Q & A with Luci Power, MS, RPhSenior Pharmacy Consultant
Power Enterprises

Pharmacy Purchasing & Products: Given that guidelines exist for handling hazardous drugs, why does compliance continue to be variable?
Luci Power: The degree of awareness of the occupational risks involved with hazardous drug handling is the main problem. While concern over the risks of handling hazardous drugs has been around since the late 1970s, new generations of health care workers are even less aware of the problem now. Some assume we solved the problem years ago, but we never have. Many pharmacy practitioners want hard evidence in the form of casualties directly related to exposure before they will believe there is an issue. Unfortunately, the risks are subtle and progress slowly in the form of reproductive and genetic damage and cancer development. These developments, often many years in the making, are difficult to tie directly to exposure from hazardous drug handling.

Immediate adverse reactions are reported in the literature and surveys of adverse events in health care workers as well as reproductive risks have been published, but there is no database or registry in the United States for reporting such events or for surveying the frequency of their occurrence; so for some, the data is not sufficiently compelling. From my perspective, it is clear that significant insidious data has been around for decades. Today’s cancer treatment drugs are more potent, the doses are much larger, and many drugs considered hazardous have evolved to other therapies such as immunosuppression and antiviral regimens. Traditional hazardous drugs, such as antineoplastic agents, are now used in non-cancer treatments and in non-human treatments. These venues employ workers even less aware of the risks than hospital pharmacy practitioners. Of particular concern are veterinary workers as their work environment makes containment very difficult.

PP&P: What are the primary exposure concerns for pharmacy workers handling hazardous products?
LP: Immediate effects of exposure may include skin and eye irritation if the drug gets on or into the body. Reports of abdominal issues have been published following severe overexposure from a large spill. Nail discoloration, nail sores, and hair loss have all been reported in surveys of health care workers handling chemotherapy. The largest number of reports, however, has been on reproductive risks. While infant malformations have been reported in the literature, the inability to conceive or fetal loss appear as the most frequent issues in health care workers exposed to hazardous drugs. These reports include studies that have shown a potential for infertility in male and female health care workers due to exposure.

As many hazardous drugs have been shown to be carcinogenic in treated patients, it is a reasonable concern that occupational exposure may lead to cancer. Direct studies of exposed workers are few, as finding the numbers is difficult with no registries to pull cases from. We have seen recent attempts by investigative journalists to quantify the issue, and while the numbers are still not high, putting faces to the afflicted makes a powerful impact (See www.invw.org/chemo-main). Recently published in the Journal of Occupational and Environmental Medicine, a NIOSH study of three major health care facilities found surface contamination throughout the facilities, and a section of the study that looked at genetic effects found chromosomal damage consistent with occupational exposure to carcinogens. As the study’s testing protocols provide definitive data there will be more to examine and more to report. How this will affect pharmacy policies and procedures and what we will do to avoid the exposure is still unknown. This data will, however, address the question of direct casualties—a tragic but effective way to raise awareness.

PP&P: Under what circumstances do you recommend the usage of closed-system drug-transfer devices (CSTDs)?
LP: While not a perfect solution, CSTDs have been shown to reduce the amount of drug residue released into the environment during the compounding of hazardous drugs and during administration activities at the point of care. CSTD systems are the only types of containment technology that have addressed exposure during administration; a point where nurses have had no risk-mitigating technology in the past. Nurses have had to rely exclusively on good work practices and techniques to avoid contaminating patient areas, as well as themselves. Drug residue has been found on floors, in trashcans, and on infusion pumps in patient-care areas. This contamination then transfers to other health care workers, such as housekeeping staff, and to others in the area, including patient visitors or companions in outpatient settings.

Supplying CSTDs demonstrates a tangible concern for worker and staff safety. The devices are being provided for compounding and administration, the staff is being trained to use them, and their use is enforced. This sends a positive message of awareness and concern.

Looking at this issue from a supervisor’s viewpoint, I can tell that a CSTD is in use and I can monitor proper use by random observation, whereas simply enforcing good handling technique and/or other work practices requires constant observation and monitoring. In addition, most hazardous drugs are clear and colorless, so spills and drug residue are not immediately apparent. CSTDs are less likely to be affected by rushing or interruptions than good technique. Other challenges include new pharmacy setups per USP Chapter <797> where the actual compounding area and the primary engineering control (PEC) are remotely located. Constant, visual monitoring of individual technique is unlikely in such a scenario.

PP&P: What do you make of the controversy surrounding the accepted terminology for these devices? Is there validity to claims of a true “closed-system” device?
LP: NIOSH developed the generic term “closed-system drug transfer device” for the only device that existed at the time of the 2004 NIOSH Alert on Hazardous Drugs. This is merely a characterization. There has never been a performance standard developed to determine what a CSTD is supposed to do. This has been problematic, as more companies have brought devices to the market and received FDA approval by using the first CSTD as their predicate device. The new devices often differ greatly from the initial one and many have filters or other components that may result in a less effective system. The initial device was studied in the clinical setting in multiple sites and over various periods of time. These studies showed that the CSTD reduced surface contamination when compared to work practices and good technique. To date, no studies have been published that fully examine more than one of the CSTDs in comparable settings. This type of study would not be easy to conduct but it is difficult to evaluate the devices without some objective criteria.

PP&P: What are the key points that pharmacy should use to evaluate the different closed-system drug transfer devices that are available?
LP: As no system is perfect, the evaluation process will be fairly subjective. Fred Massoomi’s article, “Assessing Vial Transfer Devices for Handling Hazardous Drugs," published in Pharmacy Purchasing & Products’ March 2009 issue contains a number of tests to evaluate the various CSTDs without laboratory validation. However, without an established performance standard, these testing methods are subjective. In theory, testing criteria could include ease of training on the product; evaluating incidents of product failure during the testing process; perceived ease of use both in the compounding process and the administration process; compatibility with other parts of the infusion system (eg, pumps, y-site connectors); application of a true needle-free device; and, of course, cost.

PP&P : When budget is an issue, what approach should pharmacy use to ensure approval of CSTD acquisition?
LP: Budget is always an issue in pharmacy, so cost has to be part of the evaluation. I would suggest that the pharmacy department enlist a champion—a pharmacist, oncology nurse, or occupation-medicine practitioner to generate a consensus among all affected individuals, not just pharmacy. Plan a campaign that includes literature back up, regulatory requirements, and the support of influential staff members. As long as CSTDs remain a non-mandated safety process, reimbursement is unlikely. Perhaps the best way to gain budget approval for CSTDs is to focus on other cost reductions that may be achieved through their use. Examine the entire hazardous drug process and see if employing CSTDs could reduce the cost burdens of other elements in the system. For example, there is a lot of discussion about CSTDs being used as “dispensing pins” allowing for larger vials to be used with more draws from that vial as the CSTD acts as a de facto airtight seal. This reduces the overall cost of the vial cap. Also, studies are being done to examine the effectiveness of certain CSTDs in maintaining the sterility of single-dose vials, allowing for an extension of the six-hour use rule in USP <797>. While this is a quality assurance process, and it must be specific to each compounding environment and to individual compounding staff, this can be part of a system where a continuous process is developed to monitor sterile compounding for the department and each staff member. It could be an addition to media-fill testing using the CSTD components.

PP&P: How can pharmacy management ensure continuous proper technique by staff members using CSTDs?
LP: As with all equipment, proper training is required in learning a new technique. There are issues with all CSTD systems that may result in failure if training or operation is compromised. Some CSTDs have spikes that may be /left protruding with poor technique; some are more easily disconnected from the syringe than the vial adapter, creating a leak; some do not equilibrate the air and require drawing ambient air into the syringe before attaching the “closed” syringe attachment; some have more adapters than others, demonstrating greater versatility but also creating more risk.

As a faculty member at the Baxa STAR Center, part of the curriculum I teach involves a demonstration of negative pressure aseptic technique in concert with currently available CSTDs. In one lesson, we provide kits for each participant to compound one simulated dose with a few different devices using either red dye or fluorescein. At first, the students are given little training and no practice and we invariably find many lapses in technique and device failures. This demonstrates the importance of comparing the devices and understanding the training needed to use them correctly; this is not an intuitive process.

The main risk of improper CSTD use is that failures will result in drug leakage—the exact thing you are trying to prevent. Frequent monitoring of use by a compounding pharmacist or lead technician is one method of bolstering compliance and competency. With more facilities adopting separate or remote compounding areas, as directed by USP <797>, there is an increasing lack of actual pharmacists present in the compounding area. While there are dose-tracking programs that use digital camera technology to allow for remote checking of the compounding steps, the still camera shots do not monitor technique, so other technology is needed. Establishing a protocol for swabbing surfaces for drug residue may be the long-term answer, but as yet that technology is not readily available and is quite expensive. A new technology similar to radiation exposure badges is really needed to indicate contamination.

PP&P: What points should be covered in annual training regarding the correct use of closed-system transfer devices?
LP: OSHA, NIOSH, ASHP, and USP <797> all include initial training and documentation of competence for handling hazardous drugs. Competency should be judged based on demonstration of required skills to perform the job and objective tests are the best approach in sterile compounding. Media fills and fingertip plating are good ways to document good aseptic technique. Using fluorescent material with black light or dye solutions in standard compounding performance tests allows an observer to review and critique hazardous drug compounding technique. All safety devices used in compounding, administering, waste management, and spill control—including CSTDs—must be part of annual training. Each employee should be able to explain the rationale for the safety equipment (including gowns, gloves, PECs, respiratory protection, waste containment, etc) as well as demonstrate competence in properly using these controls. Incorporating the use of media fills and CSTD components in quality assurance monitoring programs fulfills ongoing requirements for staff competency and for meeting the goals of sterile compounding.

PP&P: Are there technique challenges particular to closed-system transfer device usage within a compounding aseptic containment isolator (CACI)?
LP: It is important to note that, like any device, a CACI does not replace good aseptic technique in the compounding of sterile hazardous drugs. The same lapses in technique that produce drug residue in a biological safety cabinet (BSC) create contamination in a CACI. With a closed front PEC, you are less likely to find contamination on the floor in front of the PEC, but there is still the issue of drug residue on internal CACI work surfaces and transfer chamber surfaces. In addition, there is a potential to transfer this contamination to the waste areas and other areas when items are removed from the CACI. CACIs, due to their closed front, are difficult to clean and require placing cleaning tools into the work chamber through the transfer chamber.

Generally, the limitations of using CSTDs in CACIs are related to the fixed sleeve attachments. These access points tend to limit shoulder movement during compounding and may lead to some difficulty in attaching a CSTD vial cap to a vial.

During the CSTD selection process, each product should be demonstrated in a CACI to judge its appropriateness in this PEC. As the different CSTD systems vary as to the method and force required in capping, this should be an additional evaluation criteria. If the CACI is newly acquired, the CSTD manufacturer may be able to provide recommendations to improve the handling of the compounding devices within the CACI.

PP&P: How should pharmacy management address general staff reluctance to use a new system or complaints that usage of CSTDs slows compounding or administration processes too much?
LP: Most CSTD users report that an increase in processing time is an ephemeral effect. Once staff is fully trained and experienced with the devices, there tends to be little difference. The real issue here is whether the staff understands the risk of rushing compounding of chemotherapy doses and the fact that a large number of studies have documented hazardous drug residue on work surfaces, trash cans, phones, computers, elevator buttons, gowns, gloves, shoes and clothing, and in the urine of workers. There is a strong correlation that poor technique in compounding and other handling is responsible for this contamination. Once the staff understands the risks of adverse effects to their own health, there should be no resistance to using safety products such as CSTDs. The Hazard Communication Standard requires that employers inform workers of all hazards they may come in contact with and provide appropriate training and devices to reduce the risk of occupational exposure. This awareness will translate to better compliance.

Lastly, staff should be involved in the selection process and in determining the proper CSTD system for their particular setting. This buy-in empowers the adoption of all changes. Ultimately, studies are showing that surface contamination is transferred to many types of workers, not just compounding or infusion staff. Staff members who refuse to use appropriate safety practices will certainly contribute to drug contamination on surfaces and expose fellow employees to the resultant hazards. It is imperative that staff be held accountable for adhering to work practices and appropriate safety requirements. These should be addressed in periodic work appraisals and evaluations that determine financial merit increases.
 
Luci A. Power, MS, RPh, is an independent lecturer and consultant on pharmacy IV and hazardous drug systems. She was with the department of pharmaceutical services at the University of California Medical Center in San Francisco for over 25 years serving in various capacities, including Senior Pharmacist and Manager of the Parenteral Support Services, and Manager of IV Additive Services where she was responsible for in-patient chemotherapy and other hazardous drug compounding. Luci is a primary author of both the 1985 and 1990 ASHP Technical Assistance Bulletins on Handling Cytotoxic and Hazardous Drugs; lead author of the 2006 ASHP Guidelines on Handling Hazardous Drugs and first author of the ASHP Safe Handling of Hazardous Drugs Video Training Program. Luci is an original member of the National Institute for Occupational Safety and Health (NIOSH) working group on hazardous drugs and an author of the 2004 NIOSH Alert: Preventing Occupational Exposures to Antineoplastics and Other Hazardous Drugs in Health Care Settings.