HAZARDOUS DRUG EXPOSURES IN HEALTHCARE
Closed System Drug-Transfer Device (CSTD) Research
NIOSH defines a Closed System Drug-Transfer Device (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” [NIOSH 2004]. Currently, CSTDs generally follow one of two design concepts, using either a physical barrier or an air-cleaning technology to prevent the escape of hazardous drugs into the work environment. When appropriately designed and used, CSTDs offer enhanced protection against potentially hazardous exposures to healthcare workers during the compounding and administration of hazardous drugs.
NIOSH recommends healthcare workers use a CSTD throughout the hazardous drug-handling chain, from pharmaceutical compounding to patient dose administration [NIOSH 2004]. While all CSTDs may not be equally protective, research shows that CSTD use can reduce hazardous drug contamination [Vyas 2013]. CSTDs should not be the only means of worker protection. They should be used as part of a hazardous drug safety program and used in conjunction with other engineering controls [NIOSH 2004].
CSTD Performance Standards
As CSTD designs and available models changed, NIOSH and its industry partners realized the need for an independent testing method for CSTD performance.
While CSTD performance standards are available that apply to sterile practice and patient protection, no CSTD performance standards are available for drug containment [Douglass et al. 2012]. To address this gap, NIOSH researchers are developing a test protocol that evaluates a CSTD’s containment of hazardous drugs.
NIOSH Research on CSTD Test Protocols
The following is information on NIOSH CSTD research activities and includes links to early draft protocols, other associated documents, and public comments. Also provided is an update on the research status of the most-recent NIOSH draft CSTD test protocol. This is a unified test protocol for both air-cleaning and barrier type CSTDs. Check back for more on this continuing NIOSH research project and other relevant CSTD information.
NIOSH’s First Draft CSTD-Test Protocol
NIOSH published a public comment draft protocol entitled, “A Vapor Containment Performance Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs.” The draft protocol tested the containment performance of the physical-barrier type of closed system transfer devices (CSTDs), but it was not designed to test air-cleaning type CSTDs.
NIOSH scientists developed this protocol with input from registered pharmacists experienced with CSTD use. The pharmacists performed the protocol’s prescribed compounding and administration tasks for five commercially available CSTDs with 70% isopropyl alcohol (IPA) as the challenge agent. They also tested a negative control condition without a CSTD. The tests were conducted in an environmental test chamber, and a gas analyzer was used to detect vapor concentrations of escaped IPA during the tasks.
This protocol had several potential applications including that it could be used by:
- manufacturers to evaluate prototype CSTDs,
- consumers to compare CSTD products, or
- jurisdictions who wished to adopt the protocol for a CSTD performance certification procedure.
The protocol was posted for public comment at www.regulations.govExternal (CDC-2015-0075) and NIOSH Docket Number 288. The original draft plus submitted public comments can be found at https://www.cdc.gov/niosh/docket/archive/docket288.html.
NIOSH’s Air-Cleaning CSTD Protocol
After receiving public comments following the original draft protocol, NIOSH sought stakeholder input to develop a performance test protocol for CSTDs that use air-cleaning technology. The original request for comments can be found in this document: Federal Register Notice 2016-00827Cdc-pdf.
NIOSH’s Unified CSTD Test Protocol
As the public submitted comments on the development of an air-cleaning type CSTD test protocol, NIOSH began investigating a unified CSTD test protocol which could be used to evaluate both air-cleaning and barrier-type CSTDs. NIOSH published an early draft of a unified test protocol, “A Performance Test Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs,” in September 2016 and requested public comment.
NIOSH also held a public meeting at NIOSH facilities in Cincinnati, Ohio, on November 7, 2016 to discuss the draft unified protocol. The draft unified protocol, meeting announcement, and submitted public comments can be found at https://www.cdc.gov/niosh/docket/archive/docket288a.html.
Potential Challenge Agents
As of September 2018, substantial progress has been made on the unified protocol. A key challenge in developing the unified protocol has been identifying challenge agent(s) with physical properties similar to hazardous drugs, in particular, their volatility. As NIOSH researchers identified potential challenge agents, they sought feedback from CSTD manufacturers to minimize the potential for material incompatibilities between the challenge agent and the CSTD components.
Methods to Detect Challenge Agents
Along with challenge agent identification, an analytical method(s) is needed to detect the challenge agent(s) at low concentrations and in a manner compatible with the CSTD test protocol’s procedural steps. At the public meeting on November 7, 2016, two alternative detection methods were proposed: thermal desorption tubes with gas chromatography and mass spectrometry analysis (TD-GC-MS); and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS). After considering the submitted public comments that indicated the desire for real time monitoring, and conducting additional research, NIOSH anticipates that the analytical method to detect chemical leakage will be SIFT-MS. This technique is expected to provide real-time detection capabilities whereas the sorbent media sampling techniques would require considerable time between sample collection and analysis.
Multicomponent Test Solution
NIOSH has developed a multicomponent test solution to detect leaks of the challenge agent(s). If a leak is detected, this solution may help diagnose whether the leak is a liquid leak or a vapor leak. The addition of a fluorescent marker to the test solution may also facilitate identifying leak locations, if they occur. NIOSH is working to optimize the multicomponent test solution and analytical method and incorporate these features into the unified CSTD test protocol.
Q1: In what situations can the initial Draft CSTD protocol be used?
Response: While the initial draft protocol (CDC–2015–0075, Docket Number NIOSH–288, September 8, 2015) is not an appropriate evaluation tool for air-cleaning CSTDs, it is a robust test protocol applicable to barrier-type CSTDs. There are a variety of situations where the initial draft protocol is still an appropriate evaluation tool. Some examples include its use in support of research and development activities by a barrier-type CSTD manufacturer, as an evaluation tool for educational environments, or as a worker-proficiency evaluation tool within a facility that has chosen to use a barrier-type CSTD. It is important to note that results derived from the initial draft protocol should not supersede any future performance results obtained under a final NIOSH-developed CSTD test protocol.
Q2: Recently, I have seen claims about CSTDs that have already “passed” the Unified CSTD test protocol applicable to both barrier and air-cleaning types of CSTDs. Is that possible?
Response: NIOSH is aware of articles and advertisements reporting CSTD performance results that state they are based on NIOSH’s draft Unified test protocol (CDC-2016-0090, Docket Number NIOSH–288-A, September 15, 2016). However, a Unified test protocol has not been finalized; it is incomplete and many key components are being addressed, such as selection of evaluation surrogate(s), the associated surrogate concentrations, sampling and analytical methods, and even the test chamber design. In addition, NIOSH does not anticipate publishing pass/fail criteria as part of the final protocol. Such criteria will depend upon the protocol’s specific application. Just like the first protocol however, NIOSH may incorporate guidance that assists protocol users in determining their own pass/fail performance metrics.
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