WHITE PAPER

Accuracy Evaluation of the Diana ™ Compounding
Workflow System

BACKGROUND
The Diana compounding workflow system, manufactured by ICU Medical Inc., is the world’s first needlefree, user-controlled
automated sterile compounding system for the accurate, safe, and efficient preparation and reconstitution of hazardous
drugs. Today, our next-generation, USP <800>-compliant system combines tablet-based IV workflow and innovative
automation to keep clinicians and patients safe from hazardous drug exposure to chemotherapy preparations, and prevent
accidental needlesticks. The system also safeguards the drugs themselves, thanks to a microbiologically and mechanicallyclosed design, which protects the preparation from exposure to environmental contaminants.

PURPOSEThis study was conducted to evaluate the accuracy of the Diana system in a live pharmacy environment in order to verify thatthe system’s fluid-dispensing accuracy was within the manufacturer’s stated accuracy claim for volume measurements (±5%error above 5 mL). This study examined data gathered from preparations that required multiple vials, as well as preparationsof a selection of drugs commonly prepared in the pharmacy.

INTRODUCTION
The process of measuring medication during the compounding of intravenous medications has inherent variables.
Syringe volume graduation markers have been shown to vary by up to ±5%.1 Human precision in reading the syringe submarking measurement is generally considered to be ≥ ±1 mL for fluid volumes drawn in syringes with capacity ≥ 20 mL.2
Additional human factors such as interruptions, fatigue, and memory lapse are recognized in clinical literature to contributeto preparation errors.2,3 Finally, manufacturers' diluent IV bags are consistently overfilled, and the overfill varies between
the lot numbers of the manufactured products. The standard allowable variation in manufactured pharmaceuticals andcompounded preparations is 90 to 110% of the active ingredient.4,5,6,7 However, because of these combined factors, researchsuggests that “across the country, 9 of every 100 IV doses that require compounding in the pharmacy contain one or moreerrors when they are delivered to the nurse.”8As a result, the final compounded preparation can inadvertently be out of specification and not meet the required standards.
These variations may also contribute to an admixture that differs from the physician-ordered prescription, potentiallyaffecting small therapeutic window situations or contributing to unnecessary drug waste. The Diana compounding workflow
system helps take the variation out of the manual drug preparation practice to create an accurate, reliable, and repeatablesterile preparation and safe-handling process.

SYSTEM OVERVIEW
The next-generation Diana system is a syringe pump module controlled by a high-precision stepper motor that facilitatessmall- and large-volume medication transfers. The system uses ICU Medical’s proprietary closed system, fluid transfercomponents to help reduce exposure to hazardous drugs while preserving the sterility of the preparation. ICU Medical
publishes its accuracy specification at the first standard deviation (SD). This means that 68% of the data set will be within
the published accuracy range. It also means that 95% of the data set will be within two times the published accuracy range.
The Diana module uses a 20 mL syringe cassette with an integrated stopcock, which can manage the fluid path from theinput container to the output container. The cassette technology system can feature either two ChemoLock™ or two Spiros®
needlefree closed male luers to facilitate drug transfer between the drug manufacturer’s vial and the IV bag or other maleluer device connected to the patient IV container.
The Diana system removes the need for gravimetric components to obtain an independent accuracy assessment, a processthat can be difficult to maintain due to specific gravities of drugs. Rather, the system provides three methods for independent
verification of accuracy: photographic, volumetric, and proprietary sensor technology based on the simultaneous use of astepper motor and fluid sensor. The stepper motor knows the position of the syringe plunger at all times (both drawing andpulling). While the syringe plunger is pushing, the sensor identifies the presence of fluid. The sensor can detect the presenceof fluid over 700 times per mL, allowing the system to accurately monitor the volume of fluid pushed. These independent
systems work in concert with each other to provide a system that can effectively and accurately transfer hazardous drugs,
with the use of gravimetric scale.

METHODOLOGY
A compounding log from a leading cancer center was obtained to provide data on the accuracy of the Diana system, andclinical volumes were identified for the following drugs:> Paclitaxel		> Fluorouracil		> Etoposide> Cisplatin		> Methotrexate		> Carboplatin

TEST PROTOCOL
A test protocol was created to perform medication transfers using the Diana system at clinically relevant volumes to determine
system accuracy. The specific gravities of the drugs were obtained, and a scale was used to manually determine accuracy(ICU Medical DS2000).
6. Initiate the transfer
1. Assemble the components:> Attach a new Diana cassette to the Diana syringe pump module
7. Place the bag on the scale> Attach a bag spike to the empty bag
8. Record the weight> Attach an ICU Medical vial adapter
9. Determine the actual volume dispensed 		
2. Place the empty container on the scale and press tareby applying the specific gravity to the 		
3. Attach the components to the Diana syringe pump module
weight measurement
4. Enter the transfer information into the Diana system
10. Analyze the resulting data
5. Record the photos of the drug vials

TEST RESULTS
The Diana system performed better than the published accuracy specifications within all accuracy ranges (Figure 1). The
overall average accuracy of the data was 0.8% with a standard deviation of 0.92%, well within the acceptable range of ± 10%
as dictated by USP <797> and within the stated accuracy claims of ± 5%.
Figure 1. The accuracy of the Diana system at clinical volumes+10.0%
+8.0%
+6.0%
+4.0%
+2.0%
0.0%
-2.0%

02040

60

80

100120140160

180

200

-4.0%
-6.0%
-8.0%
-10.0%
Diana Transfer

Average+STDEV-STDEV

Accuracy of Preparations by Drug TypeThe Diana system provided consistent accuracy when preparing each of the six drugs tested. Drugs with low volumes of data(< 10 data points) had higher average accuracy; however, it is expected that if additional data points were captured, Diana
would have displayed performance closer to the average performance across all drugs. Each specific drug had an averagevolume and accuracy of the following:
Drug Type
Paclitaxel
Carboplatin
Cisplatin
Fluorouracil
Etoposide
Methotrexate

Average Volume28.36
32.97
95.44
82.519.47
9.19

Accuracy
0.4%
0.9%
0.2%
1.2%
1.6%
1.0%

Accuracy of Displayed Volume vs. Actual Volume
When compared to actual volumes, the displayed volume of the Diana system has a high degree of correlation (Figure 2.) The
data indicates that the displayed volume of the transfer does in fact meets the actual volume delivered.

Figure 2. Displayed volumes vs. actual volumes
y= 1.0051 x +0.0669

Dipslayed Volume (mL)

20015010050050

100

150

200

Actual Volume (mL)Diana Transfer

CONCLUSION
The Diana compounding workflow system was shown to provide accurate compounding of chemotherapy drugs.
When preparing a variety of common drugs, the system’s performance fell within established guidelines of ± 10% and thedevice’s published accuracy specification at the first standard deviation (SD). While this study demonstrates the Diana
system’s ability to provide consistent accuracy, it is still important to utilize a product trial before implementation to properly
gauge the performance of the Diana system and ensure compatibility with site-specific drugs and workflows.

REFERENCES
1. http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=14835
2. http://www.usp797.org/QA-E25.htm
3. http://www.ashpmedia.org/advantage/2cpe/compounding/handout_compounding_ondemand.pdf
4. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c795.html
5. http://www.medscape.com/viewarticle/772269
6. http://www.cnn.com/2012/10/08/health/throwing-away-expired-meds/index.html
7. http://www.ashp.org/DocLibrary/Bookstore/P2074/Chpt-15.aspx
8. Flynn EA, Pearson RE, Barker KN. Observational study of accuracy in compounding i.v. admixturesat five hospitals. Am J Health Syst Pharm 1997 May 1;54(9):1110.

©2017 ICU Medical Inc.

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