teaser
Yaakov Cass
MSc FRPharmS
Regional Pharmaceutical Officer
Central District
Ministry of Health
Ramle
Menahem Kraus
PhD
Director of Research and Development
Teva Medical Ltd
Ashdod
Israel
Cytotoxics have been in clinical use for decades and are of great importance in the treatment of cancer. Typically, cytotoxic drugs affect cell growth and proliferation, binding directly to genetic material in the cell nucleus or affecting cellular protein synthesis with little differentiation between normal and cancerous cells.(1) The International Agency for Research on Cancer (IARC), part of the World Health Organization, now lists nine chemotherapy drugs and two combinational therapies as known human carcinogens. Another nine drugs are listed as “probable” and ten more as “possible” carcinogens.(2) There is no way to accurately estimate how much harm has been caused by the careless handling of these drugs and in many instances the connection between their unsafe handling and disease is never made.(3-12) Countless reams have been written on the importance of safe handling of cytotoxic drugs and nowadays it would be hard to find a hospital pharmacist who was not well aware of the inherent dangers of handling cytotoxics without the recommended precautionary measures.(13-19) Despite this huge amount of knowledge within the pharmacy fraternity, the US National Institute for Occupational Safety and Health (NIOSH) recently issued a detailed alert stating that cytotoxic drugs are carcinogenic and despite current safety provisions they still pose a risk to nurses, pharmacists and others who handle them.(20-25) The alert strongly recommends the use of closed-system protective devices after researchers found that closed systems significantly reduced contamination on work surfaces and in employee’s urine samples.(26-28)
In an effort to reduce occupational exposure from cytotoxics, Israeli company Teva Medical Ltd has developed the new Tevadaptor system for safe handling of such drugs. The system effectively and selectively prevents the ingress of environmental contaminants into drug containers and the spread of cytotoxic drugs – whether as solid, liquid, aerosol or vapour – out of drug containers and into the environment.
The device has several unique features that make it both effective and user-friendly, and thus conducive to a high level of user compliance. The combination of a vented containment system and an innovative connection/disconnection mechanism enhances its safety. The system claims full compliance with both published NIOSH and soon-to-be-published ISOPP guidelines for hazardous drug handling systems.(21,29)
The device has three main components: the vial adaptor, infusion bag adaptor and syringe adaptor (see Figures 1-3). All connections are straightforward. In use, each adaptor is first connected to its respective container. The vial adaptor is clicked onto a vial, the Luer-lock syringe is screwed into the syringe adaptor and the bag adaptor is spiked into the bag as needed. User and environment protection by the device are fully automatic, obviating any need for the user to undertake planning, calculations or measurements for the system to function properly. The system is designed to be foolproof and eliminates accidental needlestick injury.
[[HPE_Fig1_70]]
[[HPE_Fig2_70]]
[[HPE34_Fig3_71]]
Air handling by Tevadaptor is automatic, requiring no action by the user. Pressure equalisation inside the vial occurs immediately when the vial is inserted into the vial adaptor. Pressure in the vial remains equal to the ambient pressure during both filling and emptying of the vial. Any air introduced into the system is sterilised by a sterilising-grade membrane in the vial adaptor. The venting system in Tevadaptor is unique in that it is the only vented system that protects the user and the environment not only from solid particles and aerosol but also from toxic vapours. This is achieved by a combination of a hydrophobic microporous membrane and a charcoal cloth. The membrane blocks particles and liquid droplets and the charcoal effectively adsorbs any drug vapour that permeates through the membrane. Hence, it is in fact a vented containment system.
The mechanical system by which the components are connected to each other is also unique in that it requires only a simple “click-on” for connection and a “press-and-pull” action for disconnection. Protection against leakage is automatic. The device design ensures that upon disconnection of any two Tevadaptor components, both are effectively sealed, eliminating drug leakage.
The system enables bag preparation for infusion using partial, full or multiple vials. Small-cap vials can be used with the same vial adaptor after connection to an adapting converter (see Figure 4). Furthermore, the system enables safe transfer of drug-filled syringes or bags from the pharmacy to the administration area. Safe administration from a syringe into an infusion line is assured by using an additional adaptor.
[[HPE34_Fig4_71]]
Laboratory and environmental testing were performed to ensure the efficacy of Tevadaptor. Tests included maintenance of sterility, venting system containment and environmental wipe tests. Vial and bag sterility maintenance were determined with positive and negative controls, demonstrating solution sterility for at least 14 days. Sterility is fully maintained for more than the anticipated duration of use of either a drug vial or a reconstituted infusion bag. This means it is unnecessary to keep partially used vials or infusion bags under sterile conditions after preparation. Twelve units of Tevadaptor vial adaptor were challenged with cyclophosphamide vapour by passing 90l of nitrogen through a cyclophosphamide-
containing vial equipped with a Tevadaptor at a rate of 0.5l/min. Tevadaptor units were tested after different sterilisation conditions: nonsterile, sterilised with ethylene oxide and sterilised with gamma radiation. Two units without filtration system were used as controls. In the controls there was a passage of 28ng and 32g of cyclophosphamide/90l of nitrogen, while in all Tevadaptor test units there was zero passage of cyclophosphamide. In total, 75 Tevadaptor units were used in an environmental contamination test. The vial contents were spiked with 99Tc for radioactive analysis of possible liquid spill. Testing was performed immediately after each preparation. Used gloves and pads were wiped and tested for radioactivity using scintillation counting. All units were within the local standard of 100nl per preparation (one drop equals 50,000nl). The results indicate that Tevadaptor achieves its stated aims, providing an efficient and effective hazardous-drug containment system.
References
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