Understanding Closed-System Transfer Devices: Why They Are Important and How to Select an Appropriate System

Specialty Pharmacy Times, May/June 2016, Volume 7, Issue 3

CSTDs can help protect health care workers, including pharmacists and nurses, from hazardous chemotherapy drugs.

CLOSED-SYSTEM TRANSFER DEVICES, OR CSTDS, are defined by the National Institute for Occupational Safety and Health (NIOSH) as, “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.”

These systems are important in protecting health care professionals from exposure to potentially cytotoxic and teratogenic medications both during product preparation and administration.1

The Importance of CSTDs in Protecting Health Care Professionals

CSTDs help protect health care professionals from hazardous drugs, including pharmacists preparing medications and nurses administering medication. It has been estimated that 8 million health care professionals are exposed to hazardous drugs each year, increasing the risk of chromosomal abnormalities, teratogenicity, and cancer. More than 100 studies substantiate the increased risk, and more than 50 studies have documented harm to health care workers as a result of exposure.2-4

In a 1999 study published in the Journal of Occupational and Environmental Medicine, Valanis and colleagues analyzed pregnancy outcomes in nearly 3000 nurses, pharmacists, and pharmacy technicians and compared those outcomes with those in more than 4000 women who were not health care workers. In health care workers, spontaneous abortion or stillbirth was 40% more likely (OR 1.4; 95% CI, 1.2-1.7) to occur in individuals who reported handling hazardous drugs.5

In 2010, McDiarmid and colleagues published a study in the Journal of Occupational and Environmental Medicine identifying a higher rate of chromosome 5 and 7 abnormalities among health care workers frequently handling antineoplastic medications than in health care workers who handled such medications less frequently.

Researchers collected blood samples from more than 100 health care workers and analyzed the likelihood of chromosomal abnormalities related to the frequency of hazardous drug handling in each individual. Findings indicated significantly higher rates of structural chromosomal abnormalities in a high-exposure subset of health care workers than in a low-exposure group (0.18/person vs 0.02/person, respectively; P = .04).

Significant outcomes included a 24% greater risk of chromosome 5 abnormalities (P = .01) and a 20% greater risk of chromosome 5 or 7 abnormalities (P = .01) in high-exposure individuals.6 These studies are not merely an academic exercise. Exposure to hazardous drugs has real-world consequences.

Before she died of pancreatic cancer, pharmacist and hazardous drug compounding advocate Sue Crump reported, “One of my friends after another was coming down with either some very rare, exotic, bizarre disease; brain tumors; sarcoidosis; arrhythmias; or cancer.”

When Sue developed pancreatic cancer at the age of 55 after a 23-year career in oncology pharmacy practice, she turned to the media and drew attention to the issue of inadequate protective controls in hazardous drug compounding.7

Sue’s case did not occur in isolation. Pharmacist Bruce Harrison, veterinarian Brett Cordes, and nurse Sally Giles all eventually developed cancer or precancerous conditions in their fourth or fifth decade of life after being exposed to the occupational risk of hazardous drug handling.

Sadly, Bruce Harrison, who had a key role in developing hazardous drug handling guidelines, died at the age of 59. Sally Giles died of bile duct cancer in 1992. Brett Cordes has since recovered from cancer, but has left private practice to advocate for improved compounding safety standards.7

Use of CSTDs can help protect health care workers from exposure to hazardous medications. However, when considering a CSTD, it is important to understand that this set of products have very different design characteristics and, with regard to protective efficacy, some products have been studied extensively with high-quality trials—and others have not.

The Design of CSTD

Over the course of nearly 3 decades, a variety of CSTDs have been approved for use in the United States, starting with the 1998 approval of the BD Phaseal CSTD. For 7 years, Phaseal was the only available CSTD until the approval of Spiros in 2005, followed by Texium and Tevadaptor in 2006, ChemoClave in 2008, Equashield in 2009, ChemoLock and Vialshield in 2012, and the latest product, Equashield II, which was approved in 2014.9

All of these products have 3 characteristics in common: 1) they are supplemental engineering controls designed to protect health care professionals from hazardous medications, 2) they are designed to equalize the pressure gradient between the syringe and container from which liquid is drawn or expelled, and 3) they are used both in compounding and administration of medication.9

However, CSTDs are a diverse set of products that differ in ease of use, design characteristics, and the quality of data supporting each product’s performance.

To understand the basic design characteristics of a given CSTD, it is important to ask 3 questions9:

  • Does the CSTD use a chamber or an air-cleansing system to equalize pressure differences between the syringe and medication container?
  • What type of membrane is present at the junction between the syringe and the medication container: a double-membrane connector or a different type of connector?
  • Does the CSTD use a metal needle or a needle-free connection system?

With respect to these characteristics, to equalize the pressure gradient between the syringe and the medication container (eg, a vial), some CSTDs rely on an air-cleansing filter, whereas others rely on a closed chamber. Importantly, systems that rely on air-cleansing filters cannot be evaluated for protective efficacy using the NIOSH Vapor Containment Performance Protocol.

This protocol, which relies on detection of very low levels of isopropyl alcohol within a closed chamber, is the newest and most reliable standard for evaluating CSTD performance (described in full later in this article).9,10

Another key difference is the use of a needle-free connector versus a standard metal needle. This is an important consideration because needle-free connectors are potentially easier to work with, but are more prone to contamination than metal needles, and may require purchase of specialized equipment that works with the CSTD. Conversely, CSTDs that rely on a metal needle may cause needle sticks, but are less prone to contamination and can be used with existing equipment unlike needle-free connectors.9

A third considerations is the interface between the vial and the needle. Some systems use a double-membrane junction between the syringe and the medication vial or container to help isolate medications, whereas others do not use this technology, and rely on other vial/device interfaces. A double-membrane containment system is an added layer of protection is used by both the newest CSTD, Equashield II, and the CSTD with the longest track record, PhaSeal (see Table 1).9

Protective Efficacy It is important to choose a system that has robust evidence of efficacy in protecting health care workers. Specific evidence includes the following:

  • More than 25 published studies support the performance and efficacy of the BD PhaSeal System in protecting health care workers from hazardous drugs (see www.bd.com/pharmacy/phaseal/evidence/studies.asp).
  • In a 2011 study published in the Journal of Oncology Pharmacy Practice, Sessink et al reported levels of surface contamination of antineoplastic drugs in 22 US hospitals before and several months after adoption of the BD PhaSeal CSTD system. However, the levels of surface contamination found after for all 3 antineoplastic drugs sampled were significantly lower: cyclophosphamide (95% reduction; P <.0001), ifosfamide (90% reduction; P <.001), and 5-fluorouracil (65% reduction; P <.01).11
  • In a 2003 study published in the American Journal of Health Systems Pharmacy, Wick and colleagues determined that the BD PhaSeal system led to real-world reductions in personnel exposure. Before and 6 months after implementation of the BD PhaSeal CSTD in a hospital pharmacy, all personnel were evaluated using 24-hour urine samples. Of 8 employees, 6 showed evidence of exposure to cyclophosphamide and 2 showed evidence of ifosfamide exposure prior to use of the BD PhaSeal System. After implementation, none of the 8 employees had evidence of cyclophosphamide or ifosfamide in their urine samples.12
  • In a 2013 study published in the Journal of Oncology Pharmacy Practice, Clark and colleagues reported the efficacy of the EquaShield CSTD on reducing surface contamination at a single cancer center before and after the system’s adoption. Researchers used a kit to collect samples from 5 areas of the pharmacy, 5 areas of the infusion suite, and 2 areas in offices. Whereas approximately half of the samples showed contamination before, no contamination with cyclophosphamide or 5-fluorouracil was identified in the final sample collection.13

Although reductions in environmental contamination are the most difficult standard to meet with regard to CSTD efficacy, other efficacy measures have been developed. These include testing with titanium vapor, smoke, and sulfur hexafluoride.

By analyzing whether or not any of these vapors or gasses escape from a CSTD can help validate the protective efficacy of a given system. Other tests using dyes, such as fluorescein, have also been performed.8

Two very simple, but less scientific tests, may be performed without special equipment. In one such test, simply transferring coffee from a vial to a CSTD may help qualitatively validate efficacy. Due to the distinct smell of coffee, any coffee aroma present during or shortly after transfer may indicate leakage.

In another qualitative test, transfer of lemon juice from a vial to a CSTD while holding a strip of litmus paper held near the junction between the vial and syringe can help validate the protective efficacy of a CSTD. In the lemon juice test, any color change of the litmus paper may indicate an imperfect seal and inadequate protective efficacy.8

In contrast with these earlier tests and unscientific informal demonstrations, NIOSH recently developed a Vapor Containment Performance Protocol as the standard for evaluation of CSTD protective efficacy.

This protocol, which was approved in early 2016, relies on an easily obtained standardized compound: 70% isopropyl alcohol (IPA). This tracer compound generates vapor at room temperature, and vapors can be reliably detected at very low concentrations using a gas analyzer.8,10

In performing the protocol-defined test, a tester transfers IPA from a vial to a CSTD within a sealed chamber (the Secador Techni-dome 360 Large Vacuum Desiccator). Using a gas analyzer (Miran SapphIRe) to analyze any change in the atmosphere of the sealed chamber, it is possible to confirm that an amount of IPA <1 part per million (ppm) has escaped from the CSTD. This 1-ppm lower limit of detection—equivalent to 1 teaspoon of water in a 5000-liter tank—confirms the protective efficacy of a CSTD to a very high standard.8,10

CSTDs and USP <800> USP <800> are legally enforceable regulations that were approved in early 2016. These regulations are intended to protect health care workers from hazardous medications through identification and separation of hazardous drugs from other medications during transport and storage and 2) preparation and administration of hazardous drugs under protective conditions that reduce the risk of hazardous drug exposure in health care workers.14

With respect to CSTDs, USP <800> changes 3 important policies14:

  • USP <800> updates a previous policy in USP <797> that allowed preparation of some hazardous drugs within a primary engineering control hood (eg, a class II or better biological safety cabinet) that is also used for preparation of nonhazardous medications, provided the cabinet is cleaned after preparation of the hazardous drug; USP <800> eliminates this practice.
  • Under USP <797>, a CSTD could be used within a primary engineering control hood located in a positive-pressure environment; USP <800> disallows this practice, and requires use of CSTDs only within a primary engineering control hood located in a negative-pressure environment.
  • For administration of chemotherapeutic medications, nurses are required to use a CSTD, provided the CSTD materials are compatible with the medications being administered (eg, CSTDs cannot be used with bendamustine because bendamustine will chemically destroy the materials that make up the CSTD).

Once fully implemented and enforced, these changes will have important effects on pharmacy departments across the United States. For example, all nursing departments will have access to CSTDs, but pharmacies will not be absolutely required to use these protective systems.

As of 2014, a survey of pharmacy departments indicated that 35% used CSTDs, compared with 32% of nursing departments. With USP <800>, these differences are likely to reverse, with more nursing departments than pharmacy departments having access to the technology.

By engaging with nursing stakeholders, pharmacists can discuss the properties of CSTD devices and negotiate shared access to CSTD systems that are suitable and convenient for both compounding and administration of hazardous drugs.9,15

However, before engaging with nursing stakeholders, it is important for all pharmacists to read USP <800> and to start preparing. Pharmacists and pharmacy departments can start by making a list of all hazardous drugs present in their institution, as defined by NIOSH in the NIOSH list of antineoplastic and other hazardous drugs (some medications and considerations for implementation of USP <800> are listed in Table 2).

The NIOSH list was last updated in 2014, and will be updated in 2016. For the 2016 update, several medications are being considered for inclusion in the hazardous drug list (see Table 3). As of this publication, NIOSH is still accepting public comments on these proposed additions.9,16

Conclusions

CSTDs have an important role in protecting health care professionals from the risks of long-term low-level exposure to hazardous drugs both during preparation in the pharmacy and during administration at the bedside by nurses.

By understanding some of the important properties of CSTDs, recognizing the evidence supporting use of specific CSTD systems, understanding the key design characteristics of specific CSTD systems, and collaborating with nursing colleagues, pharmacists can better prepare for USP <800>, protect themselves and their colleagues from the risks of hazardous drug exposure, and foster a culture of safety and caring—both for patients and the health care professionals who care for them. SPT

References

  • NIOSH. Preventing occupational exposures to antineoplastic drugs. CDC website. www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf. Accessed May 2016.
  • Gabay M. USP <800>: handling hazardous drugs. Hosp Pharm. 2014;49(9):811-812. doi: 10.1310/hpj4909-811.Massoomi F. USP <800> and the expected impact on health systems. Pharmacy Advisor website. www.pharmacyadvisor.com/resources/uploads/webinar_handouts/55/usp_800_and_the_expected_impact_on_health_systems.pdf. Published July 2014. Accessed May 2016.
  • Mixon B. USP <800>: what you need to know. http://c.ymcdn.com/sites/www.pssny.org/resource/resmgr/USP_800_presentaton_to_PSSNY.pdf. Accessed May 2016.
  • Centers for Disease Control and Prevention. Occupational exposure to antineoplastic agents and other hazardous drugs. CDC website. www.cdc.gov/niosh/topics/antineoplastic/pubs.html. Accessed May 2016.
  • Valanis B, Vollmer WM, Steele P. Occupational exposure to antineoplastic agents: self-reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med. 1999;41(8):632-638.
  • McDiarmid MA, Oliver MS, Roth TS, Rogers B, Escalante C. Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med. 2010;52(10):1028-1034. doi: 10.1097/JOM.0b013e3181f73ae6.
  • Page MR. Protecting health care workers from chemotherapeutic medication. Specialty Pharmacy Times website. www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2015/june-2015/protecting-health-care-workers-from-chemotherapeutic-medication. Published June 9, 2015. Accessed May 2016.
  • Page MR. Closed-system transfer devices: design characteristics and evolving performance standards. Specialty Pharmacy Times website. www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2015/december-2015/closed-system-transfer-devices-design-characteristics-and-evolving-performance-standards. Published December 10, 2015. Accessed May 2016.
  • Page MR. Selection of closed-system transfer devices: tips for engaging nursing and pharmacy stakeholders in purchasing decisions. Pharmacy Times website. www.pharmacytimes.com/publications/health-system-edition/2016/march2016/selection-of-closed-system-transfer-devices-tips-for-engaging-nursing-and-pharmacy-stakeholders-in-purchasing-decisions. Published March 24, 2015. Accessed May 2016.
  • Hirst DVL, Mead KR, Powers L, et al. A vapor containment performance protocol for closed system transfer devices used during pharmacy compounding and administration of hazardous drugs. CDC website. www.cdc.gov/niosh/docket/review/docket288/pdfs/a-vapor-containment-performance-protocol-for-closed-system-transfer-devices.pdf. Accessed May 2016.
  • Sessink PJ, Connor TH, Jorgenson JA, Tyler TG. 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. doi: 10.1177/1078155210361431.
  • 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):2314-2120.
  • 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. doi: 10.1177/1078155212468367.
  • Page MR. USP <800>: key changes and additions to USP <797>. Specialty Pharmacy Times website. www.specialtypharmacytimes.com/publications/specialty-pharmacy-times/2016/february-2016/usp-800-key-changes-and-additions-to-usp-797. Published February 9, 2016. Accessed May 2016.
  • Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2011. Am J Health Syst Pharm. 2012;69(9):768-785. doi: 10.2146/ajhp110735.
  • Centers for Disease Control and Prevention. Proposed additions to the NIOSH 2016 hazardous drugs list. www.cdc.gov/niosh/docket/review/docket233a/pdfs/proposed-additions-to-the-niosh-2016-hazardous-drugs-list-05-11-2015.pdf. Accessed May 2016.