Owing to their non-selective nature, anti-cancer drugs affect both cancerous and non-cancerous cells and present a major health risk to healthcare staff working with them. This project was conducted at Derriford Hospital, Plymouth, to investigate the extent of contamination with anti-cancer drugs on work surfaces and the environmental emissions of these drugs. In the Isolator study, surface contamination arising from the preparation of five anticancer drug infusions (epirubicin, fluorouracil, cisplatin, oxaliplatin and carboplatin) in a pharmaceutical isolator and external surfaces of infusion bags and syringes using a conventional syringe and needle technique was investigated and compared with that obtained using a closed system drug transfer device (Tevadaptor). Wipe samples were taken for a period of one week from pre-defined areas in a pharmaceutical isolator and from the surface of prepared Intra-Venous (IV) infusion bags and pre-filled syringes to obtain baseline data. Gloves and preparation mats used during this period were also collected. Following a one-week operator familiarisation period, the Tevadaptor device was then introduced for cytotoxic preparation and wipe-sampling of surfaces and collection of consumables was continued for a further week (intervention period). The samples obtained were then analysed by HPLC and ICP-MS. The baseline contamination data from Tevadaptor isolator study was undetected to 0.9 ng cm-2 (epirubicin), undetected to 3.58 ng cm-2 (5-FU) and 0.05-0.92 ng cm-2 (Pt) in the wipe samples from the pharmaceutical isolator surfaces; amounts on glove samples were 1100-6100 ng/glove (epirubicin), 300-8100 ng/glove (5-FU) and 1-6 ng/glove (platinum). During the intervention phase isolator surface contamination was not detected in all samples for 5-FU and epirubicin and platinum was detected on the isolator surfaces in the range of 0.002-0.09 ng cm-2. The use of Tevadaptor resulted in a reduction of contamination on external surfaces by a factor of 10 or more for all marker drugs. A ward study investigated the surface contamination in the oncology out-patient department caused by cisplatin, oxaliplatin, carboplatin and gemcitabine. The study compared the effect of using the Tevadaptor to prepare and administer anticancer drugs infusions on ward surface contamination to the current UK standard practice. A questionnaire was also distributed to participating staff members to assess the user-friendliness of Tevadaptor. Wipe samples were taken from pre-defined areas from the oncology out-patients department and gloves used by nursing staff for assembly and administration of the above drugs were also collected. Sample collection followed a similar schedule to the Tevadaptor isolator study. The baseline ward surface contamination ranged from undetected to 4.97 ng cm-2 (gemcitabine) and 3.1 ng cm-2 (platinum). In the case of gloves used by nursing staff the levels of contamination ranged from undetected to 1251 ng/glove (gemcitabine) and 405.4 ng/glove (platinum). The contamination on ward surfaces during the intervention phase ranged from undetected to 3.21 ng cm-2 (gemcitabine) and 2.69 ng cm-2 (platinum) and contamination levels on gloves ranged from undetected to 9252 ng/glove (gemcitabine) and 1319 ng/glove (platinum). During the intervention phase there was a reduction in frequency of contamination, even though the total amount of surface contamination by anticancer drugs did not always decrease in comparison to baseline data, presumably due to unaccounted spillages. A drain study investigated the presence of platinum in hospital wastewater as a measure of contamination caused by the excretion of platinum-based anticancer drugs by patients. Platinum was measured over a three week period in one of the main drains and in the effluent of the oncology ward. The study showed the presence of measurable quantity of platinum which ranged from 0.02 to 140 μg L-1 in the oncology effluent and 0.03 to 100 μg L-1 in the main drain. Data from this study was coupled with published measurements on the removal of the drugs by conventional sewage treatment and then concentration of platinum arising from each drug was predicted in recipient surface waters as a function of water flow rate. Although predicted concentrations were below EMEA guidelines warranting further risk assessment, the presence of potentially carcinogenic, mutagenic and teratogenic substances in surface waters is cause for concern. The results showed that a closed system drug transfer device (CSTD) used in conjunction with an isolator is highly efficient in reducing surface contamination with anti-cancer drugs. However, despite current best practice contamination on ward surfaces remained even after the use of a CSTD. Nursing as well as healthcare staff should be educated of these results and the risks of occupational exposure to low levels of anti-cancer drugs and the use of PPE should be emphasised. Results of the drain study form the basis of preliminary estimates of the likely concentrations of platinum-based drugs in surface waters and their potential environmental impacts.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.