Assessment of unintended volume loss of six closed system transfer devices

Abstract

<jats:sec><jats:title>Introduction</jats:title><jats:p> Closed system transfer devices (CSTDs) are used to prepare and administer hazardous drugs. Previous studies have explored the vapor and fluid containment performance of CSTDs. A less obvious consideration is the effect of CSTD use on the intended dose for small volume administrations. We assessed six CSTDs to determine if they contribute to volume loss and delivery of less than the intended dose during simulated drug administration. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Using an analytical balance, we obtained the mass of each CSTD at four points during simulated drug preparation and subcutaneous administration using sterile water. We used the masses to determine the average volume loss ( V<jats:sub>L</jats:sub>) for each CSTD. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Using ANOVA, we identified significant differences in volume loss ( V<jats:sub>L</jats:sub>) among the mean V<jats:sub>L</jats:sub> (F(6,59) = 18.45, p = 6.19 × 10<jats:sup>−12</jats:sup>) for the six CSTDs and control (no CSTD). Four CSTDs had a V<jats:sub>L</jats:sub> that was statistically different than the control (p &lt; 0.05); the V<jats:sub>L</jats:sub> for two CSTDs was not statistically different than the control (p &gt; 0.05). Volume loss did not depend on administration volume. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Volume loss performance varied among CSTDs. Volume loss may be clinically significant for small volumes but is not likely clinically significant for larger volumes. It is the authors’ opinion that 3 mL represents a reasonable administration threshold below which volume loss should be considered clinically significant. Users should consider volume loss in context of the tasks, drugs, users, and environments where CSTDs will be used. The United States Pharmacopeia (USP) General Chapter &lt;800&gt;: Hazardous Drugs–Handling in Healthcare Settings recognizes the lack of CSTD performance standards. USP &lt;800&gt; recommends independent performance evaluation of CSTDs based on peer-reviewed studies. Our study adds to the comparative performance evaluations of CSTDs available on the market at the time of this review. </jats:p></jats:sec>

Closed-system transfer device use with oncology biologics: A survey of Canadian healthcare practitioners

“…Similarly, if the sponsor is not aware that a CSTD is being used, a lack of efficacy due to patient under-dosing as a result of large residual volumes in the device, may be overlooked. For example, if an oncology biologic product’s maintenance dose is 420 mg (420 mg/16 mL vial) every three weeks and residual volumes of up to 1 mL can be lost within select CSTDs, 6 , 7 , 10 – 12 CSTD use could result in a loss of up to 26 mg of drug per dose at each visit. Therefore, patients treated with this regimen may experience progression of their disease earlier if they were treated at institutes that use CSTDs to prepare this product compared to those treated in institutes that use a traditional needle and syringe.…”

“…[6][7][8][9] First, CSTDs can leave a larger residual volume in the various components of the device system relative to a traditional needle and syringe, ranging from 0.7 to 1.0 mL, making the delivery of the total intended dose from small vials a challenge. 6,7,[10][11][12][13] Furthermore, though CSTDs are purported to provide HCPs a protective barrier from hazardous drugs, a lack of impact on the quality of biologics is yet to be demonstrated and therefore cannot be negated. 6,7 In addition, some CSTDs can introduce extrinsic particles into the drug product vials; particles resembling rubber fragments not visible to the naked eye upon CSTD use have been detected by micro-flow imaging.…”

Effectiveness of Closed System Drug Transfer Devices in Reducing Leakage during Antineoplastic Drugs Compounding

“…In another recent paper, Kulju et al also examined the hold-up volume, comparing the performances of the PhaSeal TM , Texium TM /SmartSite TM , OnGuard ® /Tevadaptor ® , Equashield ® , ChemoClave TM , and ChemoLock TM [35]. The authors established that the different CSTDs contribute to volume loss by using sterile water during simulated processes of drug preparation and subcutaneous administration in different measures.…”

Safe handling of hazardous drugs

“…Closed system drug-transfer devices are not a substitute for class II type B BSC. There is evidence from studies 24 – 48 that closed-system drug-transfer devices can reduce contamination during preparation and increase or extend the beyond-use date of a drug. Further emerging evidence suggests that when these devices are not used as specified, they could become open to the environment.…”