Hospital personnel are increasingly aware of the risks associated with occupational exposure to antineoplastic drugs, both during the preparation and administration of these hazardous agents. However, numerous studies confirm that, despite having developed standard safety procedures, contamination still occurs in practically all facilities where antineoplastic drugs are handled [1-6].

Thus, with today’s rapid expansion of chemotherapy services, all efforts to minimize potential risks of exposure to these drugs are taken into consideration.

When considering safe handling of antineoplastic agents, all stages of chemotherapy production must be taken into account as an inseparable chain: from delivery of the drugs to preparation areas, to their reconstitution, through to their delivery to oncology departments, administration to patients and, finally, to their disposal after application. Alongside this, there is a risk that these hazardous agents can be released into the environment leading to exposure of workers.

When antineoplastic drugs are delivered, safety procedures can be optimized by using the correct labelling for transporting hazardous products. ESOP provides a tool to facilitate this: the ‘yellow hand’ label. This symbol indicates the hazard with a warning to all people who could come into contact with cytotoxic drugs during their transportation; it is designed to be easily understood even by an untrained person.

Preparation of antineoplastic drugs is a complex process. Numerous studies have shown that aseptic manipulation using the classical syringe and needle technique almost always results in contamination [7]. Therefore, every possible way of preventing workplace contamination with cytotoxic drugs should be considered. One of the best strategies to achieve this is to prevent the hazardous products escaping into the environment. For this purpose, special devices designed for safe handling of antineoplastic drugs can be helpful.

Over the last ten years, medical devices for reconstitution and administration of antineoplastic drugs have been developed and improved upon. They have developed from classical needles and syringes, to early spikes with filters, to vented spikes with closed connections, and finally to the new era of devices called ‘closed systems’. At present, pharmaceutical companies promote various special devices designed for the reconstitution and administration of hazardous drugs. The main purpose of these devices is to support safe handling of the drugs by keeping the hazard inside the device, preventing or minimizing any possible contamination. Most of these devices are widely used by pharmacists and other healthcare workers in daily practice. In addition, closed system devices are gaining in popularity.

There are numerous published studies concerning the evaluation of devices for hazardous drug handling [8-13]. However, most of these studies are focused on assessment of devices designed for drug preparation. Thus, it is necessary to evaluate devices in terms of their efficiency at every stage of chemotherapy production.

In a recent study, we have assessed environmental contamination and occupational exposure to antineoplastic drugs in the pharmacy and oncology ward before and after implementation of the closed system drug transfer device (CSTD).

Environmental contamination with cyclophosphamide (CP) and 5FU was assessed by taking wipe samples from several surfaces in the areas where antineoplastic drugs are prepared (pharmacy) and administered (chemotherapy ward). To establish occupational exposure, the excretion of CP was measured in the urine of pharmacists and nurses handling cytotoxic drugs, including CP. In addition, we also assessed the exposure of doctors who were not directly engaged in the preparation or to administration of these hazardous agents. In the study, eight hospital workers were involved—two pharmacists, four nurses and two doctors. One pharmacist prepared antineoplastic drugs while the other pharmacist assisted. All four nurses on the chemotherapy ward were engaged in the administration of the drugs. Two doctors did not handle the drugs but they had contact with treated patients.

Wipe and urine sampling were performed two times. The first time concerns monitoring of contamination and exposure during traditional preparation and administration procedures commonly used for many years. The second time concerns monitoring of contamination and exposure six months after the implementation of the CSTD.

Before implementation of the CSTD, the results show total spread of contamination with 5FU and CP in the nursing department, but also with CP in the pharmacy. Levels of contamination were higher for 5FU compared to CP, especially in the nursing department. The results of the wipe samples are presented in Table 1.

*Table 1 pending to upload.

Before implementation of the CSTD the results show exposure to CP of all pharmacists and doctors and almost all nurses. From 62 urine samples collected over 24 hr, CP was detected in 31 urine samples (50%) concerning two pharmacists, two doctors and three nurses. The total amount of CP excreted per worker ranged from 106 to 500 ng/24 hr, see Figure 1. The mean amount of CP excreted per worker on group basis was 234 ng/24 hr (doctors: 343 ng/24 hr, pharmacists: 239 ng/24 hr, nurses: 177 ng/24 hr). The highest amount of CP excreted was found for one doctor (500 ng/24 hr) and for one nurse (492 ng/24 hr). The amount of CP excreted in urine from the pharmacist who assisted in preparation (358 ng/24 hr) was higher than from the pharmacist who prepared the chemotherapy infusions (120 ng/24 hr). These results show that workers who were not directly involved in the preparation and administration of antineoplastic drugs were the most highly exposed ones.

*Figure 1 pending to upload.

After six months of using the CSTD, levels of surface contamination with 5FU and CP were lower. However, still high levels of contamination were found mainly for 5FU in the nursing room and to less extent with CP in the pharmacy. At most positions contamination remained at the similar level. Surprisingly, levels of contamination with 5FU were higher on the floor in the nursing room. This result indicates spillage during administration of the drugs. After consultation with nurses, it was found, that not all nursing personnel complied with procedures, and devices were not being used correctly. Nurses disconnected elements of the closed system, leading to spillage during connection and disconnection of chemotherapy preparations from patients.

The results for CP exposure after implementation of the CSTD show that the workers were still exposed to CP but the level was strongly reduced. However, it should be noticed that the decrease of exposure to CP does not have to be directly connected with the use of the CSTD, especially since surface contamination was still observed.

One drawback of this study is that it involved a small number of participants, so more research is needed. Nevertheless, there is sufficient evidence that personnel who are not directly involved in handling antineoplastic drugs can be exposed to these agents. Thus, all healthcare personnel, not only pharmacists, working in or near areas where cytotoxic drugs are handled must be made aware of the potential for contamination, and must improve safety procedures to reduce exposure.

This goal requires a continuous effort in investigation and research to introduce new approaches such as evaluation of different self-contained systems, assessment and validation of specific and general procedures, and their implementation in the daily routine of hospital departments. Adequate education and training of the staff members involved is essential.

Safe handling procedures should be implemented in all areas where antineoplastic drugs are delivered, stored, prepared, administered, and disposed of in order to reduce contamination in the workplace and the resulting exposure to healthcare workers.

The possibility of developing devices for the whole handling procedure must be addressed. It is important that other hospitals, particularly those in other countries, are involved in future research in this area in order to collect data on an issue that can no longer be ignored. The awareness of establishing processes and procedures has to be increased among other hospital workers, not only pharmacists, nurses, technicians and doctors.

Devices can be helpful in supporting safe handling of antineoplastic drugs, but they must be used correctly by adequately trained personnel, otherwise they become useless.

Acknowledgement

The authors would like to thank Dr Paul JM Sessink for analytical support and reviewing the manuscript.

Authors

Ewelina Korczowska, MPharm
Hanna Jankowiak-Gracz, PharmD

Clinical Hospital of Lord’s Transfiguration
University of Medical Sciences
PL-61848 Poznan, Poland

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