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ASHP REPORTS Handling hazardous drugs
ASHP Guidelines on Handling Hazardous Drugs

DEVELOPED BY THE ASHP COUNCIL ON PROFESSIONAL AFFAIRS
AND APPROVED BY THE ASHP BOARD OF DIRECTORS ON JANUARY 12, 2006
Am J Health-Syst Pharm. 2006; 63:1172-93
I
n 1990, the American Society of tion from these recommendations NIOSH,4 and individual authors.5-7
Health-System Pharmacists (ASHP) and are current to 2004. The primary goal of this document is
published its revised technical as- to provide recommendations for the
sistance bulletin (TAB) on handling Purpose safe handling of hazardous drugs.
cytotoxic and hazardous drugs.1 The The purpose of these guidelines is These guidelines represent the
information and recommendations to (1) update the reader on new and recommendations of many groups
contained in that document were continuing concerns for health care and individuals who have worked
current to June 1988. Continuing re- workers handling hazardous drugs tirelessly over decades to reduce the
ports of workplace contamination and (2) provide information on rec- potential harmful effects of hazard-
and concerns for health care worker ommendations, including those re- ous drugs on health care workers.
safety prompted the Occupational garding equipment, that have been de- The research available to date, as well
Safety and Health Administration veloped since the publication of the as the opinions of thought leaders in
(OSHA) to issue new guidelines on previous TAB. Because studies have this area, is reflected in the guide-
controlling occupational exposure to shown that contamination occurs in lines. Where possible, recommenda-
hazardous drugs in 1995.2,3 In 2004, many settings, these guidelines should tions are evidence based. In the ab-
the National Institute for Occupa- be implemented wherever hazardous sence of published data, professional
tional Safety and Health (NIOSH) is- drugs are received, stored, prepared, judgment, experience, and common
sued the “NIOSH Alert: Preventing administered, or disposed.2-7 sense have been used.
Occupational Exposure to Antineo- Comprehensive reviews of the lit-
plastic and Other Hazardous Drugs erature covering anecdotal and case Background
in Health Care Settings.”4 The follow- reports of surface contamination, Workers may be exposed to a haz-
ing ASHP Guidelines on Handling worker contamination, and risk as- ardous drug at many points during
Hazardous Drugs include informa- sessment are available from OSHA,2,3 its manufacture, transport, distribu-
Luci A. Power, M.S., is gratefully acknowledged for leading the revi- The bibliographic citation for this document is as follows: Ameri-
sion of these guidelines. ASHP acknowledges the following individu- can Society of Health-System Pharmacists. ASHP guidelines on han-
als for their contributions to these guidelines: Thomas H. Connor, dling hazardous drugs. Am J Health-Syst Pharm. 2006; 63:1172-93.
Ph.D., CAPT (ret.) Joseph H. Deffenbaugh Jr., M.P.H., CDR Bruce These guidelines supersede the ASHP technical assistance bulletin
R. Harrison, M.S., BCOP, Dayna McCauley, Pharm.D., BCOP, on handling cytotoxic and hazardous drugs (Am J Hosp Pharm. 1990;
Melissa A. McDiarmid, M.D., M.P.H., Kenneth R. Mead, M.S., PE, 47:1033-49).
and Martha Polovich, M.N., RN, AOCN. ASHP gratefully acknowl- This is article 204-000-06-002-H04 in the ASHP Continuing Edu-
edges the following individuals for reviewing draft versions of these cation System; it qualifies for 2.0 hours (0.2 CEU) of continuing-
guidelines: Linda Bell, M.S.N., RN, Clyde Buchanan, M.S., FASHP, education credit. See page 1192 or http://ce.ashp.org for the learning
Gayle DeBord, Ph.D., G. Scott Earnest, Ph.D., PE, CSP, Karen objectives, test questions, and instructions.
Finkbiner, Pharm.D., David C. Gammon, Larry W. Griffin, Kathleen
M. Gura, Pharm.D., BCNSP, FASHP, Brenda J. Halling, Joseph Hill, Index terms: American Society of Health-System Pharmacists; Anti-
Eric Kastango, M.B.A., FASHP, Patricia C. Kienle, M.P.A., FASHP, neoplastic agents; Contamination; Control, quality; Equipment;
Patricia Kuban, M.B.A., Cynthia L. LaCivita, Pharm.D., Robert Guidelines; Health professions; Toxicity, environmental
Marino, Pharm.D., BCPS, Patrick E. Parker, M.S.P., Tony Powers,
Pharm.D., Kenneth H. Schell, Pharm.D., FASHP, Charlotte A. Copyright © 2006, American Society of Health-System Pharma-
Smith, M.S., HEM, James G. Stevenson, Pharm.D., FASHP, Marc cists, Inc. All rights reserved 1079-2082/06/0602-1172$06.00.
Stranz, Pharm.D., Lance Tillett, M.P.H., Dennis Tribble, Pharm.D., DOI 10.2146/ajhp050529
Sherry Umhoefer, M.B.A., and Darlene Wiegand, M.S.
1172 Am J Health-Syst Pharm—Vol 63 Jun 15, 2006

tion, receipt, storage, preparation, er contamination and excretion in nation transferred to hands may be
and administration, as well as during combination with animal and pa- ingested via the hand-to-mouth
waste handling and equipment tient studies, was based on a conser- route. 48,49 One or more of these
maintenance and repair. All workers vative exposure level. Connor et al.29 routes might be responsible for
involved in these activities have the found greater surface contamination workers’ exposure.
potential for contact with uncon- in a study of U.S. and Canadian clin- Hazard assessment. The risk to
tained drug. ical settings than had been reported health care personnel from handling
Early concerns regarding the safety in European studies conducted by hazardous drugs is the result of a
of workers handling potentially haz- Sessink and colleagues.30-32 Ensslin et combination of the inherent toxicity
ardous drugs focused on antineo- al. 33 reported an almost fivefold of the drugs and the extent to which
plastic drugs when reports of second greater daily average excretion of cy- workers are exposed to the drugs in
cancers in patients treated with these clophosphamide in their study than the course of their daily job activities.
agents were coupled with the discov- that reported by Sessink. These later Both hazard identification (the qual-
ery of mutagenic substances in nurs- findings could add 7–50 additional itative evaluation of the toxicity of a
es who handled these drugs and cancer cases per year per million given drug) and an exposure assess-
cared for treated patients.8,9 Exposure workers to Sessink’s estimate. From ment (the amount of worker contact
to these drugs in the workplace has these and other studies that show with the drug) are required to com-
been associated with acute and short- variations in work practices and en- plete a hazard assessment. As the
term reactions, as well as long-term gineering controls, 34,35 it may be as- hazard assessment is specific to the
effects. Anecdotal and case reports sumed that such variations contrib- safety program and safety equipment
in the literature range from skin- ute to differences in surface and in place at a work site, a formal haz-
related and ocular effects to flu-like worker contamination. ard assessment may not be available
symptoms and headache.4,5,10-17 Two Routes of exposure. Numerous for most practitioners. An alternative
controlled surveys have reported sig- studies showed the presence of haz- is a performance-based, observation-
nificant increases in a number of ardous drugs in the urine of health al approach. Observation of current
symptoms, including sore throat, care workers. 30-34,36-41 Hazardous work practices, equipment, and the
chronic cough, infections, dizziness, drugs enter the body through inhala- physical layout of work areas where
eye irritation, and headaches, among tion, accidental injection, ingestion hazardous drugs are handled at any
nurses, pharmacists, and pharmacy of contaminated foodstuffs or mouth given site will serve as an initial as-
technicians routinely exposed to haz- contact with contaminated hands, sessment of appropriate and inap-
ardous drugs in the workplace.18,19 and dermal absorption. While inha- propriate practices.4
Reproductive studies on health care lation might be suspected as the pri-
workers have shown an increase in mary route of exposure, air sampling Hazardous drugs as sterile
fetal abnormalities, fetal loss, and studies of pharmacy and clinic envi- preparations
fertility impairment resulting from ronments have often demonstrated Many hazardous drugs are de-
occupational exposure to these po- low levels of or no airborne contami- signed for parenteral administration,
tent drugs.20-23 Antineoplastic drugs nants.30-32,40 Recent concerns about requiring aseptic reconstitution or
and immunosuppressants are some the efficacy of the sampling meth- dilution to yield a final sterile prepa-
of the types of drugs included on lists ods42 and the possibility that at least ration. As such, the compounding of
of known or suspected human car- one of the marker drugs may be vola- these products is regulated as pharma-
cinogens by the National Toxicology tile42-45 and thus not captured on the ceutical compounding by the United
Program 24 and the International standard sampling filter leave the States Pharmacopeia (USP), chapter
Agency for Research on Cancer.25 Al- matter of inhalational exposure un- 797.50 The intent of chapter 797 is to
though the increased incidence of resolved. Surface contamination protect patients from improperly
cancers for occupationally exposed studies do, however, suggest that compounded sterile preparations by
groups has been investigated with dermal contact and absorption may regulating facilities, equipment, and
varying results,26,27 a formal risk as- be a primary route of exposure.31,46 work practices to ensure the sterility
sessment of occupationally exposed While some hazardous drugs are der- of extemporaneously compounded
pharmacy workers by Sessink et al.28 mally absorbed, a 1992 report sterile preparations. Chapter 797 ad-
estimated that cyclophosphamide showed no detectable skin absorp- dresses not only the sterility of a
causes an additional 1.4–10 cases of tion of doxorubicin, daunorubicin, preparation but also the accuracy of its
cancer per million workers each year. vincristine, vinblastine, or mel- composition. Because many hazard-
This estimate, which considered phalan.47 An alternative to dermal ous drugs are very potent, there is little
workplace contamination and work- absorption is that surface contami- margin for error in compounding.
Am J Health-Syst Pharm—Vol 63 Jun 15, 2006 1173

The initial version of chapter 797, ardous chemical as any chemical that Working Group on Hazardous
released in early 2004, provided only is a physical or health hazard.52,53 A Drugs for the 2004 alert.4 These defi-
minimal guidance for the handling health hazard is defined as a chemical nitions are compared in Table 1.
of hazardous drugs, limiting this for which there is statistically signifi- Each facility should create its
issue to a short discussion of chemo- cant evidence, based on at least one own list of hazardous drugs based on
toxic agents in the document’s sec- study conducted in accordance with specific criteria. Appendix A of
tion on aseptic technique. The chap- established scientific principles, that the NIOSH alert contains related
ter referred to standards established acute or chronic health effects may guidance and a sample list.4 When
by the International Organization for occur in exposed employees. The drugs are purchased for the first
Standardization (ISO)51 that address HCS further notes that the term time, they must be evaluated to de-
the acceptable air quality (as mea- health hazard includes chemicals that termine whether they should be in-
sured by particulate counts) in the are carcinogens, toxic or highly toxic cluded in the facility’s list of hazard-
critical environment but failed to agents, reproductive toxins, irritants, ous drugs. As the use and number of
discuss airflow, air exchanges per corrosives, sensitizers, and agents hazardous drugs increase, so too do
hour, or pressure gradients of the that produce target organ effects. the opportunities for health care
ISO standards for cleanrooms and A 1990 ASHP TAB proposed cri- worker exposure. Investigational
associated environments for com- teria to determine which drugs drugs must be evaluated according to
pounding sterile products. The chap- should be considered hazardous and the information provided to the
ter did not describe the containment handled within an established safety principal investigator. If the infor-
procedures necessary for compound- program.1 OSHA adopted these cri- mation provided is deemed insuffi-
ing sterile hazardous agents, leaving teria in its 1995 guidelines, which cient to make an informed decision,
it to the practitioner to simulta- were posted on its Web site in 1999.2,3 the investigational drug should be
neously comply with the need to The TAB’s definition of hazardous considered hazardous until more in-
maintain a critical environment for drugs was revised by the NIOSH formation is available.
compounded sterile products for
patient safety while ensuring a con-
tained environment for worker safe-
ty. The use of positive-pressure isola- Table 1.
tors for compounding hazardous Comparison of 2004 NIOSH and 1990 ASHP Definitions of Hazardous
drugs or placement of a Class II bio- Drugsa
logical-safety cabinet (BSC) for use NIOSH4 ASHP1
with hazardous drugs in a positive- Carcinogenicity Carcinogenicity in animal models, in the
pressure environment may result in patient population, or both as reported
airborne contamination of adjacent by the International Agency for
Research on Cancer
areas. Engineering assessment of de- Teratogenicity or developmental toxicityb Teratogenicity in animal studies or in
signs of areas where this may occur treated patients
should be done to address concerns Reproductive toxicityb Fertility impairment in animal studies or
in treated patients
of contaminant dissemination. Be- Organ toxicity at low dosesb Evidence of serious organ or other
cause hazardous drugs are also com- toxicity at low doses in animal models
pounded in areas adjacent to patients or treated patients
Genotoxicityc Genotoxicity (i.e., mutagenicity and
and their family members (e.g., in clastogenicity in short-term test
chemotherapy infusion centers), in- systems)
appropriate environmental contain- Structure and toxicity profile of new
drugs that mimic existing drugs
ment puts them, as well as health care determined hazardous by the above
workers, at risk. Because USP review criteria
is a dynamic and ongoing process, aNIOSH = National Institute for Occupational Safety and Health, ASHP = American Society of Health-System
future revisions are likely to address Pharmacists.

bNIOSH’s definition contains the following explanation: “All drugs have toxic side effects, but some exhibit
these concerns. Practitioners are en- toxicity at low doses. The level of toxicity reflects a continuum from relatively nontoxic to production of toxic
couraged to monitor the process and effects in patients at low doses (for example, a few milligrams or less). For example, a daily therapeutic dose of 10
mg/day or a dose of 1 mg/kg/day in laboratory animals that produces serious organ toxicity, developmental
participate when appropriate. toxicity, or reproductive toxicity has been used by the pharmaceutical industry to develop occupational
exposure limits (OELs) of less than 10 micrograms/meter3 after applying appropriate uncertainty factors. OELs in
this range are typically established for potent or toxic drugs in the pharmaceutical industry. Under all
Definition of hazardous drugs circumstances, an evaluation of all available data should be conducted to protect health care workers.”
cNIOSH’s definition contains the following explanation: “In evaluating mutagenicity for potentially hazardous
The federal hazard communica- drugs, responses from multiple test systems are needed before precautions can be required for handling such
tion standard (HCS) defines a haz- agents. The EPA evaluations include the type of cells affected and in vitro versus in vivo testing.”

Recommendations of the packing cartons and onto the respirator, is recommended.56,57 As

Safety program. Policies and pro- package inserts placed around the required by OSHA, a complete respi-
cedures for the safe handling of haz- vial within the carton. Such contami- ratory program, including proper
ardous drugs must be in place for all nation would present an exposure training and fit testing, must be com-
situations in which these drugs are risk to anyone opening drug cartons pleted by all staff required to use res-
used throughout a facility. A com- or handling the vials, including pirators.56 Surgical masks do not pro-
prehensive safety program must be workers receiving open or broken vide adequate protection from the
developed that deals with all aspects shipping cartons or selecting vials to harmful effects of these drugs.
of the safe handling of hazardous be repackaged at a distribution point Labeling and packaging from
drugs. This program must be a (e.g., a worker at the drug wholesaler point of receipt. Drug packages,
collaborative effort, with input from selecting hazardous drugs for ship- bins, shelves, and storage areas for
all affected departments, such as ping containers or a pharmacy work- hazardous drugs must bear distinc-
pharmacy, nursing, medical staff, er dividing a hazardous drug in a tive labels identifying those drugs as
housekeeping, transportation, main- multidose container for repackaging requiring special handling precau-
tenance, employee health, risk man- into single-dose containers). These tions. Segregation of hazardous drug
agement, industrial hygiene, clinical activities may present risks, especial- inventory from other drug inventory
laboratories, and safety. A key ele- ly for workers who too often receive improves control and reduces the
ment of this safety program is the inadequate safety training. House- number of staff members potentially
Material Safety Data Sheet (MSDS) keepers and patient care assistants exposed to the danger. Hazardous
mandated by the HCS.52,53 Employers who handle drug waste and patient drugs should be stored in an area
are required to have an MSDS avail- waste are also at risk and are not al- with sufficient general exhaust venti-
able for all hazardous agents in the ways included in the safe handling lation to dilute and remove any air-
workplace. A comprehensive safety training required by safety programs. borne contaminants. 4 Hazardous
program must include a process for Safety programs must identify and drugs placed in inventory must be
monitoring and updating the MSDS include all workers who may be at protected from potential breakage by
database. When a hazardous drug is risk of exposure. storage in bins that have high fronts
purchased for the first time, an The packaging (cartons, vials, am- and on shelves that have guards to
MSDS must be received from the puls) of hazardous drugs should be prevent accidental falling. The bins
manufacturer or distributor. The properly labeled by the manufacturer must also be appropriately sized to
MSDS should define the appropriate or distributor with a distinctive iden- properly contain all stock. Care
handling precautions, including pro- tifier that notifies personnel receiv- should be taken to separate hazard-
tective equipment, controls, and spill ing them to wear appropriate per- ous drug inventory to reduce poten-
management associated with the sonal protective equipment (PPE) tial drug errors (e.g., pulling a look-
drug. Many MSDSs are available on- during their handling. Sealing these alike vial from an adjacent drug bin).
line through the specific manufac- drugs in plastic bags at the distribu- Because studies have shown that
turer or through safety-information tor level provides an additional level contamination on the drug vial itself
services. of safety for workers who are re- is a consideration,30,54,55 all staff mem-
Drugs that have been identified as quired to unpack cartons. Visual ex- bers must wear double gloves when
requiring safe handling precautions amination of such cartons for out- stocking and inventorying these
should be clearly labeled at all times ward signs of damage or breakage drugs and selecting hazardous drug
during their transport and use. The is an important first step in the re- packages for further handling. All
HCS applies to all workers, including ceiving process. Policies and proce- transport of hazardous drug packag-
those handling hazardous drugs at dures must be in place for handling es must be done in a manner to re-
the manufacturer and distributor damaged cartons or containers of duce environmental contamination
levels. Employers are required to es- hazardous drugs (e.g., returning the in the event of accidental dropping.
tablish controls to ensure worker damaged goods to the distributor us- Hazardous drug packages must be
safety in all aspects of the distribu- ing appropriate containment tech- placed in sealed containers and la-
tion of these drugs. niques). These procedures should in- beled with a unique identifier. Carts
The outside of the vials of many clude the use of PPE, which must be or other transport devices must be
commercial drugs are contaminated supplied by the employer. As there designed with guards to protect
by the time they are received in the may be no ventilation protection in against falling and breakage. All indi-
pharmacy.30,54,55 Although the possi- the area where damaged containers viduals transporting hazardous
bility has not been studied, the con- are handled, the use of complete drugs must have safety training that
tamination may extend to the inside PPE, including an NIOSH-certified includes spill control and have spill

kits immediately accessible. Staff members near the compounding contaminants. Depending on the de-
handling hazardous drugs or clean- area, care must be taken to minimize sign, ventilated cabinets may also be
ing areas where hazardous drugs are environmental contamination and to used to provide the critical environ-
stored or handled must be trained to maximize the effectiveness of clean- ment necessary to compound sterile
recognize the unique identifying la- ing (decontamination) activities. The preparations. When asepsis is not re-
bels used to distinguish these drugs design of such areas must include quired, a Class I BSC or a contain-
and areas. Warning labels and signs surfaces that are readily cleaned and ment isolator may be used to handle
must be clear to non-English readers. decontaminated. Upholstered and hazardous drugs. When sterile haz-
All personnel who work with or carpeted surfaces should be avoided, ardous drugs are being compounded,
around hazardous drugs must be as they are not readily cleaned. Sever- a Class II or III BSC or an isolator
trained to appropriately perform al studies have shown floor contami- intended for aseptic preparation and
their jobs using the established pre- nation and the ineffectiveness of containment is required. 4 Recom-
cautions and required PPE.52 cleaning practices on both floors and mendations for work practices spe-
Environment. Hazardous drugs surfaces.29,30,46 Break rooms and re- cific to BSCs and isolators are dis-
should be compounded in a con- freshment areas for staff, patients, cussed later in these guidelines.
trolled area where access is limited to and others should be located away Class II BSCs. In the early 1980s,
authorized personnel trained in han- from areas of potential contamina- the Class II BSC was determined to
dling requirements. Due to the haz- tion to reduce unnecessary exposure reduce the exposure of pharmacy
ardous nature of these preparations, to staff, visitors, and others. compounding staff to hazardous
a contained environment where air Hazardous drugs may also be ad- preparations, as measured by the
pressure is negative to the surround- ministered in nontraditional loca- mutational response to the Ames test
ing areas or that is protected by an tions, such as the operating room, by urine of exposed subjects. 58,59
airlock or anteroom is preferred. which present challenges to training Studies in the 1990s, using analytical
Positive-pressure environments for and containment. Intracavitary ad- methods significantly more specific
hazardous drug compounding ministration of hazardous drugs and sensitive than the Ames test, in-
should be avoided or augmented (e.g., into the bladder, peritoneal dicated that environmental and
with an appropriately designed ante- cavity, or chest cavity) frequently re- worker contamination occurs in
chamber because of the potential quires equipment for which locking workplace settings despite the use of
spread of airborne contamination connections may not be readily avail- controls recommended in published
from contaminated packaging, poor able or even possible. All staff mem- guidelines, including the use of Class
handling technique, and spills. bers who handle hazardous drugs II BSCs.29-35,37-41,60,61 The exact cause of
Only individuals trained in the should receive safety training that in- contamination has yet to be deter-
administration of hazardous drugs cludes recognition of hazardous mined. Studies have shown that (1)
should do so. During administration, drugs and appropriate spill response. there is contamination on the out-
access to the administration area Hazardous drug spill kits, contain- side of vials received from manufac-
should be limited to patients receiv- ment bags, and disposal containers turers and distributors, 30,54,55 (2)
ing therapy and essential personnel. must be available in all areas where work practices required to maximize
Eating, drinking, applying makeup, hazardous drugs are handled. Tech- the effectiveness of the Class II BSC
and the presence of foodstuffs should niques and ancillary devices that are neglected or not taught,32,46 and
be avoided in patient care areas while minimize the risk of open systems (3) the potential vaporization of
hazardous drugs are administered. should be used when administering hazardous drug solutions may re-
For inpatient therapy, where lengthy hazardous drugs through unusual duce the effectiveness of the high-
administration techniques may be routes or in nontraditional locations. efficiency particulate air (HEPA) fil-
required, hanging or removing haz- Ventilation controls. Ventilation ter in providing containment. 42-45
ardous drugs should be scheduled to or engineering controls are devices Studies of surface contamination have
reduce exposure of family members designed to eliminate or reduce discovered deposits of hazardous
and ancillary staff and to avoid the worker exposure to chemical, biolog- drugs on the floor in front of the Class
potential contamination of dietary ical, radiological, ergonomic, and II BSC, indicating that drug may have
trays and personnel. physical hazards. Ventilated cabinets escaped through the open front of the
Because much of the compound- are a type of ventilation or engineer- BSC onto contaminated gloves or the
ing and administration of hazardous ing control designed for the purpose final product or into the air.29-32
drugs throughout the United States of worker protection.4 These devices Workers must understand that
is done in outpatient or clinic set- minimize worker exposure by con- the Class II BSC does not prevent
tings with patients and their family trolling the emission of airborne the generation of contamination

within the cabinet and that the effec- currently focus on applications in the be less sensitive to drafts and other
tiveness of such cabinets in contain- nuclear industry and not on com- laminar-airflow equipment, includ-
ing hazardous drug contamination pounding hazardous drugs.65 There ing positive-pressure environments.
depends on operators’ use of proper are no standardized definitions or Issues unique to isolators include
technique. criteria for pharmaceutical com- pressure changes when accessing the
Some Class II BSCs recirculate air- pounding applications for this fixed-glove assembly, pressure
flow within the cabinet or exhaust equipment and no performance changes in the main chamber when
contaminated air back into the work standards determined by an inde- accessing the antechamber or pass-
environment through HEPA filters.62 pendent organization to aid the pur- through, positive- versus negative-
The Class II BSC is designed with air chaser in the selection process. pressure isolators used to compound
plenums that are unreachable for NIOSH recommends that only venti- hazardous drugs, and ergonomic
surface decontamination; the ple- lated engineering controls be used considerations associated with a
num under the work tray collects to compound hazardous drugs and fixed-glove assembly. Many isolators
room dirt and debris that mix with that these controls be designed for produce less heat and noise than
hazardous drug residue when the containment.4 NIOSH defines these Class II BSCs.68 The Controlled Envi-
BSC is operational.1 Drafts, supply- controls and details their use and se- ronment Testing Association has de-
air louvers, and other laminar flow lection criteria as well as recommen- veloped an applications guide for
equipment placed near the BSC can dations for airflow, exhaust, and isolators in health care facilities.71
interfere with the containment prop- maintenance. NIOSH further differ- Isolators, like Class II BSCs, do
erties of the inflow air barrier, result- entiates between ventilated engineer- not prevent the generation of con-
ing in contamination of the work en- ing controls used for hazard contain- tamination within the cabinet work-
vironment.63 More information on ment that are intended for use with space, and their effectiveness in con-
the design and use of Class II BSCs is sterile products (aseptic contain- taining contamination depends on
available from the NSF International ment) and those for use with non- proper technique.72 The potential for
(NSF)/American National Standards sterile handling of hazardous drugs.4 the spread of hazardous drug con-
Institute (ANSI) standard 49-04.62 An isolator may be considered a tamination from the pass-through
Recommendations for use of Class II ventilated controlled environment and main chamber of the isolator to
BSCs are listed in Appendix A. that has fixed walls, floor, and ceil- the workroom may be reduced by
Alternatives to Class II BSCs. Alter- ing. For aseptic use, supply air must surface decontamination, but no
natives to the open-front Class II be drawn through a high-efficiency wipe-down procedures have been
BSC include the Class III BSC, glove (minimum HEPA) filter. Exhaust air studied. Surface decontamination
boxes, and isolators. By definition, a must also be high-efficiency filtered may be more readily conducted in
Class III BSC is a totally enclosed, and should be exhausted to the out- isolators than in Class II BSCs. (See
ventilated cabinet of leak-tight con- side of the facility, not to the work- Decontamination, deactivation, and
struction.64 Operations in the cabinet room. Workers access the isolator’s cleaning for more information.)
are conducted through fixed-glove work area, or main chamber, Recirculating isolators depend on
access. The cabinet is maintained un- through gloves, sleeves, and air locks high-efficiency (HEPA or ultra-low
der negative air pressure. Supply air or pass-throughs. Currently available penetrating air [ULPA]) filters.
is drawn into the cabinet through isolators have either unidirectional These filters may not sufficiently
HEPA filters. The exhaust air is or turbulent airflow within the remove volatile hazardous drug con-
treated by double HEPA filtration main chamber. For compounding tamination from the airflow. Isola-
or by HEPA filtration and incinera- sterile preparations, the filtered air tors that discharge air into the work-
tion. The Class III BSC is designed and airflow must achieve an ISO room, even through high-efficiency
for use with highly toxic or infectious class 5 (former FS-209E class 100) filters, present exposure concerns
material. Because of the costs of environment within the isola- similar to those of unvented Class II
purchasing and operating a Class III tor.50,51,66,67 Isolators for sterile com- BSCs if there is a possibility that the
BSC, it is seldom used for extempo- pounding have become increasingly hazardous drugs handled in them
raneous compounding of sterile popular as a way to minimize the may vaporize. Isolators used for
products. challenges of a traditional cleanroom compounding hazardous drugs
Less rigorous equipment with and some of the disadvantages of the should be at negative pressure or use
similar fixed-glove access include Class II BSC.50,68-70 The totally en- a pressurized air lock to the sur-
glove boxes and isolators. Although closed design may reduce the escape rounding areas to improve contain-
standardized definitions and criteria of contamination during the com- ment. Some isolators rely on a low-
exist for glove boxes, these guidelines pounding process. The isolator may particulate environment rather than

laminar-airflow technology to pro- formally studied with the results either material when challenged with
tect the sterility of the preparations. published in peer-reviewed journals. six antineoplastic agents.
Recommendations for use of Class As other products become available, In most glove-testing systems, the
III BSCs and isolators are summa- they should meet the definition of glove material remains static, in con-
rized in Appendix B. closed-system drug-transfer devices trast to the stressing and flexing that
Closed-system drug-transfer devic- established by NIOSH4 and should occur during actual use. In one study
es. Closed-system drug-transfer de- be required to demonstrate their ef- designed to examine glove perme-
vices mechanically prevent the trans- fectiveness in independent studies. ability under static and flexed con-
fer of environmental contaminants Closed-system drug-transfer devices ditions, no significant difference in
into the system and the escape of (or any other ancillary devices) are permeation was reported, except in
drug or vapor out of the system.4 not a substitute for using a ventilated thin latex examination gloves.87 An-
ADD-Vantage and Duplex devices cabinet. other study, however, detected per-
are closed-system drug-transfer de- Personal protective equipment. meation of antineoplastic drugs
vices currently available for inject- Gloves. Gloves are essential for han- through latex gloves during actual
able antibiotics. A similar system that dling hazardous drugs. Gloves must working conditions by using a
may offer increased environmental be worn at all times when handling cotton glove under the latex glove.88
protection for hazardous drugs is a drug packaging, cartons, and vials, The breakthrough time for cyclo-
proprietary, closed-system drug- including while performing invento- phosphamide was only 10 minutes.
transfer device known as PhaSeal. ry control procedures and when The authors speculated that the
This multicomponent system uses a gathering hazardous drugs and sup- cotton glove may have acted as a
double membrane to enclose a spe- plies for compounding a batch or wick, drawing the hazardous drug
cially cut injection cannula as it single dose. During compounding in through the outer glove. Nonethe-
moves into a drug vial, Luer-Lok, or a Class II BSC, gloves and gowns are less, under actual working condi-
infusion-set connector. required to prevent skin surfaces tions, double gloving and wearing
Several studies have shown a re- from coming into contact with these gloves no longer than 30 minutes are
duction in environmental contami- agents. Studies of gloves indicate that prudent practices.
nation with marker hazardous drugs many latex and nonlatex materials Permeability of gloves to hazard-
during both compounding and ad- are effective protection against pene- ous drugs has been shown to be de-
ministration when comparing stan- tration and permeation by most haz- pendent on the drug, glove material
dard techniques for handling hazard- ardous drugs.80-84 Recent concerns and thickness, and exposure time.
ous drugs with the use of PhaSeal.73-78 about latex sensitivity have prompt- Powder-free gloves are preferred be-
It should be noted, however, that ed testing of newer glove materials. cause powder particulates can con-
PhaSeal components cannot be used Gloves made of nitrile or neoprene taminate the sterile processing area
to compound all hazardous drugs. rubber and polyurethane have been and absorb hazardous drug contami-
In 1984, Hoy and Stump79 con- successfully tested using a battery of nants, which may increase the poten-
cluded that a commercial air-venting antineoplastic drugs.82-84 The Ameri- tial for dermal contact. Hands should
device reduced the release of drug can Society for Testing and Materials be thoroughly washed before don-
aerosols during reconstitution of (ASTM) has developed testing stan- ning gloves and after removing them.
drugs packaged in vials. The testing dards for assessing the resistance of Care must be taken when removing
was limited to visual analysis. The medical gloves to permeation by che- gloves in order to prevent the spread-
venting device does not lock onto the motherapy drugs.85 Gloves that meet ing of hazardous drug contaminants.
vial, which allows it to be transferred this standard earn the designation of Several studies have indicated
from one vial to another. This prac- “chemotherapy gloves.” Gloves se- that contamination of the outside
tice creates an opportunity for both lected for use with hazardous drugs of gloves with hazardous drug is
environmental and product contam- should meet this ASTM standard. common after compounding and
ination. Many devices labeled as Connor and Xiang86 studied the that this contamination may be
“chemo adjuncts” are currently effect of isopropyl alcohol on the spread to other surfaces during the
available. Many feature a filtered, permeability of latex and nitrile compounding process.30-33,39 Studies
vented spike to facilitate reconstitut- gloves exposed to antineoplastic have also shown that hazardous drug
ing and removing hazardous drugs agents. During the limited study pe- contamination may lead to dermal
during the compounding process. riod of 30 minutes, they found that absorption by workers not actively
However, none of these devices may the use of isopropyl alcohol during involved in the compounding and ad-
be considered a closed-system drug- cleaning and decontaminating did ministration of hazardous drugs.30,88
transfer device, and none has been not appear to affect the integrity of The use of two pairs of gloves is rec-

ommended when compounding gloves should be considered contam- of gowns for compounding in the
these drugs. In an isolator, one addi- inated, and glove surfaces must never BSC, administration, spill control,
tional pair of gloves must be worn touch the skin or any surface that and waste management to protect
within the fixed-glove assembly.68 may be touched by the unprotected the worker from contamination by
Once compounding has been skin of others. Gloves used to handle fugitive drug generated during the
completed and the final preparation hazardous drugs should be placed in handling process.1-4,89,90 Early recom-
surface decontaminated, the outer a sealable plastic bag for containment mendations for barrier protective
glove should be removed and con- within the BSC or isolator pass- gowns required that they be dispos-
tained inside the BSC. The inner through before disposal as contami- able and made of a lint-free, low-
glove is worn to affix labels and place nated waste. permeability fabric with a closed
the preparation into a sealable con- If an i.v. set is attached to the final front, long sleeves, and tight-fitting
tainment bag for transport. This preparation in the BSC or isolator, elastic or knit cuffs. 1 Washable
must be done within the BSC. In the care must be taken to avoid contami- garments (e.g., laboratory coats,
isolator, the fixed gloves must be sur- nating the tubing with hazardous scrubs, and cloth gowns) absorb flu-
face cleaned before wiping down the drug from the surface of the gloves, ids and provide no barrier against
final preparation, placing the label BSC, or isolator. hazardous drug absorption and per-
onto the preparation, and placing it Class III BSCs and isolators are meation. Studies into the effec-
into the pass-through. The inner equipped with attached gloves or tiveness of disposable gowns in re-
gloves should be worn to complete gauntlets. They should be considered sisting permeation by hazardous
labeling and to place the final prepa- contaminated once the BSC or isola- drugs found variation in the protec-
ration into a transport bag in the tor has been used for compounding tion provided by commercially avail-
pass-through. The inner gloves may hazardous drugs. For compounding able materials. In an evaluation of
then be removed and contained in a sterile preparations, attached gloves polypropylene-based gowns, Connor91
sealable bag within the pass-through. or gauntlets must be routinely found that polypropylene spun-
If the final check is conducted by a sanitized per the manufacturer’s bond nonwoven material alone
second staff member, fresh gloves instructions to prevent microbial and polypropylene–polyethylene
must be donned before handling the contamination. Hazardous drug copolymer spun-bond provided little
completed preparation. contamination from the gloves or protection against permeation by a
During batch compounding, gauntlets may be transferred to the battery of aqueous- and nonaqueous-
gloves should be changed at least ev- surfaces of all items within the cabi- based hazardous drugs. Various con-
ery 30 minutes. Gloves (at least the net. Glove and gauntlet surfaces structions of polypropylene (e.g.,
outer gloves) must be changed when- must be cleaned after compounding spun-bond/melt-blown/spun-bond)
ever it is necessary to exit and re- is complete. All final preparations result in materials that are complete-
enter the BSC. For aseptic protection must be surface decontaminated by ly impermeable or only slightly per-
of sterile preparations, the outer staff, wearing clean gloves to avoid meable to hazardous drugs. Connor91
gloves must be sanitized with an ap- spreading contamination.68 Recom- noted that these coated materials are
propriate disinfectant when reenter- mendations for use of gloves are similar in appearance to several other
ing the BSC. Gloves must also be summarized in Appendix C. nonwoven materials but perform
changed immediately if torn, punc- Gowns. Gowns or coveralls are differently and that workers could
tured, or knowingly contaminated. worn during the compounding of expect to be protected from exposure
When wearing two pairs of gloves in sterile preparations to protect the for up to four hours when using the
the BSC, one pair is worn under the preparation from the worker, to pro- coated gowning materials. Harrison
gown cuff and the second pair placed tect the worker from the preparation, and Kloos92 reported similar findings
over the cuff. When removing the or both. The selection of gowning in a study of six disposable gowning
gloves, the contaminated glove fin- materials depends on the goal of the materials and 15 hazardous drugs.
gers must only touch the outer process. Personal protective gowns Only gowns with polyethylene or vi-
surface of the glove, never the inner are recommended during the han- nyl coatings provided adequate
surface. If the inner glove becomes dling of hazardous drug preparations splash protection and prevented
contaminated, then both pairs of to protect the worker from inadvert- drug permeation. In a subjective as-
gloves must be changed. When re- ent exposure to extraneous drug par- sessment of worker comfort, the
moving any PPE, care must be taken ticles on surfaces or generated during more protective gowns were found to
to avoid introducing hazardous drug the compounding process. be warmer and thus less comfortable.
contamination into the environ- Guidelines for the safe handling of These findings agree with an earlier
ment. Both the inner and outer hazardous drugs recommend the use study that found that the most pro-

tective gowning materials were the protection in the compounding of imize particulate contamination of
most uncomfortable to wear.93 Resis- hazardous drugs must never be worn the critical work zone and the prepa-
tance to the use of gowns, especially outside the immediate preparation ration.50 With the potential for haz-
by nurses during administration of area. Gowns worn during adminis- ardous drug contamination on the
hazardous drugs, has been report- tration should be changed when floor in the compounding and ad-
ed.94 The lack of comfort could cause leaving the patient care area and im- ministration areas, shoe coverings
resistance to behavioral change. mediately if contaminated. Gowns are recommended as contamination-
Researchers have looked at gown should be removed carefully and control mechanisms. Shoe coverings
contamination with fluorescent properly disposed of as contaminat- must be removed with gloved hands
scans, high-performance liquid chro- ed waste to avoid becoming a source when leaving the compounding area.
matography, and tandem mass spec- of contamination to other staff and Gloves should be worn and care
trometry.39,95 In one study, research- the environment. must be taken when removing hair
ers scanned nurses and pharmacists Hazardous drug compounding in or shoe coverings to prevent contam-
wearing gowns during the com- an enclosed environment, such as a ination from spreading to clean ar-
pounding and administration of haz- Class III BSC or an isolator, may not eas. Hair and shoe coverings used in
ardous drugs.95 Of a total of 18 con- require the operator to wear a gown. the hazardous drug handling areas
tamination spots detected, 5 were However, because the process of must be contained, along with used
present on the gowns of nurses after handling drug vials and final prepa- gloves, and discarded as contaminat-
drug administration. No spots were rations, as well as accessing the isola- ed waste.
discovered on the gowns of pharma- tor’s pass-throughs, may present an Work practices. Compounding
cists after compounding. In contrast, opportunity for contamination, the sterile hazardous drugs. Work practic-
researchers using a more sensitive as- donning of a gown is prudent. Coat- es for the compounding of sterile
say placed pads in various body loca- ed gowns may not be necessary for hazardous drugs differ somewhat
tions, both over and under the gowns this use if appropriate gowning prac- with the use of a Class II BSC, a Class
used by the subjects during com- tices are established. Recommenda- III BSC, or an isolator. Good organi-
pounding and administration of cy- tions for use of gowns are summa- zational skills are essential to mini-
clophosphamide and ifosfamide.39 rized in Appendix D. mize contamination and maximize
Workers wore short-sleeved nursing Additional PPE. Eye and face pro- productivity. All activities not re-
uniforms, disposable or cotton tection should be used whenever quiring a critical environment (e.g.,
gowns, and vinyl or latex gloves. there is a possibility of exposure from checking labels, doing calculations)
More contamination was found dur- splashing or uncontrolled aerosoliza- should be completed before access-
ing compounding than administration of hazardous drugs (e.g., when ing the BSC or isolator. All items
tion. Contamination found on the containing a spill or handling a dam- needed for compounding must be
pads placed on the arms of preparers aged shipping carton). In these in- gathered before beginning work.
is consistent with the design and typ- stances, a face shield, rather than This practice should eliminate
ical work practices used in a Class II safety glasses or goggles, is recom- the need to exit the BSC or isolator
BSC, where the hands and arms are mended because of the improved once compounding has begun. Two
extended into the contaminated skin protection afforded by the pairs of gloves should be worn to
work area of the cabinet. Remark- shield. gather hazardous drug vials and sup-
ably, one preparer had contamina- Similar circumstances also war- plies. These gloves should be careful-
tion on the back of the gown, possi- rant the use of a respirator. All work- ly removed and discarded. Fresh
bly indicating touch contamination ers who may use a respirator must be gloves must be donned and appro-
with the Class II BSC during removal fit-tested and trained to use the ap- priately sanitized before aseptic
of the final product. While early propriate respirator according to the manipulation.
guidelines do not contain a maxi- OSHA Respiratory Protection Stan- Only supplies and drugs essential
mum length of time that a gown dard.56,57 A respirator of correct size to compounding the dose or batch
should be worn, Connor’s91 work and appropriate to the aerosol size, should be placed in the work area of
would support a two- to three-hour physical state (i.e., particulate or va- the BSC or main chamber of the iso-
window for a coated gown. Contam- por), and concentration of the air- lator. BSCs and isolators should not
ination of gowns during glove borne drug must be available at all be overcrowded to avoid unneces-
changes must be a consideration. If times. Surgical masks do not provide sary hazardous drug contamination.
the inner pair of gloves requires respiratory protection. Shoe and hair Luer-Lok syringes and connections
changing, a gown change should be coverings should be worn during the must be used whenever possible for
considered. Gowns worn as barrier sterile compounding process to min- manipulating hazardous drugs, as

they are less likely to separate during recognize the limitations of the work area. Being careful not to place
compounding. equipment and address them any sterile objects below them, i.v.
Spiking an i.v. set into a solution through appropriate work practices.1 bags and bottles may be hung from
containing hazardous drugs or prim- The effectiveness of Class II BSCs the bar. All items must be placed well
ing an i.v. set with hazardous drug and isolators in containing contam- within the Class II BSC, away from
solution in an uncontrolled environ- ination depends on proper tech- the unfiltered air at the front barrier.
ment must be avoided. One recom- nique.72 Hazardous drug contamina- By design, the intended work zone
mendation is to attach and prime the tion from the work area of the within the Class II BSC is the area
appropriate i.v. set to the final con- isolator may be brought into the between the front and rear air grilles.
tainer in the BSC or isolator before workroom environment through the The containment characteristics of
adding the hazardous drug. Closed- pass-throughs or air locks and on the Class II BSC are dependent on
system drug-transfer devices should the surfaces of items removed from the airflow through both the front
achieve a dry connection between the the isolators (e.g., the final prepara- and back grilles; these grilles should
administration set and the hazardous tion). Surface decontamination of never be obstructed. Due to the de-
drug’s final container. This connec- the preparation before removal from sign of the Class II BSC, the quality of
tion allows the container to be spiked the isolator’s main chamber should HEPA-filtered air is lowest at the
with a secondary i.v. set and the set to reduce the hazardous drug contami- sides of the work zone, so manipula-
be primed by backflow from a prima- nation that could be transferred to tions should be performed at least six
ry nonhazardous solution. This the workroom, but no wipe-down inches away from each sidewall in the
process may be done outside the BSC procedures have been studied. Sur- horizontal plane. A small waste–
or isolator, reducing the potential for face decontamination may be ac- sharps container may be placed
surface contamination of the i.v. set complished using alcohol, sterile along the sidewall toward the back of
during the compounding process. A water, peroxide, or sodium hy- the BSC. One study has suggested
new i.v. set must be used with each pochlorite solutions, provided the that a plastic-backed absorbent prep-
dose of hazardous drug. Once at- packaging is not permeable to the so- aration pad in a Class II BSC may
tached, the i.v. set must never be re- lution and the labels remain legible interfere with airflow,39 but another
moved from a hazardous drug dose, and intact. Recommendations for study determined that use of a flat
thereby preventing the residual fluid working in BSCs and isolators are firm pad that did not block the grilles
in the bag, bottle, or tubing from summarized in Appendix E. of the cabinet had no effect on air-
leaking and contaminating person- BSCs. Class II BSCs use vertical- flow.96 The use of a large pad that
nel and the environment. flow, HEPA-filtered air (ISO class 5) might block the front or rear grilles
Transport bags must never be as their controlled aseptic environ- must be avoided. In addition, be-
placed in the BSC or in the isolator ment. Before beginning an operation cause a pad may absorb small spills, it
work chamber during compounding in a Class II BSC, personnel should may become a source of hazardous
to avoid inadvertent contamination wash their hands, don an inner pair drug contamination for anything
of the outer surface of the bag. Final of appropriate gloves, and then don a placed upon it. Preparation pads are
preparations must be surface decon- coated gown followed by a second not readily decontaminated and must
taminated after compounding is pair of gloves. The work surface be replaced and discarded after prepa-
complete. In either the BSC or isola- should be cleaned of surface contam- ration of each batch and frequently
tor, clean inner gloves must be worn ination with detergent, sodium hy- during extended batch compounding.
when labeling and placing the final pochlorite, and neutralizer or disin- More information on the design and
preparation into the transport bag. fected with alcohol, depending on use of Class II BSCs is available from
Handling final preparations and trans- when it was last cleaned. For the the NSF/ANSI standard 49-04.62
port bags with gloves contaminated Class II BSC, the front shield must be Isolators. For work in an isolator,
with hazardous drugs will result in the lowered to the proper level to protect all drugs and supplies needed to
transfer of the contamination to other the face and eyes. The operator aseptically compound a dose or
workers. Don fresh gloves whenever should be seated so that his or her batch should be gathered and sani-
there is a doubt as to the cleanliness of shoulders are at the level of the bot- tized with 70% alcohol or appropri-
the inner or outer gloves. tom of the front shield. All drugs and ate disinfectant and readied for
Working in BSCs or isolators. With supplies needed to aseptically com- placement in the pass-through. A
or without ancillary devices, none of pound a dose or batch should be technique described in the literature
the available ventilation or engineer- gathered and sanitized with 70% al- involves the use of a tray that will fit
ing controls can provide 100% pro- cohol or appropriate disinfectant. into the pass-through.97 A large pri-
tection for the worker. Workers must Avoid exiting and reentering the mary sealable bag is placed over the

tray. Labels and a second sealable izing the contents of the vial. Pres- covered with a protective shield. The
(transport) bag, which is used to surization may cause the drug to final container should be placed, us-
contain the final preparation, are spray out around the needle or ing clean gloves, into a sealable bag to
placed into the primary sealable bag through a needle hole or a loose seal, contain any leakage.1
on the tray surface. Vials, syringes, aerosolizing the drug into the work To withdraw hazardous drugs
needles, and other disposables are zone. Pressurization can be avoided from an ampul, the neck or top por-
placed on top of the sealed bag. The by creating a slight negative pressure tion should be gently tapped.98 After
enclosed tray is then taken into the in the vial. Too much negative pres- the neck is wiped with alcohol, a 5-
main chamber of the isolator, where sure, however, can cause leakage μm filter needle or straw should be
the drug and supplies are used to from the needle when it is withdrawn attached to a syringe that is large
compound the dose. The contami- from the vial. The safe handling of enough that it will be not more than
nated materials, including the prima- hazardous drug solutions in vials or three-fourths full when holding the
ry sealable bag, are removed using ampuls requires the use of a syringe drug. The fluid should then be drawn
the closed trash system of the isola- that is no more than three-fourths through the filter needle or straw and
tor, if so equipped, or sealed into a full when filled with the solution, cleared from the needle and hub. Af-
second bag and removed via the which minimizes the risk of the ter this, the needle or straw is ex-
pass-through for disposal as contam- plunger separating from the syringe changed for a needle of similar gauge
inated waste. The dose is then labeled barrel. Once the diluent is drawn up, and length; any air and excess drug
and placed into the second sealable the needle is inserted into the vial should be ejected into a sterile vial
bag for transport. and the plunger is pulled back (to (leaving the desired volume in the
This technique does not address create a slight negative pressure in- syringe); aerosolization should be
contamination on the isolator gloves side the vial), so that air is drawn into avoided. The drug may then be
or gauntlets. Additional work prac- the syringe. Small amounts of diluent transferred to an i.v. bag or bottle. If
tices may include cleaning off should be transferred slowly as equal the dose is to be dispensed in the
the gloves or gauntlets and final volumes of air are removed. The nee- syringe, the plunger should be drawn
preparation after initial compound- dle should be kept in the vial, and the back to clear fluid from the needle
ing and before handling the label and contents should be swirled carefully and hub. The needle should be re-
second sealable bag. Care must be until dissolved. With the vial invert- placed with a locking cap, and the
taken when transferring products ed, the proper amount of drug solu- syringe should be surface decontami-
out of the pass-through and dispos- tion should be gradually withdrawn nated and labeled.
ing of waste through the pass- while equal volumes of air are ex- Training and demonstration of
through or trash chute to avoid acci- changed for solution. The exact vol- competence. All staff who will be
dental contamination. ume needed must be measured while compounding hazardous drugs must
Aseptic technique. Stringent asep- the needle is in the vial, and any ex- be trained in the stringent aseptic
tic technique, described by Wilson cess drug should remain in the vial. and negative-pressure techniques nec-
and Solimando98 in 1981, remains With the vial in the upright position, essary for working with sterile hazard-
the foundation of any procedure in- the plunger should be withdrawn ous drugs. Once trained, staff must
volving the use of needles and sy- past the original starting point to demonstrate competence by an objec-
ringes in manipulating sterile dosage again induce a slight negative pres- tive method, and competency must
forms. This technique, when per- sure before removing the needle. The be reassessed on a regular basis.99
formed in conjunction with negative needle hub should be clear before the Preparation and handling of non-
pressure technique, minimizes the needle is removed. injectable hazardous drug dosage
escape of drug from vials and am- If a hazardous drug is transferred forms. Although noninjectable dos-
puls. Needleless devices have been to an i.v. bag, care must be taken to age forms of hazardous drugs con-
developed to reduce the risk of puncture only the septum of the in- tain varying proportions of drug to
blood-borne pathogen exposure jection port and avoid puncturing nondrug (nonhazardous) compo-
through needle sticks. None of these the sides of the port or bag. After the nents, there is the potential for
devices has been tested for reduction drug solution is injected into the i.v. personnel exposure to and environ-
of hazardous drug contamination. bag, the i.v. port, container, and set mental contamination with the haz-
The appropriateness of these devices (if attached by pharmacy in the BSC ardous components if hazardous
in the safe handling of hazardous or isolator) should be surface decon- drugs are handled (e.g., packaged) by
drugs has not been determined. taminated. The final preparation pharmacy staff. Although most haz-
In reconstituting hazardous drugs should be labeled, including an aux- ardous drugs are not available in liq-
in vials, it is critical to avoid pressur- iliary warning, and the injection port uid formulations, such formulations

are often prescribed for small chil- work is completed. For a 24-hour Administration of hazardous drugs.
dren and adults with feeding tubes. service, the cabinet should be cleaned Policies and procedures governing
Recipes for extemporaneously com- two or three times daily. Cabinets the administration of hazardous
pounded oral liquids may start with used for aseptic compounding must drugs must be jointly developed by
the parenteral form, or they may re- be disinfected at the beginning of nursing and pharmacy for the mutu-
quire that tablets be crushed or cap- the workday, at the beginning of al safety of health care workers.
sules opened. Tablet trituration has each subsequent shift (if compound- These policies should supplement
been shown to cause fine dust forma- ing takes place over an extended pe- policies designed to protect patient
tion and local environmental con- riod of time), and routinely during safety during administration of all
tamination. 100 Procedures for the compounding. drugs. All policies affecting multiple
preparation and the use of equipment Appropriate preparation of mate- departments must be developed with
(e.g., Class I BSCs or bench-top hoods rials used in compounding before in- input from managers and workers
with HEPA filters) must be developed troduction into the Class II BSC or from the affected areas. Extensive
to avoid the release of aerosolized the pass-through of a Class III BSC nursing guidelines for the safe and
powder or liquid into the environ- or isolator, including spraying or appropriate administration of hazard-
ment during manipulation of hazard- wiping with 70% alcohol or appro- ous drugs have been developed by the
ous drugs. Recommendations for priate disinfectant, is also necessary Oncology Nursing Society90,104 and
preparation and handling of nonin- for aseptic compounding. OSHA.2,3 Recommendations for re-
jectable hazardous drug dosage forms The Class II BSC has air plenums ducing exposure to hazardous drugs
are summarized in Appendix F. that handle contaminated air. These during administration in all practice
Decontamination, deactivation, plenums are not designed to allow settings are listed in Appendix G.
and cleaning. Decontamination may surface decontamination, and many Spill management. Policies and
be defined as cleaning or deactivat- of the contaminated surfaces (ple- procedures must be developed to at-
ing. Deactivating a hazardous sub- nums) cannot be reached for surface tempt to prevent spills and to govern
stance is preferred, but no single cleaning. The area under the work cleanup of hazardous drug spills.
process has been found to deactivate tray should be cleaned at least Written procedures must specify
all currently available hazardous monthly to reduce the contamina- who is responsible for spill manage-
drugs. The use of alcohol for disin- tion level in the Class II BSC (and in ment and must address the size and
fecting the BSC or isolator will not isolators, where appropriate). scope of the spill. Spills must be con-
deactivate any hazardous drugs Surface decontamination may be tained and cleaned up immediately
and may result in the spread of con- accomplished by the transfer of haz- by trained workers.
tamination rather than any actual ardous drug contamination from the Spill kits containing all of the ma-
cleaning.30,47 surface of a nondisposable item to terials needed to clean up spills of
Decontamination of BSCs and disposable ones (e.g., wipes, gauze, hazardous drugs should be assem-
isolators should be conducted per towels). Although the outer surface bled or purchased (Appendix H).
manufacturer recommendations. of vials containing hazardous drugs These kits should be readily available
The MSDSs for many hazardous has been shown to be contaminated in all areas where hazardous drugs
drugs recommend sodium hy- with hazardous drugs,30,54,55 and haz- are routinely handled. A spill kit
pochlorite solution as an appropriate ardous drug contamination has been should accompany delivery of inject-
deactivating agent. 101 Researchers found on the outside of final prepa- able hazardous drugs to patient care
have shown that strong oxidizing rations,30 no wipe-down procedures areas even though they are transport-
agents, such as sodium hypochlorite, have been studied. The amount of ed in a sealable plastic bag or con-
are effective deactivators of many hazardous drug contamination tainer. If hazardous drugs are being
hazardous drugs.102,103 There is cur- placed into the BSC or isolator may prepared or administered in a non-
rently one commercially available be reduced by surface decontamina- routine area (e.g., home setting, un-
product, SurfaceSafe (SuperGen, tion (i.e., wiping down) of hazardous usual patient care area), a spill kit
Dublin, CA), that provides a system drug vials. While no wipe-down pro- and respirator must be obtained by
for decontamination and deactiva- cedures have been studied, the use of the drug handler. Signs should be
tion using sodium hypochlorite, gauze moistened with alcohol, sterile available to warn of restricted access
detergent, and thiosulfate neutraliz- water, peroxide, or sodium hy- to the spill area.
er. A ventilated cabinet that runs pochlorite solutions may be effective. Only trained workers with appro-
continuously should be cleaned be- The disposable item, once contami- priate PPE and respirators should at-
fore the day’s operations begin and at nated, must be contained and dis- tempt to manage a hazardous drug
regular intervals or when the day’s carded as contaminated waste. spill. All workers who may be re-

quired to clean up a spill of hazard- considered hazardous waste. The of trace chemotherapy waste, 110
ous drugs must receive proper train- listed drugs include epinephrine, nic- “RCRA-empty” containers, needles,
ing in spill management and in otine, and physostigmine, as well as syringes, trace-contaminated gowns,
the use of PPE and NIOSH-certified nine chemotherapy drugs: arsenic tri- gloves, pads, and empty i.v. sets may
respirators. oxide, chlorambucil, cyclophospha- be collected and incinerated at a reg-
The circumstances and handling mide, daunomycin, diethylstilbestrol, ulated medical waste incinerator.
of spills should be documented. Staff melphalan, mitomycin C, streptozo- Sharps used in the preparation of
and nonemployees exposed to a cin, and uracil mustard. They require hazardous drugs should not be
hazardous drug spill should also handling, containment, and disposal placed in red sharps containers or
complete an incident report or expo- as RCRA hazardous waste. needle boxes, since these are most
sure form and report to the desig- The RCRA allows for the exemp- frequently disinfected by autoclaving
nated emergency service for initial tion of “empty containers” from haz- or microwaving, not by incineration,
evaluation. ardous waste regulations. Empty and pose a risk of aerosolization to
All spill materials must be dis- containers are defined as those that waste-handling employees.
posed of as hazardous waste.105 Rec- have held U-listed or characteristic Bulk hazardous drug waste. While
ommendations for spill cleanup pro- wastes and from which all wastes not official, the term bulk hazardous
cedure are summarized in Appendix I. have been removed that can be re- drug waste has been used to differen-
Worker contamination. Proce- moved using the practices commonly tiate containers that have held either
dures must be in place to address employed to remove materials (1) RCRA-listed or characteristic
worker contamination, and proto- from that type of container and no hazardous waste or (2) any hazard-
cols for medical attention must be more than 3% by weight of the ous drugs that are not RCRA empty
developed before the occurrence of total capacity of the container re- or any materials from hazardous
any such incident. Emergency kits mains in the container.109 Disposal drug spill cleanups. These wastes
containing isotonic eyewash supplies guidelines developed by the National should be managed as hazardous
(or emergency eyewashes, if avail- Institutes of Health (NIH) and pub- waste.
able) and soap must be immediately lished in 1984 coined the term Hazardous drugs not listed as haz-
available in areas where hazardous “trace-contaminated” waste using ardous waste. The federal RCRA reg-
drugs are handled. Workers who are the 3% rule.110 Note that a container ulations have not kept up with drug
contaminated during the spill or spill that has held an acute hazardous development, as there are over 100
cleanup or who have direct skin or waste listed in §§261.31, 261.32, or hazardous drugs that are not listed as
eye contact with hazardous drugs re- 261.33(e), such as arsenic trioxide, is hazardous waste, including hormon-
quire immediate treatment. OSHA- not considered empty by the 3% al agents. In some states, such as
recommended steps for treatment rule,111 and that spill residues from Minnesota, these must be managed
are outlined in Appendix J. cleanup of hazardous agents are con- as hazardous waste. In other states,
Hazardous waste containment sidered hazardous waste.105 organizations should manage these
and disposal. In 1976, the Resource In addition, many states are au- drugs as hazardous waste as a best-
Conservation and Recovery Act thorized to implement their own management practice until federal
(RCRA) was enacted to provide a hazardous waste programs, and re- regulations can be updated.
mechanism for tracking hazardous quirements under these programs Hazardous waste and mixed
waste from its generation to dispos- may be more stringent than those of infectious–hazardous waste. Most
al.106 Regulations promulgated under the EPA. State and local regulations hazardous waste vendors are not per-
RCRA are enforced by the Environ- must be considered when establish- mitted to manage regulated medical
mental Protection Agency and apply ing a hazardous waste policy for a waste or infectious waste; therefore,
to pharmaceuticals and chemicals specific facility. they cannot accept used needles and
discarded by pharmacies, hospitals, General categories of hazardous items contaminated with squeezable,
clinics, and other commercial enti- waste found in health care settings flakable, or drippable blood. Organi-
ties. The RCRA outlines four “char- would include trace-contaminated zations should check carefully with
acteristics” of hazardous waste107 and hazardous waste, bulk hazardous their hazardous waste vendors to
contains lists of agents that are to be waste, hazardous drugs not listed as ensure acceptance of all possible
considered hazardous waste when hazardous waste, and hazardous waste hazardous waste, including mixed
they are discarded.108 Any discarded and mixed infectious–hazardous infectious waste, if needed. Once
drug that is on one of the lists (a waste. hazardous waste has been identified,
“listed” waste) or meets one of the Trace-contaminated hazardous it must be collected and stored ac-
criteria (a “characteristic” waste) is drug waste. By the NIH definition cording to specific EPA and Depart-

ment of Transportation require- feeding, or attempting to conceive or circumstances and to take into ac-
ments.112 Properly labeled, leakproof, father a child. Employees’ physicians count evolving federal, state, and
and spill-proof containers of nonre- should be involved in making these local regulations, as well as the re-
active plastic are required for areas determinations. quirements of appropriate accredit-
where hazardous waste is generated. All workers who handle hazard- ing institutions.
Hazardous drug waste may be initial- ous drugs should be routinely moni-
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104. Polovich M, Belcher C, Glynn-Tucker 5. Appropriate decontamination within the Appendix D—Recommendations for
EM et al. Safe handling of hazardous cabinet must be completed before the cab- use of gowns
drugs. Pittsburgh: Oncology Nursing inet is accessed via pass-throughs or re-
Society; 2003. movable front panels. 1. Gowns should be worn during com-
105. 40 C.F.R. 261.33. 6. Gloves or gauntlets must not be replaced pounding, during administration, when
106. Resource Conservation and Recovery before completion of appropriate decon- handling waste from patients recently
Act of 1976. 42 U.S.C. 82 §6901-92. tamination within the cabinet. treated with hazardous drugs, and when
107. 40 C.F.R. 261.20-24C. 7. Surface decontamination of final prepara- cleaning up spills of hazardous drugs.
108. 40 C.F.R. 261.3.38D. tions must be done before labeling and 2. Select disposable gowns of material tested
109. 40 C.F.R. 261.7. placing into the pass-through. to be protective against the hazardous
110. Vaccari PL, Tonat K, DeChristoforo R et 8. Final preparations must be placed into a drugs to be used.
al. Disposal of antineoplastic wastes at transport bag while in the pass-through 3. Coated gowns must be worn no longer
the National Institutes of Health. Am J for removal from the cabinet. than three hours during compounding
Hosp Pharm. 1984; 41:87-93. and changed immediately when damaged
111. 40 C.F.R. 261.7(b)(1)-(3). Appendix C—Recommendations for or contaminated.
112. 49 C.F.R. 172.0-.123,173,178,179. 4. Remove gowns with care to avoid spread-
use of gloves ing contamination. Specific procedures
113. 29 C.F.R. 1910.120(e)(3)(i).
1. Wear double gloves for all activities infor removal must be established and
114. 29 C.F.R. 1910.120(q)(1-6).
volving hazardous drugs. Double gloves followed.
115. 40 C.F.R. 260-8,270.
must be worn during any handling of 5. Dispose of gowns immediately upon
hazardous drug shipping cartons or removal.
Appendix A—Recommendations for drug vials, compounding and adminis- 6. Contain and dispose of contaminated
use of Class II BSCs tration of hazardous drugs, handling gowns as contaminated waste.
1. The use of a Class II BSC must be accom- of hazardous drug waste or waste from 7. Wash hands after removing and disposing
panied by a stringent program of work patients recently treated with hazard- of gowns.
practices, including training, demonstrat- ous drugs, and cleanup of hazardous
ed competence, contamination reduction, drug spills. Appendix E—Recommendations for
and decontamination. 2. Select powder-free, high-quality gloves
made of latex, nitrile, polyurethane, neo- working in BSCs and isolators
2. Only a Class II BSC with outside exhaust
should be used for compounding hazard- prene, or other materials that meet the 1. The use of a Class II or III BSC or isolator
ous drugs; type B2 total exhaust is pre- ASTM standard for chemotherapy must be accompanied by a stringent
ferred. Total exhaust is required if the haz- gloves. program of work practices, including
ardous drug is known to be volatile.4 3. Inspect gloves for visible defects. operator training and demonstrated
3. Without special design considerations, 4. Sanitize gloves with 70% alcohol or other competence, contamination reduction,
Class II BSCs are not recommended in tra- appropriate disinfectant before perform- and decontamination.
ditional, positive-pressure cleanrooms, ing any aseptic compounding activity. 2. Do not place unnecessary items in the
where contamination from hazardous 5. Change gloves every 30 minutes during work area of the cabinet or isolator where
drugs may result in airborne contamina- compounding or immediately when hazardous drug contamination from
tion that may spread from the open front damaged or contaminated. compounding may settle on them.
to surrounding areas. 6. Remove outer gloves after wiping down 3. Do not overcrowd the BSC or isolator.
4. Consider using closed-system drug- final preparation but before labeling or 4. Gather all needed supplies before begin-
transfer devices while compounding haz- removing the preparation from the ning compounding. Avoid exiting and
ardous drugs in a Class II BSC; evidence BSC. reentering the work area of the BSC or
documents a decrease in drug contami- 7. Outer gloves must be placed in a contain- isolator.
nants inside a Class II BSC when such de- ment bag while in the BSC. 5. Appropriate handling of the preparation
vices are used.4 8. In an isolator, a second glove must be in the BSC or pass-through of the iso-
5. Reduce the hazardous drug contamina- worn inside the fixed-glove assembly. lator, including spraying or wiping with
tion burden in the Class II BSC by wiping 9. In an isolator, fixed gloves or gauntlets 70% alcohol or another appropriate
down hazardous drug vials before placing must be surface cleaned after com- disinfectant, is necessary for aseptic
them in the BSC. pounding is completed to avoid spread- compounding.
ing hazardous drug contamination to 6. Reduce the hazardous drug contamina-
other surfaces. tion burden in the BSC or isolator by
Appendix B—Recommendations for wiping down hazardous drug vials before
10. Clean gloves (e.g., the clean inner gloves)
use of Class III BSCs and isolators should be used to surface decontaminate placing them in the BSC or isolator.
1. Only a ventilated cabinet designed to pro- the final preparation, place the label onto 7. Transport bags must never be placed in
tect workers and adjacent personnel from the final preparation, and place it into the the BSC or the isolator work chamber
exposure and to provide an aseptic envi- pass-through. during compounding to avoid inadvert-
ronment may be used to compound sterile 11. Don fresh gloves to complete the final ent contamination of the outside surface
hazardous drugs. check, place preparation into a clean of the bag.
2. Only ventilated cabinets that are designed transport bag, and remove the bag from 8. Final preparations should be surface de-
to contain aerosolized drug product with- the pass-through. contaminated within the BSC or isolator
in the cabinet should be used to com- 12. Wash hands before donning and after re- and placed into the transport bags in the
pound hazardous drugs. moving gloves. BSC or in the isolator pass-through, tak-
3. The use of a Class III BSC or isolator 13. Remove gloves with care to avoid con- ing care not to contaminate the outside of
must be accompanied by a stringent pro- tamination. Specific procedures for re- the transport bag.
gram of work practices, including oper- moval must be established and followed. 9. Decontaminate the work surface of the
ator training and demonstrated com 14. Gloves should be removed and contained BSC or isolator before and after com-
petence, contamination reduction, and inside the Class II BSC or isolator. pounding per the manufacturer’s recom-
decontamination. 15. Change gloves after administering a dose mendations or with detergent, sodium
4. Decontamination of the Class III BSC or of hazardous drugs or when leaving the hypochlorite solution, and neutralizer.
isolator must be done in a way that con- immediate administration area. 10. Decontaminate all surfaces of the BSC or
tains any hazardous drug surface contami- 16. Dispose of contaminated gloves as con- isolator at the end of the batch, day, or
nation during the cleaning process. taminated waste. shift, as appropriate to the workflow.

Typically, a BSC or isolator in use 24 paring a solution or an ointment), work- that does not contain hazardous drugs or
hours a day would require decontamina- ers should wear nonpermeable gowns by the backflow method.
tion two or three times daily. Disinfect and double gloves. Compounding should 14. Place a gauze pad under the connection at
the BSC or isolator before compounding take place in a ventilated cabinet. injection ports during administration to
a dose or batch of sterile hazardous drugs. 8. Compounding nonsterile forms of haz- catch leaks.
11. Wipe down the outside of the Class II ardous drugs in equipment designated 15. Use the transport bag as a containment
BSC front opening and the floor in front for sterile products must be undertaken bag for materials contaminated with haz-
of the BSC with detergent, sodium hy- with care. Appropriate containment, de- ardous drugs, drug containers, and sets.
pochlorite solution, and neutralizer at activation, and disinfection techniques 16. Discard hazardous drug containers with
least daily. must be utilized. the administration sets attached; do not
12. Seal and then decontaminate surfaces of 9. Hazardous drugs should be dispensed in remove the set.
waste and sharps containers before re- the final dose and form whenever possi- 17. Wash surfaces that come into contact
moving from the BSC or isolator. ble. Unit-of-use containers for oral with hazardous drugs with detergent, so-
13. Decontamination is required after any liquids have not been tested for contain- dium hypochlorite solution, and neutral-
spill in the BSC or isolator during ment properties. Most exhibit some izer, if appropriate.
compounding. spillage during preparation or use. Cau- 18. Wearing gloves, contain and dispose of
14. Seal all contaminated materials (e.g., tion must be exercised when using these materials contaminated with hazardous
gauze, wipes, towels, wash or rinse water) devices. drugs and remaining PPE as contaminat-
in bags or plastic containers and discard 10. Bulk containers of liquid hazardous ed waste.
as contaminated waste. drugs, as well as specially packaged com- 19. Hazardous drug waste container must be
15. Decontamination of the Class III BSC or mercial hazardous drugs (e.g., Neoral sufficiently large to hold all discarded
isolator must be done in a way that con- [manufactured by Novartis]), must be material, including PPE.
tains any hazardous drug surface con- handled carefully to avoid spills. These 20. Do not push or force materials contami-
tamination during the cleaning process. containers should be dispensed and nated with hazardous drugs into the haz-
16. Appropriate decontamination within the maintained in sealable plastic bags to ardous drug waste container.
cabinet must be completed before the contain any inadvertent contamination. 21. Carefully remove, contain, and discard
cabinet is accessed via the pass-throughs 11. Disposal of unused or unusable nonin- gloves. Wash hands thoroughly after re-
or removable front panels. jectable dosage forms of hazardous drugs moving gloves.
17. Gloves or gauntlets must not be replaced should be performed in the same manner Intramuscular or subcutaneous administration
before completion of appropriate decon- as for hazardous injectable dosage forms 1. The use of double gloves is required.
tamination within the cabinet. and waste. 2. Gather all necessary equipment and sup-
18. Surface decontamination of final prepa- plies, including PPE.
rations must be done before labeling and Appendix G—Recommendations for 3. Use Luer-Lok safety needles or retracting
placing into the pass-through. reducing exposure to hazardous drugs needles or shields.
19. Final preparations must be placed into a 4. Syringes should have Luer-Lok connec-
transport bag while in the pass-through during administration in all practice tions and be less than three-fourths full.
for removal from the cabinet. settings104 5. Designate a workplace for handling haz-
Intravenous administration ardous drugs.
Appendix F—Recommendations for 1. The use of gloves, gown, and face shield 6. Have a spill kit and hazardous drug waste
compounding and handling (as needed for splashing) is required. container readily available.
2. Gather all necessary equipment and sup- 7. Procedure for gloving: Wash hands; don
noninjectable hazardous drug dosage plies, including PPE. double gloves.
forms 3. Use needleless systems whenever possible. 8. Always work below eye level.
1. Hazardous drugs should be labeled or 4. Use Luer-Lok fittings for all needleless 9. Visually examine hazardous drug dose
otherwise identified as such to prevent systems, syringes, needles, infusion tub- while still contained in transport bag.
improper handling. ing, and pumps. 10. If hazardous drug dose appears intact, re-
2. Tablet and capsule forms of hazardous 5. Needleless systems may result in droplets move it from the transport bag.
drugs should not be placed in automated leaking at connection points; use gauze 11. Remove the syringe cap and connect ap-
counting machines, which subject them pads to catch leaks. propriate safety needle.
to stress and may introduce powdered 6. Designate a workplace for handling haz- 12. Do not expel air from syringe or prime
contaminants into the work area. ardous drugs. the safety needle.
3. During routine handling of noninjectable 7. Have a spill kit and hazardous drug waste 13. After administration, discard hazardous
hazardous drugs and contaminated container readily available. drug syringes (with the safety needle at-
equipment, workers should wear two 8. Procedure for gowning and gloving: tached) directly into a hazardous drug
pairs of gloves that meet the ASTM stan- Wash hands, don first pair of gloves, don waste container.
dard for chemotherapy gloves.85 gown and face shield, and then don sec- 14. Wearing gloves, contain and dispose of
4. Counting and pouring of hazardous ond pair of gloves. Gloves should extend materials contaminated with hazardous
drugs should be done carefully, and clean beyond the elastic or knit cuff of the drugs.
equipment should be dedicated for use gown. Double-gloving requires one glove 15. Do not push or force materials contami-
with these drugs. to be worn under the cuff of the gown nated with hazardous drugs into the haz-
5. Contaminated equipment should be and the second glove over the cuff. ardous drug waste container.
cleaned initially with gauze saturated 9. Always work below eye level. 16. Carefully remove, contain, and discard
with sterile water; further cleaned with 10. Visually examine hazardous drug dose gloves.
detergent, sodium hypochlorite solution, while it is still contained in transport bag. 17. Wash hands thoroughly after removing
and neutralizer; and then rinsed. The 11. If hazardous drug dose appears intact, re- gloves.
gauze and rinse should be contained and move it from the transport bag. Oral administration
disposed of as contaminated waste. 12. Place a plastic-backed absorbent pad un- 1. Double gloves are required, as is a face
6. Crushing tablets or opening capsules der the administration area to absorb shield if there is a potential for spraying,
should be avoided; liquid formulations leaks and prevent drug contact with the aerosolization, or splashing.
should be used whenever possible. patient’s skin. 2. Workers should be aware that tablets or
7. During the compounding of hazardous 13. If priming occurs at the administration capsules may be coated with a dust of
drugs (e.g., crushing, dissolving, or pre- site, prime i.v. tubing with an i.v. solution residual hazardous drug that could be in-

haled, absorbed through the skin, ingest- 7. Carefully remove any broken glass frag- 5. Obtain medical attention.
ed, or spread to other locations and that ments and place them in a puncture- 6. Document exposure in employee’s medi-
liquid formulations may be aerosolized resistant container. cal record and medical surveillance log.
or spilled. 8. Absorb liquids with spill pads. 7. Supplies for emergency treatment (e.g.,
3. No crushing or compounding of oral 9. Absorb powder with damp disposable soap, eyewash, sterile saline for irrigation)
hazardous drugs may be done in an un- pads or soft toweling. should be immediately located in any area
protected environment. 10. Spill cleanup should proceed progres- where hazardous drugs are compounded
4. Gather all necessary equipment and sup- sively from areas of lesser to greater or administered.
plies, including PPE. contamination.
5. Designate a workplace for handling haz- 11. Completely remove and place all contam- Glossary
ardous drugs. inated material in the disposal bags.
6. Have a spill kit and hazardous drug waste 12. Rinse the area with water and then clean Antineoplastic drug: A chemotherapeutic
container readily available. with detergent, sodium hypochlorite so- agent that controls or kills cancer cells. Drugs
7. Procedure for gloving: Wash hands and lution, and neutralizer. used in the treatment of cancer are cytotoxic but
don double gloves. 13. Rinse the area several times and place all are generally more damaging to dividing cells
8. Always work below eye level. materials used for containment and than to resting cells.4
9. Visually examine hazardous drug dose cleanup in disposal bags. Seal bags and Aseptic: Free of living pathogenic organisms
while it is still contained in transport bag. place them in the appropriate final con- or infected materials.4
10. If hazardous drug dose appears intact, re- tainer for disposal as hazardous waste. Biological-safety cabinet (BSC): A BSC may
move it from the transport bag. 14. Carefully remove all PPE using the inner be one of several types.4
11. Place a plastic-backed absorbent pad on gloves. Place all disposable PPE into dis- Class I BSC: A BSC that protects personnel
the work area, if necessary, to contain any posal bags. Seal bags and place them into and the work environment but does not protect
spills. the appropriate final container. the product. It is a negative-pressure, ventilated
12. After administration, wearing double 15. Remove inner gloves; contain in a small, cabinet usually operated with an open front and
gloves, contain and dispose of materials sealable bag; and then place into the ap- a minimum face velocity at the work opening of
contaminated with hazardous drugs into propriate final container for disposal as at least 75 ft/min. A class I BSC is similar in
the hazardous drug waste container. hazardous waste. design to a chemical fume hood except that all of
13. Do not push or force materials contami- 16. Wash hands thoroughly with soap and the air from the cabinet is exhausted through a
nated with hazardous drugs into the haz- water.
high-efficiency particulate air (HEPA) filter (ei-
ardous drug waste container. 17. Once a spill has been initially cleaned,
14. Carefully remove, contain, and discard have the area recleaned by housekeeping, ther into the laboratory or to the outside).
gloves. janitorial staff, or environmental services. Class II BSC: A ventilated BSC that protects
15. Wash hands thoroughly after removing Spills in a BSC or isolator personnel, the product, and the work environ-
gloves. 1. Spills occurring in a BSC or isolator ment. A Class II BSC has an open front with
should be cleaned up immediately. inward airflow for personnel protection, down-
Appendix H—Recommended contents 2. Obtain a spill kit if the volume of the spill ward HEPA-filtered laminar airflow for product
exceeds 30 mL or the contents of one drug protection, and HEPA-filtered exhausted air for
of hazardous drug spill kit
vial or ampul. environmental protection.
1. Sufficient supplies to absorb a spill of 3. Utility gloves (from spill kit) should be Type A1 (formerly type A): These Class II
about 1000 mL (volume of one i.v. bag or worn to remove broken glass in a BSC or an BSCs maintain a minimum inflow velocity of 75
bottle). isolator. Care must be taken not to damage ft/min, have HEPA-filtered down-flow air that is
2. Appropriate PPE to protect the worker the fixed-glove assembly in the isolator. a portion of the mixed down-flow and inflow air
during cleanup, including two pairs of dis- 4. Place glass fragments in the puncture- from a common plenum, may exhaust HEPA-
posable gloves (one outer pair of heavy resistant hazardous drug waste container
utility gloves and one pair of inner gloves); filtered air back into the laboratory or to the
located in the BSC or discard into the ap- environment through an exhaust canopy, and
nonpermeable, disposable protective gar- propriate waste receptacle of the isolator.
ments (coveralls or gown and shoe cov- may have positive-pressure contaminated ducts
5. Thoroughly clean and decontaminate the and plenums that are not surrounded by
ers); and face shield. BSC or isolator.
3. Absorbent, plastic-backed sheets or spill negative-pressure plenums. They are not suitable
6. Clean and decontaminate the drain spill-
pads. for use with volatile toxic chemicals and volatile
age trough located under the Class II
4. Disposable toweling. BSC or similarly equipped Class III BSC or radionucleotides.
5. At least two sealable, thick plastic hazard- isolator. Type A2 (formerly type B3): These Class II
ous waste disposal bags (prelabeled with 7. If the spill results in liquid being intro- BSCs maintain a minimum inflow velocity of
an appropriate warning label). duced onto the HEPA filter or if powdered 100 ft/min, have HEPA-filtered down-flow air
6. One disposable scoop for collecting glass aerosol contaminates the “clean side” of that is a portion of the mixed down-flow and
fragments. the HEPA filter, use of the BSC or isolator inflow air from a common exhaust plenum, may
7. One puncture-resistant container for glass should be suspended until the equipment exhaust HEPA-filtered air back into the labora-
fragments. has been decontaminated and the HEPA tory or to the environment through an exhaust
filter replaced. canopy, and have all contaminated ducts and
Appendix I—Recommendations for plenums under negative pressure or surrounded
spill cleanup procedure Appendix J—OSHA-recommended by negative-pressure ducts and plenums. If these
General steps for immediate treatment of cabinets are used for minute quantities of vola-
1. Assess the size and scope of the spill. Call workers with direct skin or eye contact tile toxic chemicals and trace amounts of radio-
for trained help, if necessary. nucleotides, they must be exhausted through
with hazardous drugs3
2. Spills that cannot be contained by two properly functioning exhaust canopies.
spill kits may require outside assistance. 1. Call for help, if needed. Type B1: These Class II BSCs maintain a min-
3. Post signs to limit access to spill area. 2. Immediately remove contaminated imum inflow velocity of 100 ft/min, have HEPA-
4. Obtain spill kit and respirator. clothing. filtered down-flow air composed largely of un-
5. Don PPE, including inner and outer 3. Flood affected eye with water or isotonic contaminated, recirculated inflow air, exhaust
gloves and respirator. eyewash for at least 15 minutes.
most of the contaminated down-flow air
6. Once fully garbed, contain spill using spill 4. Clean affected skin with soap and water;
through a dedicated duct exhausted to the at-
kit. rinse thoroughly.

mosphere after passing it through a HEPA filter, disposable item to disposable ones (e.g., wipes, operations within the isolator to be conducted
and have all contaminated ducts and plenums un- gauze, towels). through a fixed-glove assembly without compro-
der negative pressure or surrounded by negative- Disinfecting: Removal of viable organism mising asepsis or containment.4
pressure ducts and plenums. If these cabinets are from surfaces using 70% alcohol or other appro- Aseptic isolator: A ventilated isolator de-
used for work involving minute quantities of priate disinfectant prior to compounding of ster- signed to exclude external contamination from
volatile toxic chemicals and trace amounts of ra- ile hazardous drugs. entering the critical zone inside the isolator.4
dionucleotides, the work must be done in the Engineering controls: Devices designed to Aseptic containment isolator: A ventilated
directly exhausted portion of the cabinet. eliminate or reduce worker exposures to chemi- isolator designed to meet the requirements
Type B2 (total exhaust): These Class II BSCs cal, biological, radiological, ergonomic, or physi- of both an aseptic isolator and a containment
maintain a minimum inflow velocity of 100 ft/min, cal hazards. Examples include laboratory fume isolator.4
have HEPA-filtered down-flow air drawn from hoods, glove bags, retracting syringe needles, Containment isolator: A ventilated isolator
the laboratory or the outside, exhaust all inflow sound-dampening materials to reduce noise lev- designed to prevent the toxic materials processed
and down-flow air to the atmosphere after filtra- els, safety interlocks, and radiation shielding.4 inside it from escaping to the surrounding
tion through a HEPA filter without recirculation Genotoxic: Capable of damaging DNA and environment.4
inside the cabinet or return to the laboratory, leading to mutations.4 Laboratory coat: A disposable or reusable
and have all contaminated ducts and plenums Glove box: A controlled environment work open-front coat, usually made of cloth or other
under negative pressure or surrounded by direct- enclosure providing a primary barrier from the permeable material.4
ly exhausted negative-pressure ducts and ple- work area. Operations are performed through Material safety data sheet: Contains sum-
nums. These cabinets may be used with volatile sealed gloved openings to protect the worker, the maries provided by the manufacturer to describe
toxic chemicals and radionucleotides. ambient environment, and/or the product.4 the chemical properties and hazards of specific
Class III BSC: A BSC with a totally enclosed, Hazardous drug: Any drug identified by at chemicals and ways in which workers can protect
ventilated cabinet of gastight construction in least one of the following six criteria: carcinoge- themselves from exposure to these chemicals.4
which operations are conducted through at- nicity, teratogenicity or developmental toxicity, Mutagenic: Capable of increasing the sponta-
tached rubber gloves and observed through a reproductive toxicity in humans, organ toxicity neous mutation rate by causing changes in DNA.4
nonopening view window. This BSC is main- at low doses in humans or animals, genotoxicity, Personal protective equipment (PPE):
tained under negative pressure of at least 0.50 in and new drugs that mimic existing hazardous Items such as gloves, gowns, respirators, goggles,
of water gauge, and air is drawn into the cabinet drugs in structure or toxicity.4 and face shields that protect individual workers
through HEPA filters. The exhaust air is treated by Hazardous waste: Any waste that is an from hazardous physical or chemical exposures.4
double HEPA filtration or single HEPA filtration– RCRA-listed hazardous waste [40 C.F.R. 261.30– Respirator: A type of PPE that prevents
incineration. Passage of materials in and out of .33] or that meets an RCRA characteristic of ig- harmful materials from entering the respiratory
the cabinet is generally performed through a dunk nitability, corrosivity, reactivity, or toxicity as system, usually by filtering hazardous agents
tank (accessible through the cabinet floor) or a defined in 40 C.F.R. 261.21–.24.4 from workplace air. A surgical mask does not
double-door pass-through box (such as an auto- Health care settings: All hospitals, medical offer respiratory protection.4
clave) that can be decontaminated between uses. clinics, outpatient facilities, physicians’ offices, Risk assessment: Characterization of poten-
Chemotherapy drug: A chemical agent used retail pharmacies, and similar facilities dedicated tially adverse health effects from human expo-
to treat diseases. The term usually refers to a drug to the care of patients.4 sure to environmental or occupational hazards.
used to treat cancer.4 Health care workers: All workers who are Risk assessment can be divided into five major
Chemotherapy glove: A medical glove that involved in the care of patients. These include steps: hazard identification, dose–response as-
has been approved by FDA for use when han- pharmacists, pharmacy technicians, nurses (reg- sessment, exposure assessment, risk character-
dling antineoplastic drugs.4 istered nurses, licensed practical nurses, nurses’ ization, and risk communication.4
Chemotherapy waste: Discarded items such aides, etc.), physicians, home health care work- Surface decontamination: Transfer of haz-
as gowns, gloves, masks, i.v. tubing, empty bags, ers, and environmental services workers (house- ardous drug contamination from the surface of
empty drug vials, needles, and syringes used keeping, laundry, and waste disposal).4 nondisposable items to disposable ones (e.g.,
while preparing and administering antineoplas- HEPA filter: Filter rated 99.97% efficient in wipes, gauze, towels). No procedures have been
tic agents.4 capturing particles 0.3-μm in diameter.4 studied for surface decontamination of hazard-
Closed system: A device that does not ex- Horizontal-laminar-airflow hood (horizontal- ous drug contaminated surfaces. The use of
change unfiltered air or contaminants with the laminar-airflow clean bench): A device that gauze moistened with alcohol, sterile water, per-
adjacent environment.4 protects the work product and the work area by oxide, or sodium hypochlorite solutions may be
Closed-system drug-transfer device: A supplying HEPA-filtered air to the rear of the effective. The disposable item, once contaminat-
drug-transfer device that mechanically prohibits cabinet and producing a horizontal flow across ed, must be contained and discarded as hazard-
the transfer of environmental contaminants into the work area and out toward the worker.4 ous waste.
the system and the escape of hazardous drug or Isolator: A device that is sealed or is supplied Ventilated cabinet: A type of engineering
vapor concentrations outside the system.4 with air through a microbially retentive filtration control designed for purposes of worker protec-
Cytotoxic: A pharmacologic compound that system (HEPA minimum) and may be reproduc- tion (as used in these guidelines). These devices
is detrimental or destructive to cells within the ibly decontaminated. When closed, an isolator are designed to minimize worker exposures by
body.4 uses only decontaminated interfaces (when nec- controlling emissions of airborne contaminants
Deactivation: Treating a chemical agent essary) or rapid transfer ports for materials trans- through (1) the full or partial enclosure of a po-
(such as a hazardous drug) with another chemi- fer. When open, it allows for the ingress and tential contaminant source, (2) the use of airflow
cal, heat, ultraviolet light, or another agent to egress of materials through defined openings capture velocities to capture and remove air-
create a less hazardous agent.4 that have been designed and validated to pre- borne contaminants near their point of genera-
Decontamination: Inactivation, neutraliza- clude the transfer of contaminants or unfiltered tion, and (3) the use of air pressure relationships
tion, or removal of toxic agents, usually by air to adjacent environments. An isolator can be that define the direction of airflow into the cabi-
chemical means.4 Surface decontamination may used for aseptic processing, for containment of net. Examples of ventilated cabinets include
be accomplished by the transfer of hazardous potent compounds, or for simultaneous asepsis BSCs, containment isolators, and laboratory
drug contamination from the surface of a non- and containment. Some isolator designs allow fume hoods.4

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ASHP REPORTS Handling hazardous drugs

ASHP Guidelines on Handling Hazardous Drugs

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future revisions are likely to address Pharmacists.

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Recommendations of the packing cartons and onto the respirator, is recommended.56,57 As

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