How Closed-System Devices Protect Healthcare Workers from Dangerous Drugs
A silent threat lurks in hospitals where life-saving treatments are prepared
When we picture healthcare workers, we often imagine them facing immediate dangers like infectious diseases or needlestick injuries. However, a more insidious hazard hides in the very medications they handle daily—hazardous drugs that can cause cancer, fertility problems, and other serious health issues with long-term exposure.
For nurses, pharmacists, and pharmacy technicians who prepare and administer powerful infusional hazardous drugs—particularly cancer treatments—low-level daily exposure poses a significant occupational risk. This article explores how the healthcare community is fighting back against this invisible threat through safe handling protocols and innovative closed-system drug-transfer devices (CSTDs).
The National Institute for Occupational Safety and Health (NIOSH) defines hazardous drugs as those exhibiting specific dangerous characteristics in humans or animals. A drug can be classified as hazardous if it demonstrates just one of the following properties2 :
Potential to cause cancer
Potential to cause birth defects or developmental toxicity
Impairment to reproductive capacity
Toxic effects on organs at low doses
While this category includes many chemotherapy agents, it also encompasses other drugs that meet these criteria. The NIOSH List of Hazardous Drugs serves as the primary reference for healthcare facilities when determining which medications require special handling.
Before exploring high-tech solutions, it's crucial to understand the foundation of protection: safe handling practices. These include2 9 :
Such as biological safety cabinets (ventilated enclosures) and compounding aseptic containment isolators
Including gloves, gowns, and respiratory protection
Like specific procedures for handling spills and waste
Including staff training and medical surveillance
These measures represent the minimum standard for protecting healthcare workers when handling hazardous drugs. But are they enough?
To provide an additional layer of protection, closed-system drug-transfer devices (CSTDs) were developed. NIOSH defines a CSTD as "a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of the hazardous drug or vapor concentrations outside the system"1 .
Think of CSTDs as sophisticated, sealed pathways that allow healthcare workers to withdraw drugs from vials and inject them into IV bags without ever being exposed to the contents. These systems generally follow one of two design concepts1 :
That use mechanical barriers to prevent contamination
That captures vapors and particles
Major organizations including NIOSH, the United States Pharmacopeia (USP), and professional oncology societies recommend or require CSTDs as part of a comprehensive hazardous drug safety program1 .
Given the significant investment CSTDs require, researchers have sought to determine their true effectiveness. In 2018, the Cochrane Collaboration published a comprehensive systematic review that analyzed all available evidence comparing CSTDs plus safe handling versus safe handling alone3 5 .
The research team employed rigorous systematic review methods:
They searched multiple scientific databases including CENTRAL, MEDLINE, Embase, and others up to October 2017
Included were comparative studies of any design that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs
They calculated risk ratios and mean differences with confidence intervals, assessing evidence quality using GRADE methodology
The review incorporated 24 observational studies conducted across 359 hospitals. Notably, no randomized controlled trials were found, highlighting a significant gap in the research landscape. Most studies focused on pharmacists and pharmacy technicians, and the most commonly evaluated system was the PhaSeal CSTD5 .
The results presented neither a clear victory nor defeat for CSTDs:
| Outcome Measure | Findings | Certainty of Evidence |
|---|---|---|
| Urine tests for drug exposure | No evidence of difference between CSTD and control groups | Very low |
| Surface contamination (proportion) | Reduction for only 1 of 24 drug/area combinations (5-fluorouracil) | Very low |
| Surface contamination (amount) | Reduction for only 2 of 15 drug/area combinations (cyclophosphamide in pharmacy areas) | Very low |
| Health outcomes | No studies reported skin rashes, fertility issues, or cancer outcomes | No evidence |
| Cost savings | Inconsistent results across studies | Very low |
The authors concluded: "There is currently no evidence to support or refute the routine use of closed-system drug-transfer devices in addition to safe handling of infusional hazardous drugs"5 .
This doesn't mean CSTDs are ineffective—rather, that the existing evidence is too limited and of insufficient quality to draw firm conclusions.
Despite the uncertain evidence base, innovation in CSTD technology continues to advance. Recent research has focused on improving device design and functionality.
Chinese researchers have developed a novel CSTD with an automatic pressure-relief structure designed to reduce hand strain during drug transfer while maintaining a tight seal against leaks7 . Their 2025 study compared their new device against conventional syringes using several drugs, including the hazardous drug cyclophosphamide.
| Drug Tested | Syringe Leakage | CSTD(JLY) Leakage | Significance |
|---|---|---|---|
| Fluorescein sodium | 1.14% | 0.07% | P < 0.01 |
| Lansoprazole | 0.91% | 0.09% | P < 0.01 |
| Nimodipine | 0.86% | 0.08% | P < 0.01 |
| Tropisetron | 0.95% | 0.07% | P < 0.01 |
| Cyclophosphamide | 0.89% | 0.08% | P < 0.01 |
The study demonstrated that the novel CSTD significantly reduced drug leakage compared to conventional syringes, potentially offering better protection for healthcare workers7 .
| Tool Category | Specific Examples | Function |
|---|---|---|
| Primary Engineering Controls | Biological Safety Cabinets (BSCs), Compounding Aseptic Containment Isolators (CACIs) | Provide ventilated enclosure for drug preparation to contain airborne particles |
| Closed-System Drug-Transfer Devices | PhaSeal, EquaShield, Tevadaptor, BD Phaseal, CSTD(JLY) | Mechanically block escape of hazardous drugs during transfer between containers |
| Personal Protective Equipment | Chemo-rated gloves, gowns, respiratory protection, face shields | Create barrier against skin contact, inhalation, and accidental splashes |
| Monitoring Equipment | Surface wipes, gas analyzers, FTIR spectroscopy | Detect and measure environmental contamination |
The journey toward optimal protection for healthcare workers faces several challenges:
The Cochrane review highlighted the urgent need for better-designed studies, suggesting multicentre randomised controlled trials or interrupted time-series studies as potential paths forward5 .
CSTDs represent a significant financial investment for healthcare facilities, with studies showing conflicting results on potential cost savings3 .
Recent reports indicate that some CSTDs may impact drug quality, causing issues such as protein aggregation or particle formation, particularly with biologic drugs.
NIOSH is actively working to develop a unified test protocol to reliably evaluate CSTD performance across different designs1 .
The protection of healthcare workers who handle hazardous drugs remains a complex challenge at the intersection of occupational safety, clinical practice, and technology development. While closed-system drug-transfer devices offer a promising additional layer of defense, they are not a standalone solution.
The current scientific evidence suggests that CSTDs should be viewed as part of a comprehensive safety program that includes proper engineering controls, personal protective equipment, and rigorous safe handling practices—rather than as a replacement for these fundamental protections.
As research continues and technology evolves, the goal remains clear: ensuring that the healthcare workers who dedicate their lives to caring for others aren't forced to sacrifice their own health in the process. The invisible hazard of hazardous drug exposure may be hidden, but the commitment to protecting those on the front lines of medical treatment should remain visible and unwavering.