Hazardous drug use has been ubiquitous in oncology practice for decades with the majority of these drugs being administered intravenously and requiring reconstitution, dilution, and transfer to IV bags or administration directly to the patient via syringe injection. While hazardous drugs may effectively treat cancerous tissue, they also may damage healthy organs, and consequently can be hazardous to health care workers involved in their handling, preparation, and/or administration. Therefore, safe handling of hazardous drugs is critical to ensure the health of hospital pharmacists, nurses, and others who may come into contact with these medications.

The concept of using a device specifically designed to protect health care personnel handling hazardous drugs was introduced in 1999, when the first US article was published demonstrating the containment of hazardous drug drips, sprays, and vapors with a closed system drug-transfer device (CSTD).¹ The device was described in the following manner: “The system prevents leakage of drug into the environment, thus protecting health care workers from potential exposure to the drug being handled.” The containment of the CSTD was further validated by large, multi-center studies published in 2002 and 2003.^2-4 Then in 2004, NIOSH issued an alert stating that hospitals should consider adding CSTDs to comprehensive hazardous drug safety programs, and broadened the description of the CSTD to: “A drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system.”⁵ Fifteen years of data ultimately culminated in 2014, when the US Pharmacopeia validated the necessity of integrating a CSTD into the safe handling of hazardous drugs in proposed USP Chapter <800>: Hazardous Drugs—Handling in Healthcare Settings.⁶ The chapter recommends the use of a CSTD during compounding and mandates their use during drug administration.

With the introduction of USP <800>, the integration of CSTDs into hazardous drug safety programs is at a pinnacle point, due largely to the legacy of investigation focusing on the occupational risks of hazardous drug exposure to health care providers by pioneering investigators (see Suggested Reading List of Seminal CSTD Studies and Reviews at the end of this article). 

As clinical studies continue to validate the increased safety benefits to health care workers from CSTD use during drug preparation and administration, acceptance of these devices has risen commensurately (see TABLE 1). The development of CSTDs is an evolutionary step toward ensuring safety, and as a result, CSTDs have now made their way into mainstream practice as a key component for protection. As such, a comprehensive understanding of the development considerations and specific features of the available CSTDs is necessary to gain perspective when examining which device will best fit the needs of a given organization.

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Key Features of CSTDs
CSTDs available in US hospitals comprise a variety of features; examining the advantages and disadvantages of these characteristics allows health care providers to identify the components of the preferred device. While utilizing a single CSTD that satisfies the needs of pharmacy and nursing is ideal, and this approach also helps control inventory and training costs, combining more than one device to meet the needs of both clinician groups—provided the system remains closed—is acceptable, and certainly a significant improvement over one group using no device at all. 

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TABLE 2 summarizes the characteristics of each CSTD to consider when choosing a single CSTD or multiple devices.

Containment
The primary purpose of CSTD use is to ensure containment of hazardous drugs. Containment of spills, sprays, and vapors has been demonstrated in studies that incorporate fluorescence, pH/Litmus paper, water, and the use of titanium tetrachloride. Vendors’ approaches to containment vary, incorporating one or more of the following systems: filtration, sealed expansion chamber, sealed diaphragm, and/or compartmentalization. 

Pressure Equalization
How the device equalizes pressures between the vial and the CSTD is an important consideration. Pressures vary between vial lots and different manufacturers. Consider also the impact of manipulating drugs with the chemical characteristic of vaporizing as the atmospheric pressure at varying altitudes could cause variances. In addition, drug volume displacement can lead to variations of pressure within the system. Note whether outside air enters the system as part of the process or if the system adjusts in a closed manner via diaphragm and/or compartmentalization. 

Syringe Safety Features
During the compounding and administration process syringes can accidentally or purposely be disengaged from the syringe CSTD device. Manufacturers have built into their systems preventive design features to protect against the system being opened, including one-way engagement, reverse spinning function (PhaSeal), break-away once engaged resulting in spinning (ChemoLock, ChemoClave, Spiros), and pre-bonded devices (Vialshield and Equashield). It is important to note that in most cases, these systems cannot be opened with ease once closed for safety purposes. Thus, the need to open the system for special compounding and administration processes must be considered prior to using the system in specific scenarios.

Device-to-Vial Interface
Because vials for hazardous drugs come in a variety of sizes, it is important to consider the following attributes: vial sizes range from 1 mL to 100 mL; vial neck sizes range from 13 mm to 28 mm; and depth of the vial from the top of the vial to the bottom also must be considered. All of the current CSTD manufacturers have addressed vial neck diameters; however, not all have addressed the overall depth of the vial to the size of the spike of the CSTD. Ease of entry of the CSTD vial spike into the variety of vial stopper materials should be considered and explored to minimize spiking errors due to the varying thicknesses and shapes of vial stoppers. PhaSeal offers a manual assembly fixture that sits inside the biological safety cabinet or compounding aseptic containment isolator, and can be used to ensure simple, consistent attachment of the CSTD vial spike to a drug vial. Vial spikes of the CSTD can be a metal needle or plastic spike. (Note: Refer to manufacturer for incompatibility of CSTDs with specific drugs.)



Device-to-Device Interface
Device-to-device interfacing of CSTDs may occur either by membrane-to-membrane design that engages a needle (or needles) for the transfer of drug and vapors (see FIGURE 1), or a needle-free membrane-to-membrane design that opens a common channel for the transfer of drug and vapor (see FIGURE 2). The ability of the device-to-device interface to eliminate spill/spray and vapor is contingent on the tightness of the seal between components and the ability to demonstrate transfer without contaminating the outer surfaces of membranes. The system should completely seal at each point of contact prior to exposing the surfaces of the CSTDs to the environment during the separation of device components.

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CSTDs may incorporate a needle for the vial spike and for the device-to-device interface. In most cases, CSTD manufacturers have gone to great lengths to minimize the potential of needle exposure outside of the system. However, device failures can lead to needles being exposed; thus, it is vital to educate and train staff on the potential risks. Needle-free design ensures the user is not exposed to needles, eliminating the risk of needle-stick injury. 

User-to-Device Interface
A system that is intuitive to use with minimal opportunity for variation is ideal. Consider the perceived ease of use of a needle and syringe and open-ended IV lines; the CSTD system should be no more labor intensive. Practice sites that compound and administer one dosage to numerous patients per day, in particular, will benefit from such a system. Factors that impact the user’s interface with the system include: 

• Ease of removal of devices from manufacturers’ wrapping
• The number of components, the number of steps required for compounding, and the number of steps required for administration
• Simplicity of adding vial adapters to vials
• Minimized twisting or bending at the wrist, and minimizing manipulation of device components
• Ease of reconstituting powders and transferring fluid between device components 
• Tactile and/or visual confirmation of system engagement 

Concern about repetitive strain injury is warranted, especially for high-volume sites. Each of these features should be considered to ensure consistency in training and to reduce the risk of repetitive stress injuries. 

Pre-bonded Components
Pre-bonded components—syringes pre-bonded to CSTDs or IV tubing sets with pre-bonded, closed terminal ends—add efficiency and enhance the safety of a CSTD system. Pre-bonding can decrease time required for unpacking multiple components and ensure device engagement. In addition, pre-bonded devices decrease the potential to (accidentally or purposely) circumvent safety process during the compounding and administration of hazardous drugs. 

Integration with IV Delivery Systems
Integration of CSTDs with other IV delivery systems provides additional ease of use; thus, a device’s compatibility can be an important consideration. Reflect on how the device will integrate with existing equipment and workflow while simultaneously reassuring the user that the system is properly connected and closed. Currently, ICU Medical’s ChemoClave system that includes Spiros integrates with the Clave IV system and Spiros’ standard ISO connection is compatible with other needle-free connectors. Likewise, both Carefusion’s VialShield and Alaris pump tubing integrate with SmartSite/Texium. All CSTD manufacturers offer additional components to ensure integration with all current IV delivery systems.

CSTDs at the Bedside
When choosing a CSTD, it is vital to include nursing in the evaluation process to ensure seamless integration in both medication preparation and administration. Nursing must have a clear understanding of the safety benefits of using the CSTD. In addition, consider ease of disposal of all components; the environmental services department should understand the disposal requirements, eg, terminal waste sizing and appropriate waste segregation as defined by state and federal agencies.

Integration with Compounding Automation
The advent of compounding automation devices for hazardous drugs introduces a new safety process to hazardous drug handling. The only CSTD that fully integrates with compounding automation is the ChemoClave system, which integrates with the Diana system (both products manufactured by ICU Medical, LLC). Other automation systems that incorporate a manual manipulation step in addition to the automated steps could potentially integrate a CSTD into the process. Note that because the current robots are unable to fully account for manufacturer vial pressure differences, altitude effects, and vaporization pressures of the drugs, a CSTD could complement the safety benefits of robots. 

Costs
The cost of a non-reimbursable system often is a consideration when weighing a CSTD adoption. CSTDs may be likened to lead aprons and personal dosimeters in the radiology department—employee safety systems that are not reimbursable. Had lead aprons and personal dosimeters been in use when Marie Curie was investigating the uses of radiation, these safety tools may have saved her life. Thus, as awareness of the risks associated with handling hazardous drugs increases, the evolution of CSTDs in safety programs should shift from a novelty device to a standard of practice as recommended in the NIOSH Alert and the proposed USP <800> chapter. Be sure to account for costs beyond the actual price of the CSTD, including implementation costs, the cost to compound a one-vial dose versus a multi-vial dose (eg, high-dose methotrexate), costs associated with cleaning a spill/spray when not using a CSTD, and the reduced costs resulting from CSTD efficiencies. 

Gaps with Existing CSTDs 
Contaminated Vials
Multiple publications have demonstrated that hazardous drug residue may reside on the outside of the vial when it is received from the manufacturer. To date, none of the CSTDs available have been able to eliminate this residue. Thus, rigorous processes must be in place to ensure that vials are never handled without appropriate PPE and that vials are properly cleaned prior to initiating the compounding process.

Ampule-Based Drugs
Currently, one of the more hazardous drugs, arsenic trioxide (Trisenox; Celphalon, Inc, subsidiary of Teva Pharmaceutical, Inc) is distributed in ampule form. The removal of the drug from the ampule requires snapping the ampule and filtering the contents with a filter straw/needle with a syringe, ie, an open system. Once the drug is in the syringe the CSTD syringe adapter can be added. None of the existing CSTDs have a formal process for managing ampules from container to final product.

Secured Bag Spike
At the time of publication of this article, none of the systems in the US market prevent unspiking of the bag spike from the IV bag. During compounding, administration, and disposal of CSTD-based systems, there is a risk for the IV bag to become unspiked from the closed system, thus opening the system to the environment.  

Routes of Administration
Intraocular, intrathecal, intravesical (for bladder cancer),  and topical routes of administration may pose a risk due to the need to open the system. Having a clear understanding of how hazardous drugs are being administered within facilities considering CSTDs is an important facet of an effective hazardous drug safety program. Consider locations where hazardous drugs are administered, including surgical suites, physician offices, and remote clinics, as well as who will be prescribing, such as ophthalmologists, radiation oncologists, interventional radiologists, interventional cardiologists, and neonatologists.

CSTD Vendor Profiles 
Each manufacturer has put forth significant effort to improve the safety of health care providers and should be acknowledged for their commitment to safety. The following company profiles provide a longitudinal perspective on the steps taken by the different CSTD manufacturers to protect the safety of health care workers who prepare and administer hazardous drugs. 

Tevadaptor (Teva Medical; Israel), AKA OnGuard 
(Distributed by B. Braun USA; Bethlehem, Pennsylvania, USA) 

Tevadaptor is a closed system for drug reconstitution and administration to be used by pharmacists and other health care professionals to prepare drugs, including cytotoxic drugs, for intravenous infusion or injection. The CSTD was designed and developed by Teva Medical (Teva, Israel) in 2003 to address the needs of health care workers. Following the product’s initial prototype design, a complete manufacturing line, including detailed development processes from molding to sterilization, was established in Teva’s manufacturing plant. The quality assurance, regulatory, and engineering expertise required to produce the device meets ISO, IEC, and FDA standards. 

Numerous studies have been published that discuss the deleterious effects of exposure to hazardous drugs; these effects can be significantly reduced by using a CSTD. The Tevadaptor CSTD, when used as part of a comprehensive hazardous drug safety strategy, minimizes the risk of exposure to hazardous drugs and the risk of needle-stick injuries, thus ensuring safety for all health care workers involved in the medication-use process—pharmacists, technicians, nurses, doctors, and disposal personnel. The CSTD was first used in the US at Fountain Valley Regional Hospital (Fountain Valley, CA), Eisenhower Medical Center (Rancho Mirage, CA), and Community Hospital San Bernardino (San Bernardino, CA).

When evaluating CSTDs to identify which device will best fit the needs of an organization, it is critical to take into account the system’s design. Too often pharmacists and nurses may decide not to use a CSTD because the system is difficult to manipulate. Tevadaptor is designed to be user friendly so pharmacists and nurses will use it with minimal workflow disruption; likewise, it requires minimal staff training time. The CSTD can be used as a stand-alone product or as a complementary device in a complete oncology portfolio. 

PhaSeal (Becton, Dickinson and Company; Franklin Lakes, New Jersey, USA)

In the 1980s, initial reports of occupationally linked cancer within the scientific community lead oncology surgeon and scientist, Bengt Gustavsson from Sahlgrenska University Hospital (Gothenburg, Sweden), to design the first completely sealed drug delivery system to enable transfer of hazardous drugs from pharmacy to patient without leakage or environmental contamination. Dr. Gustavsson worked with engineers to create the PhaSeal System to address two main problems: pressure in vials and open wet connections. The device includes a pressure equalization chamber to equalize pressure in the airtight system and utilizes a double membrane technique to ensure dry, leak-free connections. 

Prototypes of the system were created in early 1990, and from 1993 to 1994 performance testing and efficacy validation took place at the University of Gothenburg in a project sponsored in part by the Swedish Work Environment Authority (the Swedish counterpart to OSHA). Carmel Pharma was later formed around PhaSeal, and the first product was sold in Sweden in November 1994.

Two years later, the PhaSeal system was introduced to experts in the US at the MD Anderson Cancer Center and the University of California, San Francisco; shortly thereafter, Thomas Connor and colleagues published a landmark study qualifying hazardous drug contamination in work areas across the US and in Canada.⁷ Concurrently, a study evaluating the effectiveness of PhaSeal’s containment of hazardous drugs in an oncology clinic demonstrated no detectable levels following one year of CSTD use in the preparation and administration of cytostatic drugs.¹ Investigators at NIOSH and the MD Anderson Cancer Center later conducted a similar study evaluating PhaSeal’s ability to contain contamination in a pharmacy setting where high volumes of ifosfamide and cyclophosphamide are prepared, with confirmatory results.² Since then, PhaSeal has been tested in over 30 independent, peer-reviewed studies. 

Carmel Pharma was acquired in July 2011 by BD Medical Surgical Systems, and in September 2012 and February 2013 the PhaSeal System reached two additional milestones by becoming the first CSTD cleared for prevention of microbial ingress and the first cleared under the FDA’s newly created ONB code for the reconstitution and transfer of antineoplastic and other hazardous drugs in health care settings. 

Texium, SmartSite, Vialshield (CareFusion, San Diego, California, USA) 

CareFusion’s chemotherapy safety product line was introduced in December 2013. The chemotherapy safety system includes Texium, a needle-free closed male Luer that connects to SmartSite needle-free connectors to form a closed system (first used in the US at Memorial Hermann Hospital in Houston, Texas). Upon disconnect, the system is drip-free and leak-free to help reduce surface contamination and prevent leaks. Fluid can flow through the Texium connector only when connected to a SmartSite connector. The passive safety system technology of the Texium Luer automatically closes and locks upon disconnection from the SmartSite needle-free connector, helping prevent inadvertent IV set or syringe leaking. Other recent innovations include a full line of SmartSite vial adapters, including the SmartSite VialShield (first used in the US at the Greenville Hospital System, South Carolina), and an FDA-cleared, needle-free CSTD that achieves a closed system without the need for additional parts or pieces when used in conjunction with Alaris IV sets. 

To address nursing’s safety concerns, CareFusion created a line of pre-assembled Texium IV sets that provide automated protection for the administration of hazardous drugs in the patient care areas. The product line also includes a comprehensive line of Texium syringes with the connector permanently affixed to the end of the syringe through a patented process to improve workflow and prevent accidental detachment that could lead to leakage. 

Hospitals that use Alaris IV sets in conjunction with the Alaris line of infusion pumps are already using a portion of the chemotherapy safety system, which creates cost efficiencies, as hospitals that already use the Alaris System need only purchase the SmartSite VialShield and Texium components to create a closed system throughout the continuum of care, from pharmacy to nursing. However, a hospital can use the chemotherapy safety system even if it does not currently utilize Alaris smart pumps.

The new system helps protect health care personnel and patients from being exposed to hazardous drug vapor, spill/spray, and surface contamination during drug reconstitution, transport, and administration. 

Equashield (Equashield; Israel) 

Equashield was conceived when PlastMed, an original equipment manufacturer that makes medical equipment, including fluid transfer devices, sought to develop its own CSTD brand. In 2004, awareness of the potential health risks of hazardous drug exposure increased in the pharmacy community when NIOSH released its alert on preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings.⁵ Equashield founders conducted a market analysis and discovered a niche opportunity within the drug transfer device market, specifically for the safe handling of hazardous drugs. A few years later, with a growing awareness of the need for CSTDs and a perceived gap in the CSTD space, Equashield was officially founded in 2010. 

Development considerations for the new CSTD were driven by user needs. The following elements were included in the design: (1) use of the syringe barrel to store sterile or contaminated air; (2) easy-to-use connectors to prevent needle sticks and ensure dry connections; (3) use of a metal rod as the syringe plunger to prevent plunger contamination; and (4) a fully encapsulated system so that the plunger cannot be removed, thereby preventing major spills. The CSTD was introduced to hospitals and key opinion leaders in closed-door meetings, and due to the positive feedback received, several sites became beta-testing locations for the device, including the Cleveland Clinic. 

The initial device was designed for pharmacy use during drug preparation; however, after the system had been in use at the Cleveland Clinic it became clear that the needs of nurses should be addressed as well. Thus, the design team designed connectors for infusion tubing so that nurses administering hazardous drugs would be protected from exposure along with pharmacists. In 2014, Equashield introduced its second-generation device, EQUASHIELD II, which is easy to use and reduces the time required to handle hazardous drugs safely. In addition, the new CSTD ensures that even when the device is not used properly, it still provides the same high level of protection. Both generations of the device have received ONB product clearance under the FDA’s 510(k) process. 

ChemoClave, ChemoLock, Diana (ICU Medical, San Clemente, California, USA)

ICU Medical’s history is rooted in providing clinicians with effective solutions for handling IV medications safely. In 1984, ICU Medical founder and practicing internist Dr. George “Doc” Lopez lost a patient when an IV line accidentally disconnected. To prevent such a tragedy from happening again, Doc invented a locking IV device called ClickLock. 

ICU Medical’s entrance into the oncology drug handling market also was the product of tragedy and opportunity. In 2006, Doc’s wife, pediatrician Diana Kostyra Lopez, passed away after a long battle with cancer. During her chemotherapy, Diana heard her nurses complain of a metallic taste in their mouths and discuss potential health hazards from exposure to chemotherapy drugs, so she asked Doc to develop a solution that would help keep patients and clinicians safe from hazardous drug exposure. The result is the ICU Medical line of needle-free oncology solutions, comprising the Clave family of needle-free IV connectors and the ChemoClave and ChemoLock needle-free closed systems for the safe handling of hazardous drugs.

The first product created to honor Doc’s promise to his wife was the ChemoClave system, which was built on the same passive, self-sealing safety design features as ICU Medical’s needle-free IV connectors. The system is designed to help clinicians minimize exposure to hazardous drugs at every stage of the safe handling process. The rapid adoption of ChemoClave led ICU Medical engineers to see an opportunity for additional safe handling technology in the pharmacy. The Diana hazardous drug compounding system, launched in late 2012, is a user-controlled, automated compounding system that uses many ChemoClave closed-system components to help clinicians minimize exposure to hazardous drugs and improve preparation traceability while maintaining drug sterility and minimizing physical stress to pharmacists and technicians.

In 2013, ICU Medical launched the ChemoLock needle-free CSTD, a single-motion, click-to-lock device that reduces the potential for insecure or unsafe connections that may jeopardize safety. ChemoLock also is the first needle-free CSTD that has been FDA 510(k)-cleared for both pharmacy compounding (ONB) and patient administration (FPA) applications. 

Conclusion
Occupational exposure to hazardous drugs can occur through unintentional ingestion, inhalation, accidental injection, skin contact, or environmental contamination with hazardous material. Exposure can cause numerous acute conditions (eg, skin rashes, dizziness, nausea) and chronic effects (eg, infertility, miscarriage, birth defects, leukemia or cancers) on human health. Therefore, preventing the serious effects of exposure to hazardous drugs by using CSTDs should be a core feature of every hospital’s hazardous drug management strategy. 

Increased CSTD use signals a new age of hazardous drug safety at the most critical points of the medication use process. Proposed USP chapter <800> highlights the importance of CSTDs by recommending their use during compounding and mandating their use during administration. Regardless of regulations, pharmacy and nursing leaders must commit to a new era of safe hazardous drug handling, as it is incumbent upon us to protect our fellow health care workers. 

The tools are available for organizations to protect health care workers from the harmful effects of hazardous drug exposure. The time is now—for pharmacy and the entire health system—to make a fresh commitment to safe hazardous drug handling.

Firouzan “Fred” Massoomi, PharmD, FASHP, received his doctorate from the University of Kansas School of Pharmacy and is the pharmacy operations coordinator at the Nebraska Methodist Hospital in Omaha. He currently serves on the Nebraska Pharmacists Association Board of Directors. 

References 

1. Sessink PJM, Rolf ME, Ryden NS. Evaluation of the PhaSeal^® hazardous drug containment system. Hosp Pharm. 1999;34:1311-1317.
2. Connor TH, Anderson RW, Sessink PJ, et al. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an IV admixture area. Am J Health-Syst Pharm. 2002;59(1):68-72.
3. Spivey SM, Connor TH. Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV preparation with a closed system. Hosp Pharm. 2003;38(2):135-139.
4. Wick C, Slawson MH, Jorgenson JA, Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003;60(22): 2314-2320.
5. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf Accessed November 17, 2014.
6. US Pharmacopeial Convention. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. http://www.usp.org/usp-nf/notices/compounding-notice. Accessed October 5, 2014.
7. Connor TH, Anderson RW, Sessink PJ, et al. Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. Am J Health-Syst Pharm. 1999;56(14):1427-1432.

Note: Issues/incidents with medical devices can be reported to the FDA’s MedWatch Web site at https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home. To search for issues/incidents with medical devices, go to the MAUDE (Manufacturer and User Facility Device Experience) Web site at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm.)

Suggested Reading List of Seminal CSTD Studies and Reviews 

• Clark BA, Sessink PJ. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract. 2013;19(2):99-104.
• Connor TH, Anderson RW, Sessink PJ, et al. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health-Syst Pharm. 2002;59(1):68-72.
• De Ausen L, DeFreitas EF, Littleton L, et al. Leakage from closed-system transfer devices as detected by a radioactive tracer. Am J Health-Syst Pharm. 2013;70(7):619-623.
• Greemlad M. A new drug handling device for preventing hazardous drug exposure. Eur J Hosp Pharm Pract. 2010;16(5):46-47.
• Harrison BR, Peters BG, Bing MR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health-Syst Pharm. 2006;63(18):1736-1744.
• Massoomi F. CSTDs as a cost of doing business. Pharm Purch Prod. 2012;9(11):10-16.
• McMichael DM, Jefferson DM, Carey ET, et al. Utility of the PhaSeal closed system drug transfer device. Am J Pharm Benefits. 2011;3(1):9-16.
• Nygren O, Olofsson E, Johansson L. Spill and leakage using a drug preparation system based on double-filter technology. Ann Occup Hyg. 2008;52(2):95–98.
• Power LA. Closed-system transfer devices for safe handling of injectable hazardous drugs. Pharm Pract News. 2013;1-16.
• Sessink PJM, Rolf ME, Ryden NS. Evaluation of the PhaSeal hazardous drug containment system. Hosp Pharm. 1999;34(11):1311-1317.
• Sessink PJ, Connor TH, Jorgenson JA, et al. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract. 2011;17(1):39-48.
• Smith ST, Szlaczky MC. Syringe plunger contamination by hazardous drugs: a comparative study. J Oncol Pharm Pract. 2014;20(5):381-385.
• Spivey S, Connor T. Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV preparation with a closed system. Hosp Pharm. 2003;38(2):135-139.
• Wick C, Slawson MH, Jorgenson JA, et al. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003;60(22):2314-2320.
• Zock MD, Soefje S, Rickabaugh K. Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activities using two closed-system products. J Oncol Pharm Pract. 2011;17(1):49-54.