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HAZARDOUS DRUG EXPOSURES IN HEALTHCARE

Environmental Sampling, Decontamination, Protective Equipment, Closed System Transfer Devices, and Work Practice

Environmental Sampling

Environmental sampling is a relatively new approach used to determine the level of workplace contamination by antineoplastic agents. The procedure has been used extensively in other situations, especially for monitoring contamination by radioactive materials. Typically, work surfaces are sampled with a moistened wipe and the material is extracted and analyzed for specific antineoplastic agents. Currently, it is possible to identify and quantitate six to eight agents with this technique.

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Decontamination and Deactivation of Antineoplastic Agents

Several reports have dealt with methods for the decontamination and/or deactivation of antineoplastic agents. Although bleach (hypochlorite) is often recommended for the decontamination purposes, it is not effective with all classes of agents. Therefore, it cannot be assumed that cleaning with bleach solutions will destroy all types of antineoplastic agents. Some antineoplastic drugs are listed by the US Environmental Protection Agency as Hazardous waste and must be disposed of accordingly (see 40 CFR 261.33).

  • AIHA Healthcare Working Group Hazardous Drugs Project Team. Chemotherapy hood decommissioning for disposal or recycling. Fact sheet. Approved by AIHA Board: October 17, 2016. Falls Church, VA: American Industrial Hygiene Association (AIHA).
  • Anastasi M, Rudaz S, Lamerie TQ, Odou P, Bonnabry P and Fleury-Souverain S. Efficacy of two cleaning solutions for the decontamination of 10 antineoplastic agents in the biosafety cabinets of a hospital pharmacy. Ann Occup Hyg. 2015; 59:895-908.
  • Barek J, Cvaccka J, Zima J, De Meo M, Laget M, Michelon J and Castegnaro M. Chemical degradation of wastes of antineoplastic agents amsacrine, azathioprine, asparaginase and thiotepa. Ann Occup Hyg. 1998; 42:259-266.
  • Bassi MD and Moretton J. Mutagenicity of antineoplastic drug residues treated in health care waste autoclave. Bull Environ Contam Toxicol. 2003; 71:170-175.
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  • Bohlandt A, Groeneveld S, Fischer E and Schierl R. Cleaning Efficiencies of three cleaning agents on four different surfaces after contamination by Gemcitabine and 5-fluorouracile. J Occup Environ Hyg. 2015; 12:384-392.
  • Castegnaro M, De Meo M, Laget M, Michelon J, Garren L, Sportouch MH and Hansel S. Chemical degradation of wastes of antineoplastic agents 2: Six anthracyclines: idarubicin,doxorubicin, epirubicin, pirarubicin, aclarubicin, and daunorubicin. Int Arch Occup Environ Health. 1997; 70:378-384.
  • Chu WC, Hon C-Y, Danyluk Q, Chua PPS and Astrakianakis G. Pilot assessment of the antineoplastic drug contamination levels in British Columbia hospitals pre- and post-cleaning. J Oncol Pharm Practice. (Published on line 2011; DOI: 10.1177/1078155211402106).
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  • Gohma H, Inoue Y, Asano M and Sugiura SI. Testing the degradation effects of three reagents on various antineoplastic compounds. J Oncol Pharm Practice. 2014; (Epub ahead of print) DOI: 10.1177/1078155214530175.
  • Hansel S, Castegnaro M, Sportouch MH, De Meo M, Milhavet JC, Laget M and Dumenil G. Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide and melphalan. Int Arch Occup Environ Health. 1997; 69:109-114.
  • Hon CY, Chua PPS, Danyluk Q and Astrakianakis G. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study. J Oncol Pharm Pract. Published online 8 August 2013.
  • Hon CY, Chua PPS, Danyluk Q and Astrakianakis G. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study. J Oncol Pharm Practice. 2014; 20:210-216.
  • Lamerie TQ, Nussbaumer, S, Décaudin B, Fleury-Souverain S, Goosens J-F, Bonnabry P and Odou P. Evaluation of decontamination efficiency of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. Ann Occup Hyg. 2013; 57:456-469.
  • Lé LMM, Jolivot PA, Yaye HS, Rieutord A, Bellanger A, Pradeau D, Barbault-Foucher S and Caudron E. Effectiveness of cleaning of workplace cytotoxic surface. Int Arch Occup Environ Health. 2013; 86:333-341.
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  • Roberts S, Khammo N, McDonnell and Sewell GJ. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Practice. 2006; 12:95-104.
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  • Touzin K, Bussières JF, Langlois É, Lefebvre M and Gallant C. Cyclophosphamide contamination observed on the surface of drug vials and the efficacy of cleaning on vial contamination. Ann Occup Hyg. 2008; 1-7.
  • Touzin K, Bussières JF, Langlois É, Lefebvre M and Métra A. Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg. 2010; 54:351-359.
  • Wren AE, Melia CD, Garner ST and Denyer SP. Decontamination methods for cytotoxic drugs. 1. Use of a bioluminescent technique to monitor the inactivation of methotrexate with chlorine-based agents. J Clin Pharm and Therap. 1993; 18:133-137.

Evaluation of Protective Equipment for Handling Antineoplastic Agents

The most often used type of protective equipment for handling antineoplastic agents is gloves. Typically latex and other materials have been employed for this use. However, with the concern over latex allergies, newer materials are being marketed and evaluated for use with these agents. Protective gowns are another piece of equipment that is commonly used in the handling of antineoplastic agents. This section also deals with biological safety cabinets and closed system devices used in the preparation of antineoplastic drugs.

  • Benoit L, Cheynel N, Ortega-Deballon P, Di Giacomo G, Chauffert B, Rat P. Closed hyperthermic intraperitoneal chemotherapy with open abdomen: a novel technique to reduce exposure of the surgical team to chemotherapy drugs. Ann Surg Oncol. 2007; 15:542-546.
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  • Connor TH. An evaluation of the permeability of disposable poylpropylene-based protective gowns to a battery of cancer chemotherapy drugs. Appl Occup Environ Hyg. 1993;8:785-789.
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  • Connor TH. Permeability of nitrile rubber, latex, polyurethane, and neoprene gloves to 18 antineoplastic drugs. Am J Health-Syst Pharm. 1999; 56: 2450-53.
  • Connor TH and Xiang Q. The effect of isopropyl alcohol on the permeation of gloves exposed to antineoplastic agents. J Oncol Pharm Practice. 2000; 6: 109-114.
  • Connor TH. Using PPE to prevent occupational exposure to antineoplastic and other hazardous drugs. Pharm Purchasing & Products. 2006; 2:4-6.
  • Connor TH. Personal protective equipment for use in handling hazardous drugs. Pharm Purchasing & Products. 2006; 3:2-6.
  • Connor, TH, Power LA, Massoomi F and Polovich M. White glove test for safety. ECNews. 2015; 18: 6-7, 11.
  • Connor TH, Power LA, Massoomi F and Polovich M. Are gloves and gowns safe for handling chemotherapy? Pharm Purchasing and Products. 2015; 12:2,4.
  • Dinter-Heidorn H and Carstens G. Comparative study on protective gloves for handling cytotoxic medications: A model study with carmustine. Pharmaceutisch Weekblad Sci. 1992; 14:180-184.
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  • Donner AL. Possible risk of working with antineoplastic drugs in horizontal laminar flow hoods (letter). Am J Hosp Pharm. 1978; 35:900.
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  • Furlow B. How to improve the safety of chemotherapy administration. Oncology Nurse Advisor. 2010; 21-25.
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  • Graeve C, McGovern PM, Arnold S and Polovich M. Testing an intervention to decrease healthcare workers’ exposure to antineoplastic agents. ONF 2017; 44(1):E10–E19 (e-pub; doi: 10.1188/17.0NF.E10-E19).
  • Graeve CU, McGovern PM, Alexander B, Church T, Ryan A and Polovich M. Occupational exposure to antineoplastic agents: an analysis of health care workers and their environments. Workplace Health and Safety. 2016 (e-pub; doi: 10.117712.165079916662660).
  • Gross ER and Groce DF. An evaluation of nitrile gloves as an alternative to natural rubber latex for handling chemotherapeutic agents. J Oncol Pharm Practice. 1998; 4:165-168.
  • He BY, Mendelsohn-Victor K, Mccullagh MC and Friese CR. Personal protective equipment use and hazardous drug spills among ambulatory oncology nurses. ONF 2017; 44: 60–65.
  • Hennessy KA and Dynan J. Improving compliance with personal protective equipment use through the model for improvement and staff champions. Clin J Oncol Nurs. 2014; 18:497-500.
  • Klein M, Rau S, Samev N and Carstens G. Protection offered by selected medical gloves made of either latex or a synthetic elastomer against exposure to nine cytotoxic agents. European Hosp Pharm. 1999; 5:152-158.
  • Klein M, Lambov N, Samev N and Carstens G. Permeation of cytotoxic formulations through swatches from selected medical gloves. Am J Health-Syst Pharm. 2003; 1006-1011.
  • Korinth G, Schmidt K., Midasch O, Boettcher M I, Angerer J and Drexler H. Investigations on permeation of mitomycin C through double layers of natural rubber gloves. Ann Occup Hyg. 2007; 51:593-600.
  • Krämer I, Federici M. Kaiser V and Thiesen J. Media-fill simulation tests in manual and robotic aseptic preparation of injection solutions in syringes. J Oncol Pharm Pract. 2014 (epub. DOI: 10.1177/1078155214565123).
  • Labella CJ. Does your pharmacy have a compounding isolator? Am J Health-Syst Pharm. 2007; 64:855-858.
  • Lalande L, Galy G, Dussossoy E, Noyel JE and Pivot C. Evaluation of safe infusion devices for antineoplastic administration. J Infus Nurs. 2012; 35:321-327.
  • Laidlaw JL, Connor TH, Theiss JC Anderson RW and Matney TS . Permeability of latex and polyvinyl gloves to 20 antineoplastic drugs. Am J Hosp Pharm. 1984; 41:2618-2623.
  • Laidlaw JL, Connor TH, Theiss JC, Anderson RW and Matney TS. Permeability of four disposable protective-clothing materials to seven antineoplastic drugs. Am J Hosp Pharm. 1985; 42:2449-2454.
  • Landeck L, Gonzalez E and Koch OM. Handling chemotherapy drugs – do medical gloves really protect? Int J Cancer. 2014; (Epub ahead of print) DOI: 10.1002/ijc.29058.
  • Lecordier J, Plivard C, Gardeux M, Daouadi K and Lehet J-J. To create a cleanroom controlled environement using a mobile air decontamination unit for the preparation of antineoplastic drugs. J Oncol Pharm Pract. 2014. (epub. DOI: 10.1177/1078155214565125)
  • Ledford A and Wetzel B. Constructing an oncology pharmacy. Pharm Purch Prod. May 2017; 14 (5):10-15.
  • Mader RM, Rizovski B, Steger GG Moser K, Rainer H and Dittrich C. Permeability of latex membranes to anti-cancer drugs. Int J Pharmaceut. 1991; 68:151-156.
  • Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value and limitations of protective gloves in medical health service:Part I. Dermatol Nurs. 1996; 8:160-164.
  • Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value and limitations of protective gloves in medical health service:Part II. Dermatol Nurs. 1996; 8:287-295.
  • Mellström GA, Wrangsjö K, Wahlberg JE and Fryklund B. The value and limitations of protective gloves in medical health service:Part III. Dermatol Nurs. 1996; 8:345-355.
  • Nygren O. Wipe samples as a tool for monitoring aerosol deposition in workplaces. J Environ Monit. 2006; 8;49-52.
  • Odraska P, Dolezalova L, Kuta J, Oravec M, Piler P and Blaha L. Evaluation of the efficacy of additional measures introduced for the protection of healthcare personnel handling antineoplastic drugs. Ann Occup Hyg. 2012; August 27 (Epub ahead of printing) DOI:10.1093/annhyg/mes057.
  • Peters GF, McKeon MK and Weiss WT. Potential for airborne contamination in turbulent- and unidirectional-airflow compounding aseptic isolators. Am J Health-Syst Pharm. 2007; 64:622-631.
  • Sewell GJ. The use of isolators for cytotoxic drug handling in hospital pharmacies. Eur J Parent Soi. 1999; 4:55-59.
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  • Slevin ML, Ang LM, Johnston A and Turner P. The efficiency of protective gloves used in the handling of cytotoxic drugs. Cancer Chemother Pharmacol. 1984; 12:151-53.
  • Stajich GV, Barnett CW, Turner SV and Henderson CA. Protective measures used by oncologic office nurses handling parenteral antineoplastic agents. Oncol Nurs Forum. 1986; 13:47-49.
  • Stoikes ME, Carlson JD, Farris FF and Walker PR. Permeability of latex and polyvinyl chloride gloves to fluorouracil and methotrexate. Am J Hosp Pharm. 1987; 44:1341-1346.
  • Thomas PH and Fenton-May V. Protection offered by various gloves to carmustine exposure. The Pharm J. 1987; 238:775-777.
  • Thomsen K and Mikklesen HI. Protective capacity of gloves used for handling nitrogen mustard. Contact Derm. 1975; 1:268-269.
  • Tomas ME, Kundrapu S, Thota P, Sunkesula VCK, Cadnum JL, Mana TSC, Jencson A, O’Donnell M, Zabarsky TF, Hecker MT, Ray AJ, Wilson BM and Donskey CJ. Contamination of health care personnel during removal of personal protective equipment. JAMA Intern Med. 2015 (Epub ahead of print). DOI: 10.1001/jamainternmed.2015.4535.
  • Tompa A, Jakab M, Biro A, Magyar B, Fodor Z, Klupp T and Major J. Chemical safety and health conditions among Hungarian hospital nurses. Ann NY Acad Sci. 2006; 1076:635-648.
  • Villa AF, El Balkhi S, Aboura R, Sageot H, Hasni-Pichard H, Pocard M, Elias D, Joly N, Payen D, Blot F, Poupon J and Garnier R. Evaluation of oxaliplatin exposures of healthcare workers during heated intraperitoneal perioperative chemotherapy (HIPEC). Ind Health. 2015; 53:28-37.
  • Vyas N, Yiannakis D, Turner A and Sewell GJ. Occupational exposure to anti-cancer drugs: A review of effects of new technology. J Oncol Pharm Pract. 2014; 20:278-287.
  • Wagner JT. Ensure safe use of CAIs and CACIs. Pharm Purchasing and Products. 2014; 11 (12):12,14.
  • Wagner JT. Considerations for choosing a primary engineering control for compounding sterile products. Int J Pharm Comp. 2005; 9:284-290.
  • Wallemacq PE, Capron A, Vanbinst R, Boeckmans E, Gillard J and Favier B. Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions. Am J Health-Syst Pharm. 2006; 63:547-556.

Robotics

  • Chen WH, Shen LJ, Guan RJ and Wu FL. Assessment of an automatic robotic arm for dispensing of chemotherapy in a 2500-bed medical center. J Formos Med Assoc. 2013; 112:193-200.
  • Krämer I, Federici M, Kaiser V and Thiesen J. Media-fill simulation tests in manual and robotic aseptic preparation of injection solutions in syringes. J Oncol Pharm Practice. 2014 (Epub ahead of print). DOI: 10.1177/1078155214565123.
  • Masini C, Nanni O, Antaridi S, Gallegati D, Marri M, Paolucci D, Minguzzi M and Altini M. Automated preparation of chemotherapy: quality improvement and economic sustainability. Am J Health-Sys Pharm. 2014; 71:579-585.
  • McLeod M, Zochowska A, Leonard D, Crow M, Jacklin A, Franklin BD. Comparing the upper limb disorder risks associated with manual and automated cytotoxic compounding: a pilot study. Eur J Hos Pharm. 2012; 19:293-298.
  • Nurgat Z, Faris D, Mminah M, Vibar A, AL-Jazairi A, Ewing S, Ashour M, Qaisi SK, Balhareth S and AL-Jedai A. A three-year study of a first-generation chemotherapy-compounding robot. Am J Health-Syst Pharm. 2015; 72:1036-1045.
  • Palma E and Bufarini C. Robotized compounding of oncology drugs in a hospital pharmacy. Int J Pharm Compd. 2014; 18:358-364.
  • Schierl R, Masini C, Groeneveld S, Fischer E, Bohlandt A, Rosini V and Paolucci D. Environmental contamination by cyclophosphamide preparation: comparison of conventional manual production in biological safety cabinet and robot-assisted production by APOTECAchemo. J Oncol Pharm Practice. 2016; 22:37-45.
  • Seger AC, Churchill WW, Keohane CA, Belisle CD, Wong ST, Sylvester KW, Chesnick MA, Burdick E, Wien MF, Cotugno MC, Bates DW and Rothschild JM. Impact of robotic antineoplastic preparation on safety, workflow, and costs. J Oncol Pract. 2012; Nov 1:344-350.
  • Sessink PJM, Leclercq GM, Wouters DM, Halbardier L, Hammad C and Kassoul N. Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation. J Oncol Pharm Practice. 2014; (Epub ahead of print) DOI: 10.1177/1078155214522840.
  • Yaniv AW and Knoer SJ. Implementation of an i.v.-compounding robot in a hospital-based cancer center pharmacy. Am J Health-Syst Pharm. 2013; 70:2030-2037.

Closed System Drug-Transfer Devices (CSTDs) and Similar Devices

NIOSH defines a closed system drug transfer device 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.” There are several CDTDs currently available from different manufacturers. CSTDs have been shown to reduce the levels of surface contamination present where antineoplastic drugs are handled and to reduce the percentage of wipe samples that have detectable amounts of antineoplastic drugs.

  • Berdi F, Powell MF, Sanz C, Gonzalez R and Massoomi F. Assessing the efficiency of CSTDs for compounding. Pharm Purch Products. 2015; 12:4-7.
  • Berdi F, Powell M, Sanz C, Gonzalez R and Massoomi F. Assessing the efficiency of CSTDs for compounding. Pharm Purch Prod. July 2015; 12 (7) Supp.
  • Connor TH, Anderson RW, Sessink PJ and Spivey SM. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health-Syst Pharm. 2002; 59:68-72.
  • Clark BA and Sessink PJM. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Prac. 2013; 19:99-104.
  • De Ausen L, DeFreitas EF, Littleton L and Lustik M. Leakage from closed-system transfer devices as detected by a radioactive tracer. Am J Health-Syst Pharm. 2013; 70:619-623.
  • De Prijck K, D’Haese E, Vandenbroucke J, Coucke W, Robays H and Nelis HJ. Microbiological challenge of four protective devices for the reconstitution of cytotoxic agents. Lett Appl Micro. 2008; 47:543-548.
  • Edwards MS, Solimando DA, Grollman FR, Pang JL, Chasick AH, Hightman CM, Johnson AD, Mickens MG and Preston LM. Cost savings realized by use of the PhaSeal® closed-system transfer device for preparation of antineoplastic agents. J Oncol Pharm Pract. 2013; 19:338-347.
  • Favier B, Labrosse H, Gilles-Afchain L, Cropet C, Perol D, Chaumard N, Latour JF and Hild P. The PhaSeal® system: impact of its use on workplace contamination and duration of chemotherapy preparation. J Oncol Pharm Practice. 2011; 18:37-45.
  • Forges F, Simoens X and Chauvin F. Comparative parallel assessment of a transfer device in reducing 5-fluorouracil environmental contamination inside positive air pressure isolators. J Oncol Pharm Practice. 2011; 17:61-67.
  • Garrigue P, Montana M, Ventre C, Gauthier-Villano L, Pisano P and Pourroy B. Safe cytotoxic drug preparation using closed-system transfer device: technical and practical evaluation of a new device (Vialshield/Texium) comparatively to a reference one (Phaseal). Int J Pharm Compounding. 2016; 20:148-154.
  • Gomez-Alvarez S, Porta-Oltra B, Hernandez-Griso M, Perez-Labana F and Climente-Marti M. Evaluacion de dos sistemas cerrados en el proceso de elaboracion de quimioterapia parenteral. Farm Hosp. 2016; 40:36-43.
  • Haifler M, Lang E, Sabler I, Gutman Y, Lindner A and Zisman A. Increasing medical staff safety by using a closed system for intravesical instillation of mitomycin C. Urology. 2010; 76:649-651.
  • Hama K, Kitada N, Fukushima K, Hashida T and Kataoka K. Investigation on residual-related error and the effect of solution properties using protective devices for the reconstitution of cytotoxic agents in actual situations. J Oncol Pharm Practice. 2011; 17:55-60.
  • Harrison BR, Peters BG and Bing MR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health-Syst Pharm. 2006; 63:1736-1744
  • Ho KV, Edwards MS, Solimando DA Jr, Johnson AD. Determination of extended sterility for single-use vials using the Phaseal closed-system transfer device. J Hematol Oncol Pharm. 2016; 6:46-50.
  • Jorgenson JA, Spivey SM, Au C, Canann D, Ritter H and Smith B. Contamination comparison of transfer devices intended for handling hazardous drugs. Hosp Pharm. 2008; 43:723-727.
  • Jorgenson JA and Stevenson JG. Special Report: Closed-system drug-transfer devices: ONB classification and the draft NIOSH protocol. Pharm Pract News. June 2017; Supp:1-4.
  • Kelley L. Response to the study: ‘syringe plunger contamination by hazardous drugs: a comparative study’ by Stephen T Smith and Mark C Szlaczky. J Oncol Pharm Practice. 2014; 20:397-398.
  • Kicenuik K, Northrup N, Dawson A, Locke J, Villamil JA, Chretin J, Sfiligoi G, Clifford C, Rosenberg M, Hamilton T, Regan R, Parsons-Doherty M, Mallett C, Philibert J, Imperllizeri J and Hofmeister E. Treatment time, ease of ue and cost associated with use of Equashield™, PhaSeal®, or no closed system transfer device for administration of cancer chemotherapy to a dog model. Vet Comp Oncol. 2015 (Epub ahead of print). DOI: 10.1111/vco.12148.
  • Kopp B, Schierl R and Nowak D. Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health. 2013; 86:47-55.
  • Koraleski M, Massoomi F and Zock M. Evaluation of FDA-approved ONB closed-system transfer devices utilizing Cyclophosphamide as a marker. ICU Medical Inc. 2013; M1-1455 Rev.01.
  • Kunneva L. Closed system drug transfer devices for chemotherapy. Nursing. 2016; 46:67-68.
  • Lamerie TQ, Carrez L, Decaudin B, Bouchoud L, Goossens JF, Barthelemy C, Bonnabry P and Odou P. Multiple-test assessment of devices to protect healthcare workers when administering cytotoxic drugs to patients. J Oncol Pharm Practice. 2011; 18:191-200.
  • Le Garlantezec P, Rizzo-Padoin N, Aupee O, Lamand V, Broto H and Almeras D. Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m) Tc]. Ann Pharm Fr. 2011; 69:192-191 (French, English abstract).
  • Massoomi F. The evolution of the CSTD. Pharm Purchasing and Products. 2015; 12 (2): S1-S12.
  • Massoomi F and Eisenberg S. Pharmacy and nursing collaborate on CSTD training. Pharm Purchasing Prod. 2015; May:12-16.
  • Mayer J, Menetre S, Serrurier C, Delfour A and May I. Comparison of closed-system devices for the preparation of cytotoxic drugs. Le Pharmacien Hospitalier et Clinicien. 2011; 46:116-122. (French, English abstract)
  • Miyake T, Iwamoto T, Tanimura M and Okuda M. Impact of closed-system drug transfer device on exposure of environment and healthcare provider to cyclophosphamide in Japanese hospital. SpringerPlus. 2013; 2:273.
  • Mullot H, Blondeel S, Escalup L, Negellen S, Chenailler C, Pelloquin A and Courbard M. Interest and feasibility of Tevadaptor® and Phaseal® use in a centralized unit of antineoplastics preparation. Pharm Hosp. 2008; 43:189-199.
  • Nygren O, Gustavsson B, Strom L, Eriksson R, Jarneborn L and Friberg A. Exposure to anti-cancer drugs during preparation and administration. Investigations of an open and a closed system. J Environ Monit. 2002; 4:739-732.
  • Nygren O, Gustavsson B and Eriksson R. A test method for assessment of spill and leakage from drug preparation systems. Ann Occup Hyg. 2005; 49:711-718.
  • Nygren O, Olofsson E and Johansson L. Spill and leakage using a drug preparing system based on double-filter technology. Ann Occup Hyg. 2008; 52:95-98.
  • Nygren O, Olofsson E and Johannson L. NIOSH definition of closed-system transfer devices (Letter to the Editor). Ann Occup Hyg. 2009; 53:549.
  • Nyman H, Jorgenson J and Slawson MH. Workplace contamination with antineoplastic agents in a new cancer hospital using a closed-system drug transfer device. Hosp Pharm. 2007; 42:219-225.
  • Power LA. Closed-system transfer devices for safe handling of injectable hazardous drugs. Pharm Pract News. 2013;1-16.
  • Rosenthal M. CSTD buyers need advocacy help. Pharm Prac News. 2016; April 4.
  • Rosenthal M. CSTD test protocol stirs debate (Part 1) Pharm Pract News. February 2017; 44 (2):20-21.
  • Rosenthal M. Establishing procedures for testing CSTDs (Part 2). Pharm Pract News. March 2017; 44 (3):32-33.
  • Sanchez-Rubio Ferrrandez J, Lozano MC, Iglesias I, Sanchez-Rubio Ferrandez L, Rodriguez Vargas B and Moreno Diaz R. Use of a closed-system drug transfer device (PhaSeal®) and impact on preparation time. Int J Pharm Compd. 2012; 5:431-433.
  • Sessink PJM, Rolf M-AE and Ryden NS. Evaluation of the PhaSeal hazardous drug containment system. Hosp Pharm. 1999; 34:1311-17.
  • Sessink PJM, Connor TH, Jorgenson JA and 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 Practice. 2011; 17:39-48.
  • Sessink PJM, Trahan J and Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 hospital pharmacies following implementation of a closed-system drug transfer device. Hosp Pharm. 2013; 48:204-212.
  • Siderov J, Kirsa S and McLauchlan R. Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Pract. 2010; 16:19-25.
  • Sidikou O, Simon N, Sergent G, Vasseur M, Pinturaud M, Richeval C, Allorge D, Decaudin B and Odou P. In vitro assessment of a new extension set intended to reduce occupational exposure to antineoplastic drugs during hepatic chemoembolisation. Cardiovasc Intervent Radiol. 2015 (Epub ahead of print).
  • Simons A and Toland S. Closed systems for drug delivery: a necessity, not an option. Brit J Nurs. 2015; 24:S20,S22.
  • Smith ST and Szlaczky MC. Syringe plunger contamination by hazardous drugs: a comparative study. J Oncol Pharm Practice. 2014; 20:381-385.
  • Smith ST and Szlaczky MC. Response to the editor. J Oncol Pharm Practice. 2014; 20:399-400.
  • Spivey S and Connor TH. Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV drug preparation with a closed system. Hosp Pharm. 2003; 38:135-139.
  • Tans B and Willems L. Comparative contamination study with cyclophosphamide, fluorouracil and ifosfamide: standard versus a proprietary closed-handling system. J Oncol Pharm Practice. 2004; 10:217-223.
  • Vandenbroucke J and Robays H. How to protect environment and employees against cytotoxic agents, the UZ Ghent experience. J Oncol Pharm Practice. 2001; 6:146-152.
  • Vyas N, Turner A, Clark JM and Sewell GJ. Evaluation of a closed-system cytotoxic transfer device in a pharmaceutical isolator. J Oncol Pharm Practice. 2014; (Epub ahead of print) DOI: 10.1177/1078155214544993.
  • Vyas N, Yiannakis D, Turner A and Sewell GJ. Occupational exposure to anti-cancer drugs: A review of effects of new technology. J Oncol Pharm Pract. 2014; 20:278-287.
  • Wakui N, Ookubo T, Iwasaki Y, Ito R, Saito K and Nakazawa H. Development of a closed drug preparation method for oral anticancer drugs. J Oncol Pharm Practice. 2013; 19:315-320.
  • Wick C, Slawson MH, Jorgenson JA and Tyler LS. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm. 2003; 60:2314-2320.
  • Yoshida J, Tei G, Mochizuki C, Masu Y, Koda S and Kumagai S. Use of a closed system device to reduce occupational contamination and exposure to antineoplastic drugs in the hospital work environment. Ann Occup Hyg. 2009; 53:153-160.
  • Zock MD, Soefje S and Rickabaugh K. Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activities using two closed-system products. J Oncol Pharm Practice. 2011; 17:49-54.

Work Practice Evaluation

Several approaches have been developed for evaluating work practice techniques for drug preparation and drug administration. These approaches typically rely on a non-toxic substitute for the drug that can be easily visualized by ultra violet light or other means. Some test kits are available for various manufacturers.

  • Friese CR, Himes-Ferris L, Frasier MN, McCullagh MC, Griggs JJ. Structures and processes of care in ambulatory oncology settings and nurse-reported exposure to chemotherapy. BMJ Qual Saf. 2012; 21:753-759.
  • Georgiadi A, Rämme E, Wretman C and Eksborg S. How to create acceptable working conditions for hospital pharmacy staff when preparing cytotoxic drugs. Eur J Hosp Pharm. 2004; 3:40-42.
  • Guillemette A, Langlois H, Voisine M, Merger D, Therrien R, Mercier G, Lebel D and Bussieres JF. Impact and appreciation of two methods aiming at reducing hazardous drug environmental contamination: The centralization of the priming of IV tubing in the pharmacy and use of a closed-system transfer device. J Oncol Pharm Practice. 2014; 20:426-432.
  • Harrison BR, Godefroid RJ and Kavanaugh EA. Quality-assurance testing of staff pharmacists handling cytotoxic agents. Am J Health-Syst Pharm. 1996; 53:402-407.
  • Keat CH, Sooaid NS, Yun CY and Sriraman M. Improving safety-related knowledge, attitude and practices of nurses handling cytotoxic anticancer drugs: Pharmacists’ experience in a general hospital, Malaysia. Asian Pac J Cancer Prev. 2013; 14:69-73.
  • Kopp B, Schierl R and Nowak D. Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health. 2013; 86:47-55.
  • Kromhout H, Hoek F, Uitterhoeve R, Huijbers R, Overmars RF, Anzion R and Vermeulen R. Postulating a dermal pathway for exposure to antineoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Ann Occup Hyg. 2000; 44:551-560.
  • Spivey S and Connor TH. Determining sources of workplace contamination with antineoplastic drugs and comparing conventional IV drug preparation with a closed system. Hosp Pharm. 2003; 38:135-139.
  • Van Raalte J, Rice C and Moss E. Visible-light system for detecting doxorubicin contamination on skin and surfaces. Am J Hosp Pharm. 1990; 47:1067-1074.
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