5 Warning!
Healthcare workers who prepare or administer hazardous drugs or who work in areas where these drugs are used may be exposed to these agents in air or on work surfaces, contaminated clothing, medical equipment, patient excreta, or other sources. Studies have associated workplace exposures to hazardous drugs with health effects such as skin rashes and adverse reproductive events (including infertility, spontaneous abortions or congenital malformations) and possibly leukemia and other cancers. The health risk is influenced by the extent of the exposure and the potency and toxicity of the hazardous drug. Potential health effects can be minimized through sound procedures for handling hazardous drugs, engineering controls and proper use of protective equipment to protect workers to the greatest degree possible. ormally seek input from employees who handle drugs in developing a program for preventing exposure. Prepare a written inventory identifying all hazardous drugs used in the workplace and establish a procedure for regular review and update of the inventory. ake guidance documents, aterial Safety ata Sheets ( S Ss) and other information available to those who handle hazardous drugs or work in an area where hazardous drugs are handled. Provide training to employees on the recognition, evaluation and control of hazardous drugs. nsure that horizontal laminar flow workstations that move the air from the drug towards the worker are never used for the preparation of hazardous drugs. or hazardous drug preparation, provide and maintain ventilated cabinets designed for worker protection. xamples of these include biological safety cabinets ( S s) and containment isolators that are designed to prevent hazardous drugs inside the cabinet from escaping into the surrounding environment. The exhaust from these cabinets should be H P filtered and whenever feasible dditional exhausted to the outdoors (away from air intake locations). equipment, such as closed system drug transfer devices, glove bags and needle less systems will further protect workers from exposures when used properly. stablish and oversee the implementation of appropriate work practices when hazardous drugs, patient wastes and contaminated materials are handled. nsure training in and the availability and use of proper personal protective equipment (PP ) to reduce exposure via inhalation, ingestion, skin absorption, and in ection of hazardous drugs as required based on the results of a risk assessment and the SH PP Standard. PP includes chemotherapy gloves, low lint, low permeability disposable gowns and sleeve covers, and eye and face protection. SH certified respiratory protection is needed when equipment such as biological safety cabinets are not adequate to protect against inhalation exposure. Surgical masks do not provide adequate respiratory protection. Provide syringes and intravenous ( ) sets with uer LokT fittings for preparing and administering hazardous drugs, as well as containers for their disposal. losed system, drug transfer devices and needle less systems should be considered to protect nursing personnel during drug administration. omplete a periodic evaluation of workplace hazardous drugs, equipment, training effectiveness, policies and procedures to reduce exposures to the greatest degree possible. omply with all relevant onservation and ecovery S nvironmental Protection gency esource ct ( S P ) regulations related to the handling, storage and transportation of hazardous waste. a ar r r Participate in standardized training on the hazards of the drugs handled and equipment and procedures used to prevent exposure. eview guidance documents, hazardous drugs handled. e familiar with and be able to recognize sources of exposure to hazardous drugs. S Ss and other information resources for Prepare these agents in a dedicated area where access is restricted to authorized personnel only. Prepare these agents within a ventilated cabinet designed to protect workers and ad acent personnel from exposure and to provide product protection for all drugs that require aseptic handling. se two pairs of powder free, disposable chemotherapy gloves with the outer one covering the gown cuff whenever there is risk of exposure to hazardous drugs. void skin contact by using a disposable gown made of a low lint and low permeability fabric. The gown should have a closed front, long sleeves and elastic or knit closed cuffs and should not be reused. ear a face shield to avoid splash incidents involving eyes, nose, or mouth when adequate engineering controls are not available. ash hands with soap and water immediately before using and after removing personal protective clothing, such as disposable gloves and gowns. se syringes and sets with uer LokT fittings for preparing and administering these agents and place drug contaminated syringes and needles in chemotherapy sharps containers for disposal. hen additional protection is necessary, use closed system, drug transfer devices, glove bags and needle less systems within the ventilated cabinet. Handle hazardous wastes and contaminated materials separately from other trash. econtaminate work areas before and after each activity with hazardous drugs and at the end of each shift. lean up spills immediately while using appropriate safety precautions and personal protective equipment (PP ) unless the spill is large enough to require an environmental services specialist. or additional information, see SH lert Preventing ccupational xposures to ntineoplastic and other Hazardous rugs in Healthcare Settings HHS ( SH) Publication o. xxx . Single copies of the lert are available from the following SH Publications issemination olumbia Pkwy. incinnati, H Telephone SH ( ) ax mail pubstaft cdc.gov r visit the SH eb site www.cdc.gov SH epartment of Health and Human Services enters for isease ontrol and Prevention ational nstitute for ccupational Safety and Health nr W r i n r a i n ia r i i n n ag ni i n a an an r r i rW r r a r r in W r r an a ar r g r a a a a a a rr n r an ar n nia r an i n r a in rag n ai n r an i n i ing an r g r ara i n an in i nr aning ini ra i n n a ina i n ing an Wa i a i a n i n an r i an n ai n i i na n r a i n n r n n i r g ini i n a n i n i ar a ar ni a ar a ar r r a ar r g r g an r ia i n W r ing r g n r g a r n ing a i na r g in a ar r ing n in a i an r a ar Pharmaceutical drugs are used with success to treat illnesses and in uries. The use of pharmaceutical agents is responsible for many of the advances in human medicine over the past century. irtually all pharmaceutical agents have side effects, and, in addition to patients, workers who handle them are at risk of suffering an agent s known or unknown side effects. The term Hospital Pharmacists SHP was first used by the and is used by the SH merican Society of ccupational Safety and Health , . Pharmaceutical dministration ( SH ) in several documents agents are classified as hazardous drugs if studies in animals or humans indicate their potential to cause cancer, developmental or reproductive toxicity, or harm to organs (when it occurs at low doses). any of the agents that are considered hazardous drugs infection . alassi et al. c nnes are used to treat illnesses such as cancer or H and Schilsky rlichman and oore full discussion of criteria used to classify pharmaceutical agents as hazardous drugs, the definition of hazardous drugs, and examples of hazardous drugs are presented in ppendix . hile the potential therapeutic benefits of these drugs outweigh the risks of unwanted side effects for ill patients, these same side effects may pose a hazard to healthcare workers. ccupational exposure can lead to ( ) acute effects, such as skin rashes gan alanis et al. a,b ( ) chronic effects, including c iarmid and adverse reproductive events Selevan et al. alanis et al. . , Peelen et al. Hemminki et al. St cker et al. and ( ) possibly cancer Skov et al. There are guidelines for handling hazardous drugs, but adherence to these guidelines has been reported to be sporadic alanis et al. , ahon et al. ieweg et al. . n addition, measurable levels of some hazardous drugs have been documented in the urine of healthcare workers involved in the preparation or administration of drugs even after safety precautions had been employed oer, et al. al. Sessink, ern inoia et al. nsslin et al. erkhof, et al. , Sessink, Sessink et Sessink, van der ick et al. . nvironmental studies of patient care areas have documented measurable levels of drug contamination even in those facilities thought to be following recommended handling guidelines al. Pethran et al. inoia et al. onnor et ntineoplastic agents are increasingly used in the treatment of non malignant rheumatologic and immunologic diseases et al. osenthal bel aker et al. oody et al. habner , as well as in veterinary medicine for anti cancer chemotherapy Takada , thus expanding the number and types of work lert summarizes the known health environments where these drugs are used. This effects associated with occupational exposure to these agents and reviews elements of existing safe handling recommendations. W Throughout the life cycle of a drug from manufacture to transport and distribution, to use in actual healthcare or home care settings, to waste disposal there are a number of drug handling operations that have the potential for worker exposure. The workers who have the potential to be exposed to hazardous drugs include shipping and receiving personnel pharmacists and pharmacy technicians nursing personnel physicians operating room personnel environmental services personnel and personnel involved in veterinary practices where hazardous drugs are used. This lert addresses all drug handling workers including veterinary care workers, but not those workers in research and development and the drug manufacturing sector. lthough not all workers in these categories handle hazardous drugs, the number of workers who may be exposed to hazardous drugs exceeds . million . .S. ensus ureau S , HS n ia r xposure to hazardous drugs may occur to clinical and non clinical workers in the following settings uring reconstitution of powdered or lyophilized drugs and further dilution of either the reconstituted powder or concentrated liquid forms of hazardous drugs. hen aerosols are generated by expelling air from syringes filled with hazardous drugs or during the administration of drugs by intramuscular, subcutaneous or intravenous routes. hen dust is generated through counting out individual uncoated oral doses and tablets from multi dose bottles or unit dosing uncoated tablets in a unit dose machine, presenting a possible inhalation hazard. hen crushing tablets to make oral liquid doses thus presenting potential inhalation and dermal exposure Harrison and Schultz . orr and lberts Shahsavarani et al. hen compounding potent powders into custom dosage capsules. hen measurable levels of drugs are present on drug vial exteriors, work surfaces, floors, and final drug products (bottles, bags, cassettes, and syringes) and when airborne droplets of the drug are generated during reconstitution c evitt et al. Sessink, van der Sessink, erkhof, et al. . nzion, et al. inoia et al. Sessink, oer, et al. onnor et al. , Schmaus et al. hen aerosols are generated during the administration of drugs, either by direct push or by f priming the infusion. set with drug containing solution at the patient bedside. ( t is recommended that this procedure be done in the pharmacy.) hen handling body fluids, clothing, dressings, linens and other materials contaminated with body fluids by hospital or home health personnel working with patients treated with hazardous drugs . Through handling of contaminated waste generated at all steps of the preparation and administration process. ass and usgrave romhout et al. hen specialized procedures (intraoperative intraperitoneal chemotherapy) are performed in the operating room for some patients . hen handling unused hazardous drug waste, hazardous drug contaminated waste, decontaminating and cleaning drug preparation or clinical areas, and transporting infectious, chemical or hazardous waste containers. hen removing and disposing of PP drugs or waste. used during the handling of hazardous hite et al. Stuart et al. r xposures occur via inhalation, skin absorption, ingestion, and in ection. nhalation and skin exposure are the most likely, while unintentional ingestion from hand to mouth contact and unintentional in ection through a needlestick or sharps in ury are also possible . uvall and aumann orr lack and Presson Schreiber et al. Several studies have attempted to measure concentrations of airborne antineoplastic drugs in healthcare settings Pyy et al. undgren leinberg and c evitt et al. Stuart et al. uinn eal et al. Sessink, nzion, et al. arson et al. c iarmid et al. ygren and . n most iffmeyer et al. cases, the percentage of samples demonstrating the presence of drug particulate was low and the concentration of the drugs, when present, was quite low. These low airborne concentrations may be attributed to the inefficiency of sampling and analytical techniques employed in the past arson et al. . oth particulate and gaseous phases of one iffmeyer et antineoplastic drug, cyclophosphamide, have been reported in two studies al. arson et al. . Since the early s, studies have examined environmental contamination of drug .S. and several other c evitt et al. preparation and administration areas in healthcare facilities in the countries ,Sessink, Pethran et al. onnor et al. iffmeyer et al. nzion et al. , Sessink, Scheefhals, et al. ubino et al. andenbroucke et al. ick et al. . inoia et al. icoli et al. Schmaus et al. Sessink and os onnor et al. sing wipe samples, most studies measured detectable levels of one to five drugs in various locations such as surfaces of S s floors counter tops storage areas tables and chairs in patient ll of the treatment areas and locations ad acent to where the drugs were handled. studies reported some level of contamination with at least one drug and several reported contamination with all the drugs for which assays were performed. Such widespread contamination of work surfaces makes highly probable the potential for dermal contact in both pharmacy and patient areas. i n rW r r r There is evidence that workers are being exposed to hazardous drugs and that they are experiencing serious health consequences despite current work practice guidelines. Protection from exposure to hazardous drugs depends on safety programs established by the employer and adhered to by the employees. actors that affect exposure include drug handling circumstances (preparation, administration, or disposal) amount of drug prepared frequency and duration of handling the drugs potential for absorption and or the use of ventilated cabinets personal protective equipment (PP ) and work practices. The likelihood of experiencing any of the adverse effects associated with hazardous drugs increases as the degree and frequency of exposure increases and when proper work practices are not implemented. orkers exposures have been assessed by studies on biological markers of exposure. o single biological marker has been found to be a good indicator of exposure to hazardous drugs or a good predictor of subsequent adverse health effects onnor . Sessink and os noted that of aker and studies detected cyclophosphamide in the urine of healthcare workers tested, indicating continued exposure despite safety precautions. entilated abinet type of engineering control designed for purposes of worker protection. xamples include biological safety cabinets and isolators designed to prevent hazardous drugs inside the cabinet from escaping into the surrounding environment. See lossary of Terms and bbreviations ( ppendix ) for additional descriptions. Harrison reported that six different drugs (cyclophosphamide, methotrexate, ifosfamide, epirubicin and cisplatin carboplatin) were reported in the urine of healthcare workers in of investigations. Two recent studies have documented antineoplastic ick et al. drugs in the urine of pharmacy and nursing personnel Pethran et al. . Pethran and coworkers collected urine samples in three year period. erman hospitals over a yclophosphamide, ifosfamide, doxorubicin, epirubicin and platinum (from cisplatin or carboplatin), but not daunorubicin or idarubicin, were identified in urine samples from many of the study participants. n investigation conducted in the .S. demonstrated a reduction in both the percentage of urine samples with measurable levels of cyclophosphamide or ifosfamide present and the concentration of the drugs in the urine following use of a closed system device for six months ick et al. . Hazardous drugs have also been documented in the urine of healthcare workers not handling the drugs but potentially exposed via fugitive aerosols or secondary contamination of work surfaces, clothing or drug containers Sessink, van der erkhof, et al. ader et al. Pethran et al. . i n r a in W r r an a ar r g y the s, the carcinogenicity of several antineoplastic drugs in animals was well eisberger Schmahl and Habs . ikewise, established Shimkin et al. a number of researchers during this period linked the therapeutic use of alkylating agents in humans to subsequent leukemia and other cancers Harris , . any in healthcare began to question whether occupational exposure to these agents was hazardous g onner ohansson . ag ni i number of studies indicate that antineoplastic drugs may cause increased genotoxic effects in pharmacists and nurses exposed in the workplace et al et al. . guyen et al. nde er et al. Sessink, ern , et al. ogers and mmett orppa et al. urgaz et al. alck et al. estricher et al. ikula et al. nderson uchs c iarmid et al. . Technical confounders and a lack of accurate sampling of exposed workers urine or blood have been described as explanations for several other studies with negative genotoxic associations Sorsa et al. c iarmid et al. . onsidering all the data, the weight of the evidence in occupationally exposed cohorts demonstrates an association between exposures to hazardous drugs and increases in various measures of genotoxicity Sorsa and aker and Harrison onnor . os and Sessink Hewitt nderson os Sessink and n a an recent review of r i investigations described the association between exposure to antineoplastic agents and adverse reproductive effects and reported nine studies showed some positive association Harrison . The ma or reproductive effects found in these St cker et al. , congenital , low birth alanis et. al. studies were increased fetal loss Selevan et al. malformations depending on the length of exposure Hemminki et al. weight and congenital abnormalities Peelen et al. . , and infertility an r Several reports have addressed cancer occurrence related to exposures of healthcare workers to anticancer drugs. significantly increased risk of leukemia has been reported to Skov et among oncology nurses identified in the anish cancer registry for al. . The same group Skov et al. found an increased, but not significant, risk of leukemia in physicians employed for at least six months in a department where patients were treated with antineoplastic agents. The following case reports illustrate the range of health effects exhibited after exposure to antineoplastic drugs. These case reports are summarized ournal articles. a female oncology nurse was exposed to a solution of carmustine when the complete tubing system fell out of an infusion bottle of carmustine and all of the solution poured down her right arm and leg and onto the floor c iarmid and gan . lthough she wore gloves, her right forearm was unprotected and the solution penetrated her clothing and stockings. eeling no sensation on the affected skin areas, she immediately washed her arm and leg with soap and water, but did not change her clothing. few hours later, while at work, she began to experience minor abdominal distress and profuse belching, followed by intermittent episodes of non bloody diarrhea with cramping abdominal pain. Profuse vomiting occurred, after which she felt better. She went to the emergency room where her vital signs and physical examination were normal, no specific therapy was prescribed. She felt better the following day. armustine is known to cause gastric upset, and the authors attributed her gastrointestinal distress to systemic absorption of carmustine. a evin et al. described the case of a year old pharmacist who presented with papillary transitional two episodes of painless hematuria and was found to have a grade cell carcinoma. History revealed that twelve years prior to diagnosis she worked full time for months in a hospital intravenous preparation area where she routinely prepared cytotoxic agents, including cyclophosphamide, fluorouracil, methotrexate, doxorubicin, and cisplatin. She used a horizontal laminar flow hood that directed the airflow toward her. Since she was a non smoker and had no other known occupational or environmental risk factors, her cancer was attributed to her work exposure to hazardous antineoplastic drugs, although a cause and effect relationship has not been established in the literature. a alusiak et al. reported a case of occupational asthma due to mitoxantrone. years suffered from uring the third year old nurse who had worked on an oncology ward for rhinorrhea, dyspnea and cough attacks hours after beginning work. year, she developed dyspnea while away from work. The total g was low and specific g antibodies to common agents and skin prick tests to common allergens, including latex, were all negative. The patient was sub ected to a number of single blind bronchial challenge tests with antineoplastic drugs and monitored by spirometry and peak expiratory flow measurements. expiratory volume at and itoxantrone produced and falls in forced hours, respectively. The challenge with mitroxantrone was and repeated one week later and bronchoalvelor lavage fluid was taken before and at hours after provocation. Significant increases in lymphocytes and neutorophils were observed at hours. There was also an eosinophil influx and a two fold increase in the ased on the clinical findings, the authors concluded that the permeability index. evidence was consistent with mitroxantrone induced allergic asthma. a evekordes et al. reported on the effects of a malfunctioning S resulting in possible exposure of nursing personnel to a number of antineoplastic drugs that were prepared in the S . lood samples from nurses were analyzed for genotoxic S . t two s) and t nine biomarkers two and nine months following replacement of the faulty months after replacement of the S , both sister chromatid exchanges (S micronuclei were significantly elevated as compared to a matched control group. months, the micronuclei levels were similar to the two month controls. S s were not determined at nine months. The authors concluded that the elevation in the biomarkers had resulted from the malfunctioning of the S resulting in worker exposure to the antineoplastic drugs. They also concluded that the subsequent replacement with a new S contributed to the lowering of the effect seen with the micronucleus test at nine months. a year old patient care assistant working on the oncology floor developed a pruritic, disseminated rash approximately toilet usnetz and ondon minutes after emptying a commode of urine into a . She denied any direct contact with the urine, wore a protective gown and nitrile gloves, and followed hospital policy for the disposal of materials contaminated with antineoplastics. The rash subsided after one to two days. Three weeks later, a similar reaction occurred approximately one hour after performing the same procedure. pon investigation, it was found that both hospital patients had been recently treated with vincristine and doxorubicin. The employee had no other signs or symptoms present, no changes in lifestyle and no history of allergies or recent infections. She was treated with diphenhydramine, intramuscular and oral corticosteroids and became asymptomatic. lthough the cause could not be definitely confirmed, both vincristine and doxorubicin and their metabolites have been associated with allergic reactions when given to patients. The aerosolization of the drug present in the urine may have provided enough exposure for symptoms to develop. urrent ccupational Safety and Health dministration ( SH ) standards and guidelines that address hazardous drugs include the . , the See in references. , . , and the SH Technical SH anual . uidelines, ain elements of the guidelines include ategorization of drugs as hazardous Hazardous drugs as occupational risks ork area Prevention of employee exposure edical surveillance Hazard communication Training and information dissemination ecordkeeping dditional guidelines that address hazardous drugs or the equipment in which they are manipulated include ational Sanitation oundation ( S ) and ( S) S nn rbor, lass merican ational Standards nstitute S S S s ( aminar low) iosafety abinetry , addresses classification and certification of lass S s and provides a definition for lass Technical eport o. , , a supplemental publication to the P ournal of Pharmaceutical Science and Technology , provides definitions, design, and operation and testing guidance for types of isolators used in the healthcare product manufacturing industry , S nd dition, from the merican lovebox Society , provides guidance on the design, testing, use, and decommissioning of glovebox containment systems H selection, installation, testing and use of S s from the nstitutes of Health H ational , provides guidance on the , which includes recommendations for the safe preparation and administration of cytotoxic drugs The merican Society of Health System Pharmacists ( SHP), , which is an informed discussion of the dangers and safe handling procedures for hazardous drugs and The , published by the ncology ursing Society rown et al. provides complete guidelines for the administration of antineoplastic drugs including safe handling guidelines. , published by the Polovich ncology ursing Society includes proper handling guidelines for hazardous drugs. , nited States . nvironmental Protection gency P Parts ecember, . urrently, there are no SH ecommended s) or merican xposure onference of imits ( s), SH Permissible xposure imits (P Hygienists ( T . and an overnment ndustrial n H H) Threshold imit alues (T SH P s ) for hazardous drugs. H exist for soluble platinum salts . However, these are not relevant for the platinum containing antineoplastic ,a and a T for inorganic arsenic compounds, but not H SH drugs. There are also a P for the antineoplastic drug, arsenic trioxide . . Some pharmaceutical manufacturers develop risk based occupational s) to be used in their own manufacturing settings, and this S Ss or from the manufacturer Sargent and Sargent et al . exposure limits ( information may be available on some irk aumann and Sargent n evaluation of the workplace to assess the hazard is recommended prior to anyone working with hazardous drugs. This evaluation should include an assessment of the total working environment, equipment (i.e. ventilated cabinets, closed system drug transfer devices, glovebags, needle less systems and PP ) and the physical layout as well as the type of drugs being handled, the volume, frequency and form (tablet coated versus uncoated, powder versus liquid), maintenance of equipment, decontamination and cleaning and handling of waste. This evaluation should identify all hazards and reflect the range of potential exposure during work activity. t should also include potential exposures to other agents, such as blood borne pathogens and chemicals used to deactivate hazardous drugs or clean surfaces potentially contaminated with them. t should address routine operations, spill response, waste disposal segregation and containment. The health and safety staff or an internal committee should regularly review the current inventory of hazardous drugs, equipment and practices with input from affected employees. egular training reviews should be conducted with all potentially n going input from exposed workers in workplaces where hazardous drugs are used. employees and other potentially exposed workers should be sought regarding the quality and effectiveness of the prevention program. ased upon employee input, management should provide the safest equipment and conditions to reduce healthcare worker exposure to the greatest degree possible. This is the only prudent public health approach as safe levels of occupational exposure for these agents have not been conclusively determined. written workplace safe handling program should be implemented and reviewed annually, based on the workplace evaluation of the area. ork policies and procedures specific to the handling of hazardous drugs should be established. They should include delineation of hazardous materials, labeling, storage, personnel issues (such as pregnancy) and spill control, as well as detailed procedures for preparation, administration, and disposal. n addition, workplace procedures should be developed for the use and maintenance of all equipment that functions to reduce exposure (ventilated cabinets, closed system drug transfer devices, needle less systems, and PP ). ork practices relate not only to drug manipulation techniques but also to general hygiene practices, such as no eating or drinking in the drug handling areas (either pharmacy or clinic). eneral and specific safety training should be provided for handling hazardous drugs, all equipment, PP , spills, and cleanup. Training should include information about location and proper use of spill kits, that should be available in the immediate vicinity of potential sources of unintentional exposure. Training must conform to the requirements of the other relevant SH SH . and requirements. Procedures should also be established for cleaning and decontamination of the work areas and for proper waste handling and disposal of all contaminated materials, including patient waste. nia a in hen mixing, preparing or otherwise manipulating hazardous drugs, including counting or crushing of tablets, compounding powders, or pouring of liquid drugs, these tasks should be conducted within a ventilated cabinet designed specifically to prevent hazardous drugs from being released into the surrounding environment. SH recognizes that aseptic technique is an important requirement for many applications regarding hazardous drugs in order to protect then from possible contamination. These aseptic requirements are generally regulated by individual state boards of pharmacy Thompson . hile the need for asepsis is critical for many operations, this need hen asepsis is required or should not require the sacrifice of worker safety and health. is the recommended work practice, the use of ventilated cabinets designed for both hazardous drug containment and aseptic processing is recommended. The selection of ventilated cabinets intended to control exposures to hazardous drugs will depend upon the need for aseptic processing. hen asepsis is not required, a lass S or an isolator intended for containment applications ( ontainment solator ) may be sufficient. include and lass lass S hen aseptic technique is required, the recommended ventilated cabinets (Type preferred, Type allowed under certain conditions) septic s as well as isolators intended for asepsis and containment ( S S P . ontainment solators ) egardless of type, each ventilated cabinet should be equipped with a continuous monitoring device to allow confirmation of adequate airflow prior to each use. The exhaust from these controls should be H P (High fficiency Particulate ir) filtered and preferably exhausted to the outside. The outside exhaust should be installed to avoid re-entrainment by the building envelope or HVAC systems. Fan placement should be downstream of the H P filter so that contaminated ducts are maintained under negative pressure. ventilated cabinet with air recirculation, either within the cabinet or to the room environment, should only be used if the hazardous drug(s) in use will not volatilize during process manipulation or after capture by the H P filter. nformation on volatilization should be based on information from the drug manufacturer (possibly in the S S) or from air sampling data. dditional information regarding placement of the cabinet, exhaust system, and stack design may be found in S S and should generally be incorporated dditional engineering or regardless of which type of ventilated cabinet is selected. process controls such as needle less systems, glove bags and closed system drug transfer devices are not a substitution for ventilated cabinets although they may provide further benefit in reducing the exposure potential during preparation and administration of hazardous drugs. entilated cabinets require both routine and unscheduled maintenance by building facility personnel or outside contractors. ll maintenance activities performed on ventilated cabinets and exhaust systems associated with hazardous drug procedures should be reviewed, in advance, by a health and safety representative familiar with the potential exposures and their associated hazards. written safety plan should be developed for all routine maintenance activities performed on equipment potentially contaminated with hazardous drugs. ndividuals performing the maintenance operations should be familiar with the applicable safety plans, warned of the potential hazards, and trained on the appropriate work techniques and PP necessary to minimize exposure. nder most circumstances, all hazardous drugs and chemicals should be removed and the ventilated cabinet decontaminated prior to initiating the maintenance activity. ccupants in the affected areas should be warned immediately before the maintenance activity begins and warning signs placed on all equipment which may be affected. lock out tag out procedures should be strictly followed. ll applicable quipment parts, removed for replacement or repair, should be decontaminated and bagged prior to their departure from the facility. sed filtration media should be sealed in plastic immediately upon removal and tagged for disposal as chemotherapy waste or as otherwise directed by the environmental health and safety office or applicable regulation. i ing an rag ontrol of exposure should begin at the point where the drugs enter the facility. The most significant risk for exposure during distribution and transport is from spills, resulting from damaged containers. PP is generally not required when packaging is intact during routine activities. However, workers should be prepared for the possibility of spills during handling of containers. n the outside of containers, medical products should have labeling that is understandable to all levels of personnel who will be separating hazardous drugs from non hazardous. wear chemotherapy gloves ny person opening a container to unpack the drugs should ST , protective clothing and eye protection because there is a possibility of spreading contamination if damaged containers are encountered. hemotherapy gloves should also be worn when transporting the vial or syringe to the work area due to possible contamination. SHP and other chemical safety standards recommend storing hazardous drugs separately from other drugs. Hazardous drugs should also be stored and transported in closed containers that minimize the risk of breakage. The storage area should have sufficient general exhaust ventilation to dilute and remove any airborne contaminants. epending upon the physical nature and quantity of the stored drugs, consideration should be given to installing a dedicated emergency exhaust fan sufficient in size to quickly purge (to the outdoors) any airborne contaminants within the storage room and to prevent airborne contamination in ad acent areas in the event of a spill. r g r ara i n an ini ra i n s part of the hazard assessment (described above), the entire process from drug preparation through drug administration should be evaluated and reviewed for possible unintentional releases of the drug into the work environment. The possibility of os et al. avier et al. contamination on the outside of containers should always be considered Hepp and entschew . elporte et al. ygren et al. ason et al. imiting access to an area designed for drug preparation protects s a matter of practice, worker exposures are more persons not involved in that process. effectively controlled when the tasks associated with the preparation and administration of hazardous drugs are coordinated. uring the preparation of hazardous drugs, a ventilated cabinet (as identified in the entilated abinet section of this document) should be used to reduce the potential for s may be found in occupational exposure. Performance test methods and criteria for S H, . here a class S is used, it should be properly installed, maintained and routinely cleaned. ts performance should be field certified upon installation, following relocation, after maintenance repairs to internal components, after H P S S SH filter replacement and every six months thereafter . current field certification label should be S S . ther types of prominently displayed on the ventilated cabinet ventilated cabinet should be treated similarly as to care and frequency of performance verification tests. Selecting the appropriate performance and test methods for isolators will depend upon the type (containment only or aseptic containment), the operating pressure (positive or negative and designed magnitude), and the toxicity of the hazardous drug being used. t a minimum, isolators should undergo a leak test and containment integrity test such as those described in H P in S uidelines for loveboxes S . Those isolators relying upon filter leak test described filtration for containment should also undergo the H P S . dditional tests may be required by local and or national n addition to appropriate installation, urisdictions to verify aseptic conditions. maintenance, and operation of the ventilated cabinets, the safe use of any control is dependent upon proper work practices. hile certification or performance testing assures the proper operation of the cabinet, it does not assure worker protection. Proper technique and use of equipment should also be practiced. ll staff using ventilated cabinets must nitial be well trained in the work practices established for their particular equipment. and periodic assessments of technique should be included in the safety program Harrison et al. . The technique used during drug administration should also be verified. PP , including double gloves and protective gowns, should be worn during drug reconstitution and admixture. loves should be specified as ST hemotherapy loves and or from the manufacturer. such information should be available on the box hile a number of glove materials are suitable for protecting against exposure to antineoplastic drugs onnor Singleton and onnor lein et al. , consideration must be given to the possibility of individuals who are sensitive to latex products SH . or those hazardous drugs that are not chemotherapy drugs or for which no information is available, a chemotherapy glove should be considered for use. ouble gloving is recommended for all activities involving hazardous drugs and the onnor rown et al. . outer glove should extend over the cuff of the gown loves should be inspected for physical defects before use. Hands should be washed with soap and water before donning protective gloves and immediately following removal. loves should be changed every minutes or when torn, punctured or contaminated and SHP rown et discarded immediately in a yellow chemotherapy waste container al. . Protective gowns should be disposable, low lint, closed in the front, have tight fitting cuffs at the wrist and have low permeability to the agents being handled. Protective gowns must be disposed of after each use. isposable sleeve covers can be used to effectively protect the wrist area by removing the covers after the task is completed. Polypropylene based gown materials provide inadequate protection against many of the commonly used antineoplastic drugs. Polyethylene coated materials provide better protection onnor Harrison and loos . ollowing completion of drug preparation, the final product should be sealed in a plastic bag or other sealable container for transport out of the ventilated cabinet and to other areas. uter gloves and sleeve covers (if used) should be removed and bagged for ll waste containers in the ventilated cabinet orkers involved in disposal inside the ventilated cabinet. should be sealed and wiped prior to their removal from the cabinet. associated activities including opening drug packaging, handling vials or finished product, labeling hazardous drug containers or disposing of waste should wear protective gloves and gowns. Hands should be washed with soap and water immediately following removal of gloves. hile ventilated cabinets should be used for the preparation of hazardous drugs, other devices (closed system transfer devices, glovebags, needle less systems) may offer additional protection benefits for both the preparation and administration of these compounds. Transfers from primary packaging such as vials to dosing equipment (i.e. infusion bags, bottles or pumps) should be carried out using closed systems whenever possible. evices that contain the product within a closed system during drug transfers limit the potential for aerosol generation, as well as exposure to sharps. decrease in drug contaminants present within a transfer device was used. Sessink et al. et al. ygren et al. lass vidence has documented a S when a closed system onnor . However, a andenbroucke and obays ick et al. Spivey and onnor closed system transfer device is not an acceptable substitute for a ventilated cabinet and should only be used in con unction with a ventilated cabinet. egardless of whether a closed system is used, appropriate PP and work practices should always be applied. Safe drug administration includes the use of protective medical devices such as needle less systems, closed systems, and techniques like priming of tubing by pharmacy personnel in the ventilated cabinet or priming in line with non drug solutions. PP , including double gloves, goggles, and protective gowns, should be worn for all activities associated with drug administration opening outer bag, assembly of delivery system, actual patient delivery and removal, and disposal of all equipment used in administration. uter gloves and gowns should be removed and bagged for disposal in the yellow chemotherapy waste container at the site of administration. The chemotherapy waste should be double bagged before removal of the inner gloves. Hands should be washed with soap and water prior to leaving the site of administration. dministration sets should be attached to the drug to the bag. Priming of bag and primed prior to the addition of tubing and syringes should be done by pharmacy personnel in the ventilated cabinet and never in the patient s room. Tubing should never be removed from an bag containing a hazardous drug. Tubing should not be disconnected at other points in the system until the tubing has been thoroughly flushed. hen possible, the bag and tubing should be removed intact. isposable items should be placed directly in a yellow chemotherapy waste container and lids to those containers should be closed. ouble bagging should be considered for all contaminated equipment. in aning n a ina i n ing an Wa i a ork should be done in areas that are sufficiently ventilated to prevent build up of airborne drug concentrations. Protocols should specify that unventilated areas such as storage closets not be used for drug storage or any tasks involving hazardous drugs. ork surfaces should be cleaned according to a cleaning protocol, which includes an appropriate deactivation (if available) and cleaning agent before and after each activity and at the end of the workday. Periodic cleaning routines should be established for all work surfaces and equipment that may become contaminated, including administration carts and trays. should be worn. t a minimum, safety glasses with side shields and protective gloves ace shields should be worn if splashing or spraying is expected. S S, to glove selection loves should be chemically Protective gloves should be selected by referring to the guidelines, or by conferring with the glove manufacturer. resistant to the deactivation or cleaning agent and double gloving is recommended. Personnel handling patient linens and excreta from patients who have received hazardous drugs within the last hours, and in some cases up to seven days ass and usgrave should be provided with and wear two pairs of appropriate gloves, and a disposable gown, to be discarded after each use or whenever contaminated. ace shields should be worn if splashing is possible. The outer gloves and gown should be removed by turning them inside out and placing them into the yellow chemotherapy waste container followed by removal of the inner gloves. Hands should be washed with soap and water after removal of gloves. The preparation and administration of hazardous drugs generates various types of waste, including partially filled vials undispensed products unused gloves gowns underpads and materials from spill cleanups. s needles and syringes nder S P , hazardous waste is a specific category of wastes that must be managed following a strict set of regulatory requirements developed in , included only about . The list of hazardous waste, pharmaceuticals, eight of which were antineoplastic drugs. ecent research has provided evidence that a number of drug formulations exhibit hazardous waste characteristics Smith SHP . SH and recommend hazardous drug waste should be disposed of similar to bags or drug vials that listed hazardous waste. This includes containers such as contain more than trace amounts of hazardous drugs and are not contaminated by blood or other potentially infectious waste. aste, such as needles, empty vials and syringes, gloves, gowns, and tubing that contain trace amounts of hazardous drugs, should be placed in separate containers (traditionally yellow chemotherapy waste containers). Soft trace contaminated items may be placed in chemotherapy bags however, sharps such as needles, syringes and empty vials should be placed in chemotherapy waste containers designed to protect workers from in uries. rug contaminated sharps should not be included in red sharps containers that are used for infectious wastes since these are often autoclaved or microwaved. Trace chemotherapy and other hazardous drugs can be disposed of by a regulated medical waste company through incineration SHP SH Smith . These recommendations are consistent with current knowledge of the toxicity of antineoplastic and other hazardous drugs, as defined in this (i.e., greater than lert, that suggest bulk hazardous drugs be handled similarly to of the initial volume) not listed under hazardous waste and disposed of in a permitted hazardous waste incinerator. Several authors have addressed the risk of potential respiratory exposure from volatile or micro aerosolized drug onnor et al iffmeyer et al arson et al . ssuring containment of chemotherapy related waste in the proper disposal container addresses this concern. i nr Spills should be managed according to workplace hazardous drug spill policy and procedures. The size of the spill might determine both who is authorized to conduct the cleanup and decontamination and how that cleanup is managed. henever possible, cleanup of large spills should be handled by individuals who are trained in handling hazardous materials . . Spill kits and other cleanup materials should be located in the immediate vicinity of a potential, unintentional exposure. However, SH requires that persons who wear respirators such as those contained in some spill kits follow a complete respiratory protection program including fit testing . . The written program should address the protective equipment required for differing amounts spilled, the possible spreading of material, restricted access to hazardous drug spills, and signs to be posted. ll spill cleanup materials should be S P disposed of in a hazardous chemical waste container in accordance with regulations regarding hazardous waste, not in a chemotherapy waste or bio