. Before the study, four (4) separate surfaces of the BSC work area, measuring
approximately 400 centimeters squared (cm2) were demarcated: two (2) separate surfaces of the BSC workbench (left andright of middle); the BSC grill (middle); and the BSC airfoil (middle).

Hazardous Drug Marker
Methotrexate was selected as the hazardous drug marker for its common use in the clinical setting and the availabilityof a sensitive analytical method to detect trace levels of the chemical. Vials of liquid MTX for injection, USP, 1 g/40 mL(Teva, Pharmaceuticals, Lot.13F21KA) were acquired for the study.

Pre-study
MTX vial decontamination
To minimize the concern that vial contamination could impact the study, all MTX vials were decontaminated and tested before
use. The multi-step decontamination procedure was intended to deactivate and remove traces of MTX from surfaces. The
procedure included separate applications of detergent containing sodium hypochlorite and sodium thiosulfate/benzyl alcohol
followed by wiping with lint-free towels and rinsing. After drying, composite wipe samples were collected from vials, and theresults were obtained to verify that no detectable levels were present.

BSC decontamination
Before each CSTD evaluation, the demarcated work area surfaces within the BSC were decontaminated using the proceduredescribed above for the vial decontamination, and wipe samples were collected from the BSC workbench (left and right), grill,and airfoil.

Training of CSTDs
A certified pharmacy technician performed all simulated compounding tasks using personal protective equipment (PPE) andwas trained in the use of the CSTD system following the system’s directions for use (DFU).

Sample Size
The study evaluated three (3) individual trials of the ChemoClave CSTD, where the CSTD
was accessed multiple times. The sample size represents the practice of normal hazardous
drug compounding procedures and is in alignment with the FDA’s review for hazardous
drug containment for CSTDs with the ONB clearance.

Field Blanks
Field blank samples were collected for quality control purposes.

Procedure

Photo 1. ICU Medical ChemoClavesystem, vial access.

For the CSTD system evaluation, three (3) individual trials were performed. For eachindividual trial, the pharmacy technician donned a new pair of nitrile outer gloves andperformed all compounding activities inside the BSC within the demarcated areas. The
technician placed four (4) IV bags, each containing 0.9% sodium chloride solution withthe CSTD on the BSC workbench with the access ports inside the demarcated area (twoon the left side and two on the right side). Four (4) vials of MTX were placed within thedemarcated area and accessed using the compatible CSTD.
One by one, the technician would draw off three (3) individual volumes of 12 mL of MTX
drug from each of four (4) vials and then push them into an IV bag, disconnecting andreconnecting after each individual transfer. During each trial, four (4) vials were used foreach of the four (4) IV bags, totaling 12 transfers, 144 mL, and 3.6 grams (g) MTX. The
simulated compounding procedure was completed in accordance with the CSTD
Instructions for Use.

Photo 2. ICU Medical ChemoClavesystem, IV bag access.

Following each trial, wipe samples were collected from each of the pre-determined wipe
locations using wipe sampling media (kits) assembled by RJLG. All samples were collectedby a Certified Industrial Hygienist (CIH) with RJLG following standard techniques using thewipe sampling media (kits) assembled by RJLG.
The samples obtained during the study were stored at or below negative 70°C before
laboratory analysis.
Following each trial, wipe samples were collected from the following locations:Technician’s gloves
BSC workbench left and right
BSC grill
BSC airfoil

Photo 3. Wipe sample collected fromBSC workbench (left).

Analysis
The wipe samples were prepared and analyzed according to internal proprietary methods using a liquid chromatograph thatwas equipped with dual-mass spectrometers (LC-MS/MS). Samples were processed at the laboratory in compliance with Good
Laboratory Practice (GLP) protocols (ref. 21 CFR Part 58) and Primera’s Bioanalytical Method Validation Standard Operating
Procedure SOP-PASC-0501. The laboratory analysis Limit of Quantitation (LOQ) was 10 nanograms (ng) per sample. For surface
wipe samples, the results were reported as ng per centimeter squared (cm2).

Data Analysis Provided byLaboratory Analysis Provided by

RJ Lee Group, Inc.
350 Hochberg Rd
Monroeville, PA 15146 USA

Primera Analytical Solutions Corp.
259 Wall Street
Princeton, NJ 08540 USA

Table 1. Summary of ICU Medical ChemoClave Trials
Sample ID
5297661

Surface
Field blankArea, cm2na

MTX, ngndMTX conc., ng/cm2
na52976625297663

Workbench left400

nd<0.025Workbench right

400

nd

<0.0255297664

Grill

400

nd

<0.0255297665

Airfoil400

nd<0.0255297666

Gloves–ndna

5297668

Workbench left

400

nd

<0.0255297669

Workbench right

400

nd

<0.0255297670

Grill

400

nd

<0.0255297671

Airfoil400

nd<0.0255297672

Gloves–ndna

5297673

Workbench left

400

nd

<0.0255297674

Workbench right

400

nd

<0.0255297675

Grill

400

nd

<0.0255297676

Airfoil400

nd<0.0255297677

Gloves–ndna

5297678

Workbench left

400

nd

<0.0255297679

Workbench right400

nd<0.0255297680

Grill400nd<0.025

5297681

Airfoil400

nd<0.025na – not applicablend – not detected (<10 ng/sample)

Comments

Decontamination,Pre-Trial Sampling

ChemoClave, Trial 1

ChemoClave, Trial 2

ChemoClave, Trial 3

Results
Data provided according to an analytical report from RJLG show the wipe samples collected from vials following the initial
decontamination procedure and before use in the study were free of detectable MTX. MTX was not detected on any of thesurface samples obtained before any of the work trials. Following trials with the ChemoClave CSTDs, no MTX was detected
on any of the working surfaces or the technician’s gloves.

Conclusion
Results of the surface wipe study suggest the ChemoClave CSTD was effective in preventing detectable surface contamination
during three separate trials of simulated compounding activities with known amounts of methotrexate.

References
1.

The United States Pharmacopeial Convention. USP General Chapter <800> Hazardous Drugs – Handling in Healthcare Settings. Chapter 14
Administering. 2017.

2.

National Institute for Occupational Safety and Health (NIOSH): A Performance Test Protocol for Closed System Transfer Devices Used During
Pharmacy Compounding and Administration of Hazardous Drugs. NIOSH Docket Number 288-A.

3.

U.S. Food and Drug Administration (FDA): https://www.accessdata.fda.gov/cdrh_docs/pdf13/K131549.pdf. Accessed January 20, 2023.

Surface Wipe Study Funded by ICU Medical Inc.

© 2023 ICU Medical Inc.

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