BRIEFING
800 Hazardous Drugs—Handling in Healthcare Settings. Because there is no
existing USP chapter for this topic, the Compounding Expert Committee and the
Compounding with Hazardous Drugs Expert Panel propose this new general chapter to
guide the handling of hazardous drugs in healthcare settings. This new general chapter
has been created to identify the requirements for receipt, storage, mixing, preparing,
compounding, dispensing, and administration of hazardous drugs to protect the patient,
healthcare personnel, and environment. Facility requirements that differ from general
chapter 797 Pharmaceutical Compounding—Sterile Preparations and this chapter
will be harmonized. These differences include the following:
1. Elimination of the current allowance in 797 for facilities that prepare a low
volume of hazardous drugs that permits placement of a BSC or CACI in a nonnegative pressure room. All hazardous drug compounding shall be done in a
separate area designated for hazardous drug compounding.
2. Allowance for a Containment Segregated Compounding Area (C-SCA), a
separate, negative pressure room with at least 12 air changes per hour (ACPH)
for use with compounding hazardous drugs. Low- and medium-risk hazardous
drug CSP may be prepared in a BSC located in a C-SCA, provided the beyonduse date of the CSP does not exceed 12 hours. A CACI that meets the
requirements in 797 may be used for hazardous drug compounding if it is
placed in a C-SCA.
The proposed chapter is posted online at www.usp.org/usp-nf/notices/compounding-notice with
line numbers. To ensure that your comments are received and addressed, please provide the
line numbers corresponding to your comments when submitting comments to
CompoundingSL@usp.org.
(CMP: J. Sun.) Correspondence Number—C139868
Add the following:
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▪
800 HAZARDOUS DRUGS—
HANDLING IN HEALTHCARE SETTINGS
1. INTRODUCTION
1.1 Organization
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The sections in this general chapter are organized to facilitate the practitioner’s
understanding of the fundamental quality practices for preparing hazardous drugs
(HDs). The chapter is divided into the following main sections:
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1. Introduction
2. List of HDs
3. Types of Exposure
4. Responsibilities of Personnel Handling HDs
5. Facility Design and Engineering Controls
6. Personal Protective Equipment
7. Hazard Communication Program
8. Training for Compounding Personnel
9. Receiving
10. Transporting
11. Dispensing HD Dosage Forms Not Requiring Alteration
12. Compounding HD Dosage Forms
13. Protection When Administering HDs
14. Cleaning: Deactivation, Decontamination, Cleaning, and Disinfection
15. Spill Control
16. Disposal
17. Environmental Quality and Control
18. Documentation
19. Medical Surveillance
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Appendices
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a.
b.
c.
d.
e.
f.
g.
Acronyms and Definitions
Suggested Standard Operating Procedures
Types of Biological Safety Cabinets
Best Practices for Handling HDs
Examples for Design of Hazardous Drug Compounding Areas
Requirements for Personal Protective Equipment
Bibliography
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1.2 Objective
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The objective of this chapter is to protect personnel and the environment when
handling HDs. This includes but is not limited to receipt, storage, mixing, preparing,
compounding, dispensing, administering, disposing, and otherwise altering, counting,
crushing, or pouring HDs, and includes both sterile and nonsterile products and
preparations. The standards in this chapter apply to all personnel who compound HDs
preparations and all places where HDs are prepared (e.g., pharmacies, hospitals and
other healthcare institutions, patient treatment clinics, physicians’ practice facilities,
veterinarians’ offices) and other locations and facilities in which HDs are stored,
transported, and administered. Persons who compound HDs include but are not limited
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to pharmacists, nurses, pharmacy technicians, physicians, physician assistants,
veterinarians, and veterinary technicians.
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1.3 Overview
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There is no acceptable level of personnel exposure to HDs. The processes listed in
this chapter are intended to provide containment of HDs to as low a limit as reasonably
achievable (ALARA). HDs shall be compounded in proper engineering controls, as
defined in this chapter. Entities and personnel involved in compounding HDs shall be
compliant with the appropriate USP General Notices and Requirements, general
chapters, and monographs pertaining to compounding. These include but are not limited
to 795 Pharmaceutical Compounding—Nonsterile Preparations, 797
Pharmaceutical Compounding—Sterile Preparations, and 1163 Quality Assurance in
Pharmaceutical Compounding.
In addition to these USP general chapters, the following documents (or their
successors) are best practice. Where conflicts exist, the most stringent requirements
prevail.
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 OSHA Hazard Communication: OSHA Standards
(http://www.osha.gov/dsg/hazcom/standards.html)
 OSHA Technical Manual (OTM). Section VI: Chapter 2: Controlling Occupational
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Exposure to Hazardous Drugs
(http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html)
NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other
Hazardous Drugs in Health Care Settings (NIOSH Publication Number 2004165) (http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165sum.pdf)
NIOSH List of Antineoplastics and Other Hazardous Drugs in Healthcare Settings
2012 (NIOSH Publication Number 2012-150)
(http://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf)
Workplace Solutions: Personal Protective Equipment for Health Care Workers
Who Work With Hazardous Drugs (NIOSH Publication Number 2009-106)
(http://www.cdc.gov/niosh/docs/wp-solutions/2009-106/pdfs/2009-106.pdf)
Workplace Solutions: Safe Handling of Hazardous Drugs for Veterinary
Healthcare Workers (NIOSH Publication Number 2010-150)
(http://www.cdc.gov/niosh/docs/wp-solutions/2010-150/pdfs/2010-150.pdf)
Workplace Solutions: Medical Surveillance for Healthcare Workers Exposed to
Hazardous Drugs (NIOSH Publication Number 2013-103)
(http://www.cdc.gov/niosh/docs/wp-solutions/2013-103/pdfs/2013-103.pdf)
ASHP Guidelines on Compounding Sterile Preparations (2013)
(http://www.ashp.org/DocLibrary/BestPractices/PrepGdlCSP.aspx)
ASHP Guidelines on Handling Hazardous Drugs (2006)
(http://www.ashp.org/s_ashp/docs/files/BP07/Prep_Gdl_HazDrugs.pdf)
Oncology Nursing Society: Safe Handling of Hazardous Drugs (Second Edition)
(https://www.ons.org/products/safe-handling-hazardous-drugs-second-edition)
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An entity compounding HDs shall have a comprehensive approach to prevent worker
and environmental exposure. The entity’s safety and health program shall include but is
not limited to:
Engineering controls (including primary, secondary, and supplemental)
Competent personnel
Robust work practices
Availability of appropriate Personnel Protection Equipment (PPE), such as gloves
tested to the American Society for Testing and Materials (ASTM) standard for
HD permeability, gowns made of material tested for HD permeability or with
evidence of reduced permeability, and eye and respiratory protection
 Policies for the use of PPE and employee compliance with PPE use and policies
 Medical surveillance program
 Policies for HD waste segregation and disposal
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All personnel who handle HDs shall be responsible for understanding these
fundamental practices and precautions and for continually evaluating these procedures
and the quality of final HDs to prevent harm to patients or personnel and to prevent
contamination of the environment. Compounding personnel shall be responsible for
safely preparing and handling HDs. Table 1 describes the ISO classified air
environment for handling HDs and Table 2 describes the types of devices for
compounding HDs.
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Table 1. ISO Classification of Particulate Matter in Room Aira,b
Class Name
Particle Count
ISO Class
U.S. FS 209E
ISO (m3)
FS 209E (ft3)
5
Class 100
3,520
100
7
Class 10,000
352,000
10,000
8
Class 100,000
3,520,000
100,000
Limits are in particulates of 0.5 µm and larger per cubic meter (current ISO) and cubic feet (former
Federal Standard No. 209E, FS 209E).
b Adapted from former Federal Standard No. 209E, General Services Administrations, Washington, DC
20407 (September 11, 1992) and ISO 14644–1:1999, Cleanrooms and associated controlled
environments—Part I: Classification of air cleanliness. For example, 3,520 particles of 0.5 µm/m3 or larger
(ISO Class 5) is equivalent to 100 particles/ft3 (Class 100) (1 m3 = 35.2 ft3).
a Table 2. Types of Devices for Compounding with HD
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Type of
Compounding
Type of Device
Containment Ventilated Enclosure (CVE) or Class I Biological Safety
Cabinets (BSC)
Nonsterile
[NOTE—Class II BSCs or Compounding Aseptic Containment Isolators
(CACIs) may be used for nonsterile compounding if they are
dedicated for nonsterile compounding; if they are used for occasional
Type of
Compounding
Type of Device
nonsterile compounding, Class II BSCs or CACIs must undergo
thorough cleaning and disinfection before being used for sterile
compounding.]
Sterile
Class II BSC or CACI
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2. LIST OF HDS
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The National Institute for Occupational Safety and Health (NIOSH) maintains a list of
antineoplastic and other HDs used in healthcare. The entity shall include all items on
the current NIOSH list and may add others not on the NIOSH list. The entity’s list shall
be reviewed at least annually and whenever a new agent or dosage form is used. If the
information provided is deemed insufficient to make an informed decision, the drug
should be considered hazardous until more information is available.
Some dosage forms defined as hazardous may not pose a significant risk of direct
occupational exposure because of their dosage formulation (e.g., coated tablets or
capsules—solid, intact medications that are administered to patients without modifying
the formulation). Uncoated tablets may present a risk of exposure from dust by skin
contact and/or inhalation when the tablets are counted. Any solid dosage form may
pose a risk if altered, such as by crushing tablets or making solutions. The entity’s
standard operating procedure (SOP) (see Appendix B) shall identify the risk mitigation
strategies for items on the entity’s list of HDs.
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3. TYPES OF EXPOSURE
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Routes of unintentional entry of HDs into the body include dermal and mucosal
absorption, inhalation, injection, and ingestion either of contaminated foodstuffs or
mouth contact with contaminated hands. Both clinical and nonclinical personnel may be
exposed to HDs when they create or use aerosols, generate dust, clean up spills, or
touch contaminated surfaces during the receipt, preparation, administration, cleaning, or
disposal of HDs.
The following list of activities may result in exposures through skin contact, inhalation,
ingestion, or injection:
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Receiving and unpacking HD orders
Counting individual oral doses and tablets from bulk containers
Crushing tablets or opening capsules to make oral liquid
Pouring oral or topical liquids from one container to another
Mixing topical dosage forms
Weighing or mixing components
Constituting or reconstituting powdered or lyophilized HDs
Withdrawing or diluting injectable HDs from parenteral containers
Expelling air from syringes filled with HDs
Expelling HDs from a syringe
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 Contacting HD residues present on drug container exteriors, work surfaces,
floors, and final drug preparations (e.g., bottles, bags, cassettes, and syringes)
 Contacting or inhaling HD residue or aerosolization from another patient’s
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medications (such as a patient in an adjacent treatment area or exposure of
visitors)
Administering HDs by various routes, including but not limited to intramuscular,
subcutaneous, intravenous (IV), epidural, intrathecal, irrigation, oral, or topical
routes
Performing certain specialized procedures (such as intraoperative intraperitoneal
HD therapy or bladder instillation) in surgical and procedural areas
Generating aerosols during the administration of HDs, such as by direct IV push
or by IV infusion
Priming the IV set with an HD-containing solution
Handling body fluids or body-fluid-contaminated clothing, dressings, linens, and
other materials
Handling contaminated wastes generated at any step of the preparation,
dispensing, or administration process
Deactivating, decontaminating, cleaning, and disinfecting areas contaminated or
suspected of contamination with HDs
Maintenance activities for potentially contaminated equipment and devices
Spill generation, management, and subsequent disposal of spill clean-up
materials
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4. RESPONSIBILITIES OF PERSONNEL HANDLING HDS
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Each entity shall have a compounding supervisor who is the designated individual
responsible for developing and implementing appropriate procedures; overseeing facility
compliance with this chapter and other applicable laws, regulations, and standards;
ensuring competency of personnel; and assuring environmental control of the
compounding areas. The compounding supervisor shall also be responsible for the
continuous monitoring of the facility and compounded sterile preparations (CSPs),
including reports of all testing from all contractors and laboratories on facilities, CSPs,
and/or their components.
All personnel involved with mixing, compounding, and otherwise handling HDs shall be
responsible for compounding HDs of acceptable strength, quality, and purity and in
accordance with a prescription or medication order from a licensed prescriber.
Compounding personnel shall be responsible for dispensing the finished preparation
with appropriate packaging and labeling in compliance with the requirements and
recommendations established by the applicable federal, state, and local agencies,
including state boards of pharmacy, Occupational Safety and Health Administration
(OSHA), NIOSH, Environmental Protection Agency (EPA), and other organizations
(e.g., accrediting organizations, where appropriate). Individuals who are engaged in HD
compounding shall be competent in HD compounding and should continually expand
their compounding knowledge by participating in seminars, training programs, and/or
studying appropriate literature. They shall be knowledgeable in the contents of chapters
795 , 797 , and 1163 , other applicable USP chapters and General Notices and
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Requirements, and applicable federal and state laws, regulations, and guidelines.
Personnel who transport, compound, or administer HDs shall document training
according to OSHA standards (see OSHA Standard 1910.120 Hazardous Waste
Operations and Emergency Response) and other applicable laws and regulations.
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5. FACILITY DESIGN AND ENGINEERING CONTROLS
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5.1 General Guidance
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Facilities as described in this chapter for both nonsterile and sterile HD compounding
are in addition to the requirements to chapters 795 and 797 .
HDs shall be handled under conditions that promote patient safety, worker safety,
environmental protection, and infection prevention. Manipulation of HDs requires
appropriate administrative controls, PPE, engineering and environmental controls, and
work practices.
Access to areas where HDs are stored and prepared shall be restricted to authorized
staff to protect persons not involved in HD handling. The location of the HD
compounding area shall be located away from break rooms and refreshment areas for
staff, patients, or visitors to reduce risk of exposure. Signs designating the hazard shall
be prominently displayed before entry into the HD area.
Separate designated areas shall be available for (see Appendix D):
 Unpacking HDs
 Nonsterile HD compounding (if performed by the entity)
 Sterile HD compounding (if performed by the entity)
Designated HD handling areas shall be segregated from non-HD areas. Unpacking
HDs from external shipping containers shall not occur in an area used for sterile
compounding.
Storage of antineoplastic HDs shall be separate from storage of non-HDs. Storage of
non-antineoplastic HDs shall be separate from storage of non-HDs, unless only coated,
final-manufactured dosage forms are clearly labeled as HDs and safety strategies are
included in the entity’s SOPs (see Appendix B).
HDs shall not be stored, unpacked, compounded, or otherwise manipulated in an area
that is positive pressure relative to the surrounding areas. A laminar air flow workbench
(LAFW) or compounding aseptic isolator (CAI) shall not be used for the compounding of
an HD.
A BSC or CACI used for the preparation of HDs shall not be used for the preparation
of a non-HD unless the non-HD preparation is placed into a protective outer wrapper
before removal from the Containment Primary Engineering Control (C-PEC) and is
labeled to require PPE handling precautions. When asepsis is not required, a Class I
BSC, CVE, or an isolator intended for containment applications may be sufficient. A
Class II BSC may be used if it is dedicated for nonsterile preparations. For occasional
nonsterile HD compounding, a C-PEC used for sterile compounding may be used but
shall be thoroughly cleaned and disinfected before resuming sterile compounding in that
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C-PEC. HDs intended to be sterile shall be prepared in a dedicated Class II BSC or
CACI and shall follow aseptic practices specified in chapter 797 .
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5.2 Storage of HDs
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All HD storage areas and containers, regardless of the formulation, shall be labeled as
such to prevent improper handling.
Unless the HDs already exist in their final unit dose or unit-of-use packaging, HDs shall
be stored separately from other inventory in a manner to prevent contamination and
personnel exposure, which includes storage in a negative pressure room with at least
12 air changes per hour (ACPH). Depending upon pharmacy design, HD storage within
the HD buffer area can fulfill this storage criterion.
Refrigerated HDs shall be stored in a dedicated refrigerator in the HD storage room,
buffer room, or containment segregated compounding area (C-SCA). In a containment
secondary engineering control (C-SEC) used for sterile preparations, an exhaust
located adjacent to the refrigerator’s compressor and behind the refrigerator should be
considered.
HDs shall be stored at or below eye level, in containers that minimize the risk of
breakage and leakage, and shall not be stored on the floor. Areas prone to specific
types of natural disasters (e.g., earthquakes) shall ensure that storage meets applicable
safety precautions, such as secure shelves with raised front lips. Storage of sterile and
nonsterile HDs may be intermingled. HD storage in a sterile compounding buffer area
shall be limited to those used for sterile compounding (see chapter 797 ).
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5.3 Engineering Controls
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5.3.1 BACKGROUND
HDs shall be prepared only under conditions that protect the healthcare workers and
other personnel in the preparation and storage areas. Within this chapter, engineering
controls are divided into three categories representing primary, secondary, and
supplementary levels of control (see Appendix A and Appendix C for more details). CPECs provide the environment at the point of use and are integrated into the C-SEC
(i.e., room). The C-SEC supports the C-PEC. Supplemental engineering controls are
adjunct controls [e.g., closed-system drug-transfer device (CSTD)] used in conjunction
with primary and secondary control strategies.
HDs that require alteration shall be manipulated (mixed, diluted, compounded, and
others) in a C-PEC in an area that is physically separated from other preparation areas,
that is under negative pressure, and has at least 12 ACPH. Additional criteria are listed
below.
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5.3.2 CONTAINMENT PRIMARY ENGINGEERING CONTROLS
All C-PECs shall be externally vented and place in a restricted access segregated
room which has a minimum negative pressure of 0.01 inches of water column.
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5.3.3 CONTAINMENT SECONDARY ENGINGEERING CONTROLS
HD compounding activities must occur within a C-SEC where any C-PEC shall be
vented to the outside air through high efficiency particle air (HEPA) filtration. For both
sterile and nonsterile HD compounding, a sink shall be available for hand washing as
well as emergency access to water for removal of hazardous substances from eyes and
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skin; it shall not be within an ISO Class 7 buffer area. An eyewash station or other
emergency or safety precautions that meet applicable laws and regulations shall be
readily available; however, care must be taken to locate them in areas where their
presence will not interfere with required ISO classifications.
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5.4 Nonsterile HD Compounding
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5.4.1 C-PEC FOR NONSTERILE HD COMPOUNDING
Nonsterile HD compounding shall be performed in a C-PEC that provides personnel
and environmental protection, such as a Class I BSC or CVE. Unidirectional airflow
within the C-PEC is not required, because the critical environment for nonsterile
compounding does not require an ISO-classified environment. The C-PEC used for
nonsterile compounding shall be externally vented. A C-PEC is not required if
manipulations are limited to handling of intact final manufactured products (e.g., coated
tablets or capsules) that do not produce aerosols or gasses or involve manipulation of
powders. A Class II BSC or a CACI may be used if it is dedicated for use with nonsterile
compounding or if it undergoes thorough cleaning and disinfection procedures after
nonsterile compounding and before re-use for sterile compounding.
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5.4.2 C-SEC FOR NONSTERILE HD COMPOUNDING
Nonsterile compounding shall be performed in an area that meets the requirements of
chapter 795 and the requirements of this chapter. The C-PEC shall be placed in a
room that is physically separated (i.e., a different room from other preparation areas)
but does not need to be ISO 7 nor have HEPA-filtered air.
The C-SEC shall meet the following requirements:
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 Minimum of 12 ACPH
 Maintained at a negative pressure of at least 0.01 inches of water column relative
to all adjacent spaces (rooms, above ceiling, and corridors). [
NOTE—Although negative pressure within the HD buffer area is important, the
negative pressure should not be so strong that it induces environmental
contamination migration into the buffer area from unclassified adjacent spaces.]
 Due to the difficulty of cleaning HD contamination from surfaces, the architectural
finish requirements (e.g., smooth, seamless, impervious surfaces) prescribed in
chapter 797 also apply to nonsterile compounding areas (see Table 3).
Table 3. Acceptable Configuration for Nonsterile HD Compounding
Function
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C-PEC
C-SEC
Airflow
Maximum BUD
Nonsterile compounding Any C-PEC C-SEC 12 ACPH (exhaust) As listed in
See Appendix D for best practices for compounding nonsterile HDs.
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5.5 Sterile HD Compounding
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5.5.1 C-PEC FOR STERILE HD COMPOUNDING
795
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Sterile HD compounding shall be performed in a C-PEC that provides an ISO Class 5
critical area and shall be used in conjunction with aseptic practices specified for the
appropriate risk levels defined in chapter 797 .
The airflow in the C-PEC shall be unidirectional (laminar flow), and because of the
particle collection of the filter, the “first air” at the face of the filter is, for the purposes of
aseptic compounding, free from airborne particulate contamination. HEPA-filtered air
shall be supplied in critical areas (ISO Class 5) at a velocity sufficient to sweep particles
away from the compounding area and to maintain unidirectional airflow during
operations. Proper design and control prevents turbulence and stagnant air in the
critical area. In situ air pattern analysis via smoke studies shall be conducted at least
every 6 months at the critical area to demonstrate unidirectional airflow and to
demonstrate the sweeping action over and away from the product under dynamic
conditions. C-PECs include Class II and III BSCs, CACIs, or any other device intended
to create an aseptic work environment or containment (e.g., a robot system enclosure).
Class II BSC types A2, B1, or B2 are all acceptable; however, for most known HDs,
type A2 cabinets offer a simple and reliable integration with the ventilation and
pressurization requirements of the secondary engineering control. Class II type B2
BSCs are typically reserved for use with highly volatile components.
Sterile compounding shall be performed in an area that meets the requirements of
797 and the requirements of this chapter. Three C-PEC/C-SEC configurations are
acceptable for sterile-to-sterile compounding (e.g., low-risk level, and medium-risk level
CSPs). Two C-PEC/C-SEC configurations are acceptable for nonsterile-to-sterile
compounding (e.g., high-risk level CSPs). C-PEC placement in a C-SEC that meets ISO
Class 7 is preferred. If a C-PEC is placed in a room with air quality worse than ISO
class 7, the BUD of all CSPs prepared in that area may need to be limited to 12 h,
depending on the type of C-PEC used (see Table 4).
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Table 4. Acceptable Configurations for Sterile-to-Sterile HD Compounding
Configuration
1
Function
Compounding sterile HD in
a cleanroom
CPEC
Airflow
Maximum
BUD
BSC
30 ACPH
or
ISO 7
(HEPA
CACI Cleanroom supply)
As listed in
797
12 ACPH
(exhaust)
As listed in
797
C-SEC
Compounding sterile HD in
a CACI that meets the
requirements listed in 797
2
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CACI C-SCA
Compounding low- or
medium-risk sterile HDs in a
BSC. [NOTE—This
configuration is not
acceptable for high-risk
12 ACPH
3
sterile HD compounding.]
BSC C-SCA
(exhaust)
See Appendix D for best practices for compounding sterile HDs.
12 hours
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5.5.2 CONFIGURATION 1 FOR STERILE COMPOUNDING
The C-PEC shall be placed in an ISO Class 7 buffer area that is physically separated
(i.e., a different room from other preparation areas) and meets the following
requirements:
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 Minimum of 30 ACPH of HEPA-filtered supply air
 Buffer area shall be maintained at a negative pressure of at least 0.01 inches of
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water column relative to all adjacent spaces (rooms, above ceiling, and
corridors). [
NOTE—Although negative pressure within the HD buffer area is important, the
negative pressure should not be so strong that it induces environmental
contamination migration into the buffer area from unclassified adjacent spaces.]
 Incorporate the remaining relevant design criteria specified in chapter 797
Rooms through which entry into the negative-pressure buffer room occurs (anteroom
or non-HD buffer room) shall be positive-pressure ISO Class 7 or better so that inward
air migration is of equal cleanliness classification to that in the negative-pressure buffer
area. A pressure indicator shall be installed that can be readily monitored for correct
room pressurization.
Because the anteroom leading into the HD buffer room plays an important function in
terms of total contamination control within the buffer room, the anteroom must be
constructed using principles similar to those used in non-HD sterile compounding.
These include:
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 Minimum of 30 ACPH of HEPA-filtered supply air
 Anteroom shall be maintained at a minimum positive pressure of 0.02 inches of
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Although not a recommended facility design, if the negative pressure HD buffer room
is entered though the positive-pressure, non-HD buffer room, additional facility criteria
are required:
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water column relative to all adjacent unclassified spaces
 The anteroom shall be maintained at a minimum positive pressure of at least
0.01 inches of water column relative to the HD buffer room
 The anteroom should incorporate a visual line of demarcation to differentiate the
“clean” side from the “dirty” side of the anteroom to support the gowning
requirements prescribed in 797
 A hand-washing sink shall be placed within the anteroom on the "clean" side of
the line of demarcation
 An area used for garbing/degarbing shall be defined by a line of demarcation
within the negative-pressure buffer room
 A method to transport HDs into the negative-pressure buffer room and to remove
CSPs and waste from the negative-pressure buffer room shall be used to
minimize the spread of HD contamination. This may be accomplished by use of
a pass-through between the negative-pressure buffer room and adjacent space.
The pass-through shall be included in the required semi-annual facility
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certification to ensure that particles are not compromising the air quality of the
negative-pressure buffer room. Other methods of containment (such as sealed
containers) may be used if the entity can demonstrate HD containment and
appropriate environmental control.
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HD CSPs prepared in this cleanroom configuration may use the BUDs listed in chapter
797 , based on risk levels and storage temperature.
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5.5.3 CONFIGURATION 2 FOR STERILE COMPOUNDING
A CACI that meets the requirements listed in chapter 797 may be placed in a CSCA that is physically separated (i.e., a different room from other preparation areas) but
does not need to be ISO 7 nor have HEPA-filtered air. The C-SCA shall meet the
following requirements:
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 Minimum of 12 ACPH
 Maintained at a negative pressure of at least 0.01 inches of water column relative
to all adjacent spaces (rooms, above ceiling, and corridors). [
NOTE—Although negative pressure within the HD buffer area is important, the
negative pressure should not be so strong that it induces environmental
contamination migration into the buffer area from unclassified adjacent spaces.]
 Incorporate the remaining relevant design criteria specified in chapter 797
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HD CSPs compounded in this CACI/C-SCA configuration may use the BUDs listed in
chapter 797 based on risk levels and storage temperature.
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5.5.4 CONFIGURATION 3 FOR STERILE COMPOUNDING
This configuration shall not be used for high-risk, sterile HD compounding. A BSC or
CACI that does not meet the requirements in 797 may be placed in a C-SCA that is
physically separated (i.e., a different room from other preparation areas) but does not
need to be ISO Class 7 nor have HEPA-filtered air. The C-SCA shall meet the following
requirements:
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 Minimum of 12 ACPH
 Maintained at a negative pressure of at least 0.01 inches of water column relative
to all adjacent spaces (rooms, above ceiling, and corridors). [
NOTE—Although negative pressure within the HD buffer area is important, the
negative pressure should not be so strong that it induces environmental
contamination migration into the buffer area from unclassified adjacent spaces.]
 Incorporate the remaining relevant design criteria specified in chapter 797
HD CSPs compounded in this configuration shall not exceed a BUD of 12 hours.
5.6 Nonsterile and Sterile Compounding
For entities that compound both nonsterile and sterile HDs, the respective C-PECs
shall be placed in segregated rooms separate from each other, unless those C-PECs
used for nonsterile compounding are sufficiently effective that the room can
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continuously maintain ISO 7 classification throughout the nonsterile compounding
activity.
5.6.1 FACULTY DESIGN
See Appendix E for example designs of HD compounding areas.
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5.6.2 ENGINEERING CONTROL OPERATION
The C-PEC shall operate continuously. If it is necessary to power off the unit for repair
or moving, clean the C-PEC (see 14. Cleaning section) and protect the unit by
appropriately covering it per the manufacturer’s recommendations. Once the C-PEC
can be powered on, disinfect all interior surfaces before resuming compounding, and
wait the time required for the system to purge as listed in the manufacturer’s
instructions. Activities of handling HDs shall be immediately suspended if there is an
interruption of operation to the C-PEC or the C-SEC, such as loss of room
pressurization due to loss of power.
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5.7 Containment Supplemental Engineering Controls
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Some CSTDs have been shown to limit the potential for generating aerosols during
compounding; however, there is no certainty that all CSTDs will perform adequately.
There does not yet exist a universal performance protocol by which all CSTDs are
evaluated for containment. Until such a protocol is developed and adopted, users
should carefully evaluate the performance claims associated with available CSTDs.
When a widely-accepted protocol for CSTD performance evaluation is developed, users
are encouraged to focus upon CSTD manufacturers that subject their CSTD devices to
independent evaluation under this protocol. CSTDs used as a supplemental control for
compounding shall be used inside a C-PEC. CSTDs should be used when
compounding HDs when the dosage form allows. CSTDs shall be used when
administering HDs when the dosage form allows.
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6. PERSONAL PROTECTIVE EQUIPMENT
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PPE provides worker protection by supplementing engineering controls to reduce
exposure to HD aerosols and drug residue. When performing a task when engineering
controls are not generally available, such as cleaning a spill, additional PPE may be
required.
Appropriate PPE shall be worn when handling HDs. See Appendix F for requirements
for PPEs based on function:
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Receiving intact supplies (remote from the compounding area)
Receiving suspected/broken supplies
Transporting intact supplies or compounded HDs
Receiving intact supplies in the compounding area
Stocking and inventory control of the compounding area
Nonsterile compounding
Sterile compounding
Collecting and disposing compounding waste
Administering
Routine cleaning
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 Collecting and disposing patient waste
 Managing spills
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The garbing and gloving requirements listed here shall be used for compounding any
HD (nonsterile and sterile) in any setting and when using any and all C-PECs.
The SOP manual (see Appendix B) of the compounding facility shall specifically
describe the appropriate PPE to be worn based on a written safety and health program.
PPE, in addition to those listed below, may be used to reduce exposure or to protect
workers from contamination.
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6.1 Gloves
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Gloves used shall be labeled as ASTM-tested chemotherapy gloves; this information is
available on the box or from the manufacturer.
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 Use powder-free gloves, because the powder can contaminate the work area
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and can adsorb and retain HDs.
 Inspect gloves for physical defects before use. Do not use gloves with pin-holes
or weak spots.
 Wear two pairs of ASTM-tested chemotherapy gloves when compounding,
administering, managing a spill, and disposing of HDs. For sterile preparations,
the outer glove shall be sterile. Wear the inner glove under the gown cuff and
the outer glove over the cuff. Place gloves with long cuffs over the cuff of the
gown to protect the wrist and forearm.
The following work practices shall be followed:
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 Hand hygiene shall be performed in accordance with the CDC Guidelines for
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6.2 Gowns
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Disposable gowns that protect the worker from spills and splashes of HDs and waste
materials and that have been tested to resist permeability by HDs shall be worn when
handling HDs. Selection of gowns shall be based on the HDs used.
Disposable gowns made of polyethylene-coated polypropylene or other laminate
materials offer better protection than those of noncoated materials. Gowns shall close in
the back (no open front), have long sleeves, and have closed cuffs that are elastic or
knit. Gowns shall not have seams or closures that could allow drugs to pass through.
Hand Hygiene in Healthcare Settings or WHO Guidelines on Hand Hygiene in
Health Care before donning gloves and immediately after removal of the gloves.
 When working within a CACI, the outer glove (over the isolator glove) shall be a
sterile, powder-free, ASTM-tested chemotherapy glove. Maintain an additional
supply of gloves near the CACI to don when needed during transfer of materials
in or out of the CACI antechamber.
 Change gloves every 30 min or when torn, punctured, or contaminated. Carefully
remove and discard them immediately in an approved HD waste container
inside the C-PEC or contain them in a sealable bag for discarding outside the
C-PEC.
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Cloth laboratory coats, surgical scrubs, isolation gowns, or other absorbent materials
are not appropriate outer wear when handling HDs, because they permit the permeation
of HDs and can hold spilled drugs against the skin and increase exposure.
The following work practices shall be followed:
 Wear gowns whenever there is a possibility of HD contact with skin or clothing
during compounding or administration of HDs. Clothing may retain HD residue
from contact, and personnel may transfer this residue to patients, family
members, staff, or other surfaces. Washing of non-disposable clothing
contaminated with HD residue may transfer drug residue to other clothing.
 Do not wear gowns outside the compounding or administration area if they have
been worn in the HD compounding area to avoid spreading drug contamination
to other areas and exposing unprotected workers.
 Adhere to the time limit that the manufacturer lists for permeation of the gown. If
no permeation information is available for the gowns used, change them every
2–3 hours or immediately after a spill or splash.
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6.3 Head, Hair, Shoe, and Sleeve Covers
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Head and hair (including beard and moustache, if applicable) and shoe covers shall be
worn to reduce the possibility of particulate or microbial contamination in HD
compounding areas. Hair, head, and shoe covers provide additional protection from
contact with HD residue on surfaces and floors.
The following work practices shall be followed:
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 Do not wear shoe covers outside the HD compounding areas to avoid spreading
drug contamination to other areas and possibly exposing unprotected workers.
 If sleeve covers are used, they shall be constructed of coated materials to
provide additional protection for the areas of the arms that may come in contact
with HDs within BSCs. Use disposable sleeve covers to protect the wrist area,
and remove the covers carefully after the task is complete. Discard sleeve
covers after one use, and contain and dispose of them as trace contaminated or
trace chemotherapy waste.
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6.4 Eye and Face Protection
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Appropriate eye and face protection shall be worn when handling HDs outside an
engineering control. A full-facepiece respirator also provides eye and face protection.
Goggles shall be used when eye protection is needed; eye glasses alone or safety
glasses with side shields do not provide adequate protection to the eyes from splashes.
Many HDs are irritating to eyes and mucous membranes. Follow these work practices
when using eye and face protection:
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 Use eye and face protection when manipulating an HD outside of a C-PEC (e.g.,
in the surgical suite), working at or above eye level, cleaning a C-PEC, or
cleaning a spill.
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 Use face shields in combination with goggles to provide a full range of protection
against splashes to the face and eyes. Face shields alone do not provide full
eye and face protection.
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6.5 Respiratory Protection
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For most activities requiring respiratory protection, an NIOSH-certified N95 or more
protective respirator is sufficient to protect against airborne particles; however, these
respirators offer no protection against gases and vapors and little protection against
direct liquid splashes (see CDC’s Respirator Trusted-Source Information at
http://www.cdc.gov/niosh/npptl/topics/respirators/disp_part/RespSource3healthcare.html
#e). Surgical masks do not provide respiratory protection from drug exposure and
should not be used to compound or administer drugs. A surgical N95 respirator provides
the respiratory protection of an N95 respirator and the splash protection provided by a
surgical mask.
Personnel unpacking HDs that are not contained in plastic should wear an elastomeric
half-mask with a multi-gas cartridge and P100-filter. If the type of drug can be better
defined, then a more targeted cartridge could be used.
Fit test the respirator and train workers to use respiratory protection. Follow all
requirements in the OSHA respiratory protection standard (29 CFR 1910.134)
(http://www.osha.gov/SLTC/etools/respiratory/index.html). An appropriate full-facepiece,
chemical cartridge-type respirator shall be worn when attending to HD spills larger than
what can be contained with a spill kit, or when there is known or suspected airborne
exposure to powders or vapors.
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6.6 Disposal of Used PPE
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Consider all PPE worn when handling HDs as being contaminated with, at a minimum,
trace quantity of HDs. Unless local regulations prohibit, these items shall be incinerated
at a regulated medical waste incinerator. They should not be placed into red bag or red
sharps containers.
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7. HAZARD COMMUNICATION PROGRAM
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OSHA requires each workplace to have a written Hazard Communication Program.
The Hazardous Communication Standard (HCS) (see
https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p
_id=10099) applies to all workers. Employers are required to establish policies and
procedures to ensure worker safety in all aspects of the distribution of these drugs and
chemicals.
The HCS requires each employer to provide training, proper labeling, and Safety Data
Sheets (SDS), based on the Globally Harmonized System of Classification of Labeling
of Chemicals (GHS).
Elements of the plan shall include:
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 A written plan that describes how the standard will be implemented.
 All containers of hazardous chemicals shall be labeled, tagged, or marked with
the identity of the material and appropriate hazard warnings.
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 Chemical manufacturers and importers are required to obtain or develop an SDS
for each hazardous chemical they produce or import. Distributors are
responsible for ensuring that their customers are provided a copy of these
SDSs. Employers shall have an SDS for each hazardous chemical they use.
 Each employee who may be exposed to hazardous chemicals when working
shall be provided information and training before initial assignment to work with
a hazardous chemical, and whenever the hazard changes.
Employers shall maintain in the workplace copies of the required SDSs for each
hazardous chemical and shall ensure that the SDSs are readily accessible to
employees during each work shift and when they are in their work areas.
8. TRAINING FOR COMPOUNDING PERSONNEL
Administrative controls include establishment of policies and procedures, a robust
training program, and implementation of appropriate work practices. All personnel who
compound HDs shall be fully trained in the storage, handling, and disposal of these
materials. This training shall occur before preparing or handling hazardous
preparations, and the effectiveness of the training shall be verified by testing specific
HD preparation techniques. All training shall be documented, and personnel
competency shall be reassessed and documented at least every 12 months, or
whenever a new HD is used or a new or significant change in process or SOP occurs.
Personnel who compound sterile hazardous preparations shall be trained in aseptic
and negative-pressure techniques. Steps in the training procedure (for both nonsterile
and sterile compounding) include the following:
 All compounders involved in hazardous compounding shall read and become
familiar with this chapter. They shall be knowledgeable with the contents of
chapters 795 , 797 , and 1163 ; specific publications of NIOSH Alert:
Preventing Occupational Exposures to Antineoplastic and Other Hazardous
Drugs in Health Care Settings, Medical Surveillance for Healthcare Workers
Exposed to Hazardous Drugs, OSHA Technical Manual, and Controlling
Occupational Exposure to Hazardous Drugs; and other relevant publications,
including how to read and interpret SDSs.
 All compounders shall read and become familiar with each of the entity’s SOPs
(see Appendix B) related to hazardous compounding, including those involving
the facility, equipment, PPE, compounding processes, hazardous waste
disposal, evaluation, packaging, storage, spill containment, decontamination,
and dispensing or delivery.
 The compounding supervisor or designee shall demonstrate the procedures for
the compounder and shall observe and guide the employee throughout the
training process. The compounder shall then repeat the procedure without any
assistance from, but under the direct supervision of, the compounding
supervisor or designee.
 The compounding supervisor shall routinely monitor the work of the compounder
and ensure that the compounder is following appropriate HD precautions and
that the compounder’s calculations and work are accurate and adequately
performed. The monitoring shall be documented as part of the entity’s
competency assessment program.
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The training shall include at least the following:
 Didactic overview of types of HDs and their risks, including carcinogenic,
genotoxic, teratogenic, organ toxicity, and adverse reproductive properties
 Review of the entity’s policies and procedures for personnel who handle HDs,
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including the process to request alternative duty
Ordering, receiving, and stocking of HDs
Proper hand hygiene
Use of PPE
Use of C-PECs and other equipment and devices
Negative-pressure techniques when using C-PECs
Safe aseptic practices, if applicable
Containment, clean-up, and disposal procedures for normal use and for
breakage and spills
Treatment of personal contact and any unintended exposure
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9. RECEIVING
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The compounding supervisor shall ensure that the products and components received
are consistent with principles of Good Distribution Practices. HDs should be received
from the supplier sealed in impervious plastic to segregate them from other drugs, to
allow for safety in the receiving and internal transfer process, and should be
immediately delivered to the C-SEC. HDs shall only be stored in areas with the
ventilation controls described in this chapter.
Receiving personnel shall be trained per the entity’s SOP (see Appendix B). Training
shall be documented.
PPE, including ASTM-tested, powder-free chemotherapy gloves, shall be worn when
handling HDs (see Appendix F for PPE requirements). A spill kit shall be accessible in
the receiving area.
The entity shall enforce policies that include a tiered approach, including:
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 Visual examination of the shipping container for signs of damage or breakage
- If shipping containers appear undamaged, they shall be handled per
entity-defined procedures.
- If shipping containers appear damaged, the following additional action is
required:
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o
Don appropriate PPE.
Enact facility policies to determine whether the package will be
sealed and returned to the supplier or whether it will be opened.
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o
If the intent is to return the package to the supplier, enclose the
package in an impervious container, label the outside container as
“Hazardous”, and contact the supplier for instructions.
Transportation by common carrier will require compliance with
Hazardous Materials Limited Quantity Marking Requirements (see
http://www.ecfr.gov/cgi-bin/textidx?rgn=div8&node=49:2.1.1.3.8.4.25.11).
- If the damaged package must be opened, a Class I (see
Appendix C) containment device used for nonsterile HD
compounding shall be used.
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- Place a plastic-backed preparation mat on the work surface of the
Class I device.
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- Open the package and remove usable items.
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

Wipe the outside of the usable items with a disposable
wipe.
Enclose the damaged item(s) in an impervious container,
label the outside container as “Hazardous”, and contact
the supplier for instructions.
- Clean the Class I device (see 14. Cleaning section), and discard
the mat and cleaning disposables as hazardous waste.
Damaged packages or shipping cartons shall be considered spills that shall be
reported to the compounding supervisor and conform to other entity-defined reporting
processes. Clean-up shall comply with established SOPs (see Appendix B).
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10. TRANSPORTING
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10.1 Transporting from Receiving to the Storage/Compounding Area
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Personnel transporting HDs shall be trained and their competency documented. HDs
require safeguards to maintain the integrity of the HD and to minimize the potential for
breakage or spill exposure of these products to the environment and to personnel who
may come in contact with them.
Drugs that have been identified as requiring HD handling precautions shall be clearly
labeled at all times during their transport and use. HDs shall be transported in closed
containers that minimize the risk of breakage or leakage.
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10.2 Transporting from Compounding to Patient Areas Within the Healthcare
Entity
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The entity shall establish SOPs (see Appendix B) pertaining to packaging, transport,
and handling of HDs. The SOPs shall address prevention of accidental exposures or
spills, personnel training to respond to exposure, and use of a spill kit. Examples of
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special exposure-reducing strategies include Luer lock syringes and connections,
syringe caps, the capping of container ports, sealed impervious plastic bags, impactresistant and/or water-tight containers, and cautionary labeling. HDs shall not be
transported in pneumatic tubes because of potential breakage and contamination.
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10.3 Transporting from Compounding to Outside the Healthcare Entity
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When HDs are distributed to locations outside the premises in which they are
compounded, compounding personnel shall select packing containers and materials
that are expected to maintain physical integrity, stability, and sterility (if needed) of HDs
during transit. Packing shall be selected that simultaneously protects HDs from damage,
leakage, contamination, and degradation and protects personnel who transport packed
HDs. The entity’s approved SOPs (see Appendix B) shall specifically describe
appropriate packing containers and insulating and packing materials, based on
information from product specifications, vendors, and the experience of the
compounding personnel. Written instructions that clearly explain how to safely open
containers of packed HDs shall be provided to patients and other recipients. Transport
of HDs shall be labeled, stored, and handled in accordance with applicable federal,
state, and local regulations.
Compounding personnel shall ascertain that temperatures of HDs during transit by the
selected mode do not deviate from the warmest temperature specified on the storage
temperature range on HD labels (see 1079 Good Storage and Distribution Practices
for Drug Products). Compounding personnel should communicate directly with the
couriers to learn shipping durations and exposure conditions that HDs may encounter.
Refer to 795 and 797 for additional storage information.
Compounding facilities that ship HDs to patients and other recipients outside their own
premises shall ascertain or provide, whichever is appropriate, the following assurances:
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 Delivery performance of couriers to ascertain that HDs are being efficiently and
properly transported.
 Labels and accessory labeling for HDs include clearly readable BUDs, storage
instructions, disposal instructions for out-of-date units, and HD category labels
that shall be consistent with the carrier’s policies.
 Each facility, patient, or other recipient can store the HD properly; including the
use of a properly functioning refrigerator or freezer if the HD is labeled for such
storage.
11. DISPENSING HD DOSAGE FORMS NOT REQUIRING ALTERATION
HDs in unit-dose or unit-of-use packaging that do not require any further alteration
before delivery to the patient or the patient’s caregiver may be dispensed without any
further requirements for containment unless required by the manufacturer.
If the entity’s SOPs permit, non-antineoplastic HDs that require only transfer from the
manufacturer’s package to a prescription container may be dispensed without any
further requirements for containment unless required by the manufacturer. Counting of
HDs should be done carefully, and clean equipment should be dedicated for use with
these drugs.
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Tablet and capsule forms of HDs shall not be placed in automated counting machines,
which subject them to stress and may introduce powdered contaminants into the work
area. Counting coated tablets and capsules does not require a C-PEC, as long as they
are not altered or broken.
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12. COMPOUNDING HD DOSAGE FORMS
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Compounding personnel are responsible for ensuring that HDs are accurately
identified, measured, diluted, and mixed and are appropriately sterilized (when
appropriate), packaged, sealed, labeled, stored, dispensed, and distributed. These
performance responsibilities include maintaining clean conditions and providing labeling
and supplementary instructions for the proper administration of HDs.
Work practices for compounding nonsterile HD dosage forms shall include:
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 Using requirements listed in chapter 795 .
 Avoiding use of active pharmaceutical ingredients (APIs) if a suitable
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manufactured product is available and appropriate for use, e.g., using an
injection rather than a bulk powder.
Manipulation of any HDs (such as crushing tablets or opening capsules) shall be
performed carefully, within a C-PEC using appropriate PPE. Clean equipment
(such as mortars and pestles, spatulas, and others) shall be dedicated for use
with HDs. Crushing tablets or opening capsules should be avoided if possible;
liquid formulations should be used if oral solids are not appropriate for the
patient.
Handling bulk containers of liquid HDs carefully to avoid spills. These containers
shall be dispensed and maintained in sealable, impervious plastic bags or other
suitable containers to contain any inadvertent contamination.
Ensuring that processes for labeling the compound do not introduce
contamination into non-HD areas.
Dispensing in the final dose and form whenever possible.
Work practices for compounding sterile HD dosage forms shall include:
 Using requirements listed in chapter 797 .
 Avoiding the use of APIs if a suitable manufactured product is available and
appropriate for use, e.g., using an injection rather than a bulk powder.
 Appropriately preparing materials used in compounding before introduction into
the Class II BSC or the pass-through of a CACI (see chapter 797
details).
 Ensuring that processes for labeling the compound do not introduce
contamination into non-HD areas.
for
The compounding areas shall be properly cleaned after compounding activities.
13. PROTECTION WHEN ADMINISTERING HDS
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Work practices for administering HDs shall include:
 Administering drugs safely by using protective medical devices (such as
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needleless and closed systems) and techniques (such as spiking and priming of
IV tubing by pharmacy personnel inside a C-PEC, and/or priming in-line with
nondrug solutions).
Using CSTDs when administering HDs, when the dosage form allows.
Complying with hand hygiene practices before and after manipulation of the HDs.
Wearing PPE (including two pairs of ASTM-tested gloves and protective gowns)
for activities associated with drug administration—opening the outer bag,
assembling the delivery system, delivering the drug to the patient, and
disposing of all equipment used to administer drugs. Wear eye protection where
splashing is possible.
Removing outer gloves and gowns and bagging them for disposal in the
approved chemotherapy waste container at the site of drug administration.
Remembering that HDs administered in locations, such as the surgical suite,
present challenges to training and containment. Intracavitary administration of
HDs (e.g., into the bladder, peritoneal cavity, or chest cavity) frequently requires
equipment for which locking connections may not be readily available or
possible.
Ensuring that all staff members who handle HDs receive safety training that
includes recognition of HDs and appropriate spill response. HD spill kits,
containment bags, and disposal containers shall be available in all areas where
HDs are handled.
Using techniques and ancillary devices that minimize the risk of open systems
when administering HDs through unusual routes or in non-traditional locations.
The Oncology Nursing Society (ONS) Safe Handling of Hazardous Drugs publication
contains additional details that may be incorporated into SOPs (see Appendix B).
14. CLEANING: DEACTIVATION, DECONTAMINATION, CLEANING, AND
DISINFECTION
Personnel performing cleaning activities (including compounding, direct care,
environmental services, laundry, waste handling, and others) shall be protected from
inadvertent exposure to HDs.
14.1 Routine Cleaning, Decontaminating, and Waste Disposal
Work practices for environmental services and other personnel who handle HDs shall
include:
 Wearing two pairs of ASTM-tested chemotherapy gloves that are chemically
resistant to the decontamination or cleaning agents used. Consult
manufacturers’ and suppliers’ information to determine appropriateness.
 Wearing eye protection.
 Wearing face shields, if splashing is possible.
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826
14.2 Exposure to Biologic Waste from HD-Treated Patients
Follow applicable laws, regulations, guidelines, and entity policy.
827
14.3 Cleaning HD Areas
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846
The entity shall establish cleaning routines consistent with this chapter and with
recommendations from the C-PEC manufacturer. The routines shall include periodic
cleaning of all work surfaces and equipment that may become contaminated, including
administration carts and trays. Details shall be included in the entity’s SOPs (see
Appendix B), including processes, solutions and dilutions used, and documentation
requirements.
Personnel shall wear eye protection and ASTM-tested chemotherapy gloves for
deactivating, decontaminating, cleaning, and disinfecting. Gloves used shall be
chemically resistant to the cleaning agents used. Face shields shall be worn if splashing
is possible.
The choice of cleaning products shall be related to the product and preparation, time,
and application of the decontamination product, equipment used, and resistance
patterns.
The equipment used for compounding HDs shall be dedicated for HDs and shall be
chosen so that the equipment can be effectively cleaned (and sterilized, if necessary, by
steam, dry heat, or other methods). Perform cleaning in areas that are sufficiently
ventilated to prevent build-up of hazardous airborne drug concentrations and
decontamination agents. Cleaning of nonsterile compounding equipment shall not be
done when sterile compounding is underway in the same room.
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14.4 Cleaning C-PEC and Other Devices Used for Compounding HDs
848
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852
853
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856
Cleaning C-PEC, other devices and equipment, and areas used for compounding HDs
involves several steps that are discussed below:
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866
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14.4.1 DEACTIVATION
Chemical deactivation of a hazardous substance is preferred, but no single process
has been found to deactivate all currently available HDs. Deactivation shall occur when
an appropriate agent is identified. Note that alcohol is not a deactivation agent, and the
use of alcohol before deactivating and decontamination may result in the spread of
contamination rather than any actual cleaning. A multi-component deactivation system
is theoretically more efficient than a single-agent system because of the diverse nature
of HDs.
The SDSs of some HDs recommend use of sodium hypochlorite; generally, this should
be a 2% solution. Note that sodium hypochlorite will pit stainless steel surfaces;
therefore, the sodium hypochlorite must be removed with sodium thiosulfate or followed
by use of a germicidal detergent in sterile water.
14.4.1 Deactivation
14.4.2 Decontamination
14.4.3 Cleaning
14.4.4 Disinfecting
The entity’s SOPs shall include the procedure, the components and dilutions (if
applicable) used, and the documentation requirements for all four steps.
869
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14.4.2 DECONTAMINATION
Decontamination occurs by removing HD residue from surfaces, and transferring them
to a low-lint wipe, which is then contained and discarded as contaminated waste. The
amount of HD contamination introduced into the BSC or CACI may be reduced by
surface decontamination (i.e., wiping down) of HD containers. Although no wipe-down
procedures have been studied, the use of low-lint wipes moistened with alcohol, sterile
water, peroxide, or sodium hypochlorite solutions may be effective. The solvent used for
wiping vials must not alter the product label. The BSC or CACI should be
decontaminated at least weekly, any time a spill occurs, before and after certification,
voluntary interruption, or if the ventilation tool is moved.
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881
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883
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14.4.3 CLEANING
The Cleaning section in chapter 797 is appropriate for both nonsterile and sterile
HDs. The products used for cleaning shall not contaminate the compounding equipment
with substances that are toxic, volatile, corrosive, or otherwise harmful to the surface.
To clean C-PECs, refer to manufacturer’s information and appropriate references for
guidance in developing the entity’s cleaning procedures.
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890
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894
14.4.4 DISINFECTING
The products used for disinfecting shall not contaminate the compounding equipment
with substances that are toxic, volatile, corrosive, or otherwise harmful to the surface. CPECs used for compounding HDs shall be disinfected at the beginning of the workday,
between batches of compounding medications, at the beginning of each subsequent
shift (if compounding takes place over an extended period of time), routinely during
compounding, and after anytime the C-PEC has been powered off. The area under the
work tray shall be cleaned at least monthly to reduce the contamination level in the
BSCs and CACIs. Clean as much as possible before opening the area under the work
tray. When cleaning a CACI, don a respirator when opening the front of the cabinet.
895
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15. SPILL CONTROL
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911
Spills shall be contained and cleaned immediately by trained workers. Signs shall be
available to restrict access to the spill area. Only trained workers with appropriate PPE
shall manage an HD spill. All workers who may be required to clean up a spill of HDs
shall receive proper training in spill management and in the use of PPE and NIOSHcertified respirators (see 6. Personal Protective Equipment).
Policies and procedures shall be developed to prevent spills and to govern clean-up of
HD spills. Written procedures shall specify who is responsible for spill management and
shall address the size and scope of the spill. Spill kits containing all of the materials
needed to clean HDs spills shall be readily available in all areas where HDs are
routinely handled. If HDs are being prepared or administered in a non-routine area (e.g.,
home setting, unusual patient care area), a spill kit and respirator shall be available.
The circumstances and handling of spills shall be documented. Workers who are
contaminated during the spill or spill clean-up, or who have direct skin or eye contact
with HDs, require immediate treatment. Staff and nonemployees exposed to an HD spill
should also complete an incident report or exposure form and report to the designated
912
913
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931
emergency service for initial evaluation. All spill materials shall be disposed of as
hazardous waste.
SOPs (see Appendix B) shall be developed to include:
 Management of HD spills.
 Assurances that clean-up of a spill according to its size and type is handled by
workers who are trained in handling hazardous materials.
 Recognition that the size and type of the spill might determine who is authorized
to conduct the clean-up and decontamination and how the clean-up is
managed.
 Description of the protective equipment required for various spill sizes, the
possible spreading of material, restricted access to HD spills, and signs to be
posted.
 Use of an appropriate full-facepiece, chemical cartridge-type respirator for spills
that exceed the capacity of the spill kit, such as when an IV bag breaks or a line
disconnects and leaks, or where there is known or suspected airborne exposure
to vapors or gases.
 Location of spill kits and other clean-up materials in the immediate area where
exposures may occur.
The entity shall determine by policy when emergency management (including the
entity’s safety and hazardous materials personnel) shall be contacted.
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933
16. DISPOSAL
934
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938
Disposal of all HD waste (including unused and unusable HDs) shall comply with all
applicable federal and state regulations. All personnel who perform routine custodial
waste removal and cleaning activities in storage and preparation areas for HDs shall be
trained in appropriate procedures to protect themselves and the environment and to
prevent contamination.
939
940
17. ENVIRONMENTAL QUALITY AND CONTROL
941
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943
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946
947
948
949
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953
To ensure containment of HDs, environmental wipe sampling to detect uncontained
HDs should be performed routinely (e.g., initially as a benchmark and at least every 6
months, or more often as needed, to verify containment). This sampling should include
surface wipe sampling of the working area of C-PEC; countertops where finished
preparations are placed; areas adjacent to BSCs and CACIs, including the floor directly
under the working area; and patient administration areas.
Common marker HDs that can be assayed include cyclophosphamide, ifosfamide,
methotrexate, fluorouracil, and platinum-containing drugs. If any measurable
contamination (cyclophosphamide levels more than 1.00 ng/cm2 have been found to
cause human uptake) is found by any of these quality assurance procedures,
practitioners shall identify, document, and contain the cause of contamination. Such
action may include reevaluating work practices, retraining, thorough
deactivation/decontamination/disinfection/cleaning, and improving engineering controls.
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955
Examples of improving engineering controls include implementing use of CSTDs or reassessing the types of C-PEC used.
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957
18. DOCUMENTATION
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966
967
The entity shall establish policies and procedures to ensure that compounding and
dispensing records meet the requirement of this chapter, chapters 795 and 797 ,
entity policy, and federal and state laws and regulations.
Activities that shall be documented include but are not limited to the acquisition,
preparation, and dispensing of a compounded HD, personnel training, and the use and
maintenance of equipment and supplies. These records shall be available for review by
the applicable authorities.
Policies and procedures shall be reviewed at least annually by the compounding
supervisor, and the review shall be documented. Revisions in forms or records shall be
made as needed and communicated to all compounding personnel.
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969
19. MEDICAL SURVEILLANCE
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997
The goal of medical surveillance is to minimize adverse health effects in workers
exposed to HDs. A medical surveillance program involves collecting and interpreting
data to detect changes in the health status of working populations potentially exposed to
hazardous substances. Medical surveillance augments and evaluates the protection
afforded by engineering controls, other administrative controls, good work practice,
PPE, and worker education about the hazards of the materials they work with or they
may come into contact with in the course of their duties.
Employers shall ensure that healthcare workers who are exposed to HDs are routinely
monitored as part of a medical surveillance program. Workers may be exposed to HDs
when they create aerosols, generate dust, clean up spills, or touch contaminated
surfaces when compounding, administering, or disposing of HDs or patient waste. This
includes workers who directly handle HDs, such as nurses, pharmacists, and pharmacy
technicians. In addition, other workers (e.g., patient care assistants, or environmental
services staff), who may come directly into contact with patient wastes within 48 hours
after a patient has received an HD, should be included in a medical surveillance
program.
Workers who are potentially exposed to chemical hazards should be monitored in a
systematic program of medical surveillance intended to prevent occupational injury and
disease. The purpose of surveillance is to identify the earliest reversible biologic effects
so that exposure can be reduced or eliminated before the employee sustains
irreversible damage. The information should help affected workers and identify and
correct system failures that may have resulted in harmful exposures.
The elements of a medical surveillance program are used to establish a baseline of
workers’ health and then monitor their future health for any changes that may result
from exposure to hazardous agents. Program results should be examined in aggregate
for trends that may be a sign of health changes related to exposure to HDs. Elements of
a medical surveillance program shall be consistent with the entity’s Human Resource
policies and shall include:
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1000
1001
1002
1003
 Development of an organized approach to identify workers who are potentially
exposed to HDs on the basis of their job duties
 Design of medical surveillance that is appropriate to the exposure
 Establishment of an initial baseline (pre-placement) of workers’ medical health
(including reproductive history) and occupational history (as an estimate of prior
exposure), such as:
- Records of drugs and quantities and dosage forms handled,
1004
1005
- Hours spent handling these drugs per week, and
1006
- Number of preparations/administrations per week.
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1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
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1025
 Exposure assessment of all employees who have worked with HDs is important,




and the maintenance of records is required by OSHA regulation concerning
access to employee exposure and medical records (29 CFR 1910.1020).
Monitor workers’ future health as it relates to potential exposures to hazardous
agents through periodic and routine physical examinations and reproductive
and general health questionnaires; exposure histories should also be updated.
Track current exposure, which includes careful documentation of an individual’s
routine exposure and any acute accidental exposures.
Monitoring of the data to identify prevention failure leading to disease
Development of a follow-up plan for workers who have shown health changes
suggesting toxicity or who have experienced an acute exposure. This follow-up
shall include evaluation of current engineering and administrative controls and
equipment to ensure that all systems are appropriately and accurately
implemented.
Completion of an exit examination to document the information on the
employee’s medical, reproductive, and exposure histories. Examination and
laboratory evaluation should be guided by the individual’s history of exposures,
and follow the outline of the periodic evaluation.
19.1 Follow-up Plan
1026
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1030
The occurrence of exposure-related disease or health changes should prompt
immediate re-evaluation of primary preventive measures (e.g., administrative and
engineering controls, PPE, and others). In this manner, medical surveillance acts as a
check on the appropriateness of controls already in use.
The employer should take the following actions:
1031
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1034
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1036
 Post-exposure examinations: Post-exposure evaluation is tailored to the type of
exposure (e.g., spills or needle sticks from syringes containing HDs). An
assessment of the extent of exposure is made and included in the confidential
database (discussed below) and in an incident report. The physical examination
focuses on the involved area as well as other organ systems commonly
affected (i.e., the skin and mucous membranes; the pulmonary system for
1037
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1039
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1043
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







aerosolized HDs). Treatment and laboratory studies follow as indicated and
should be guided by emergency protocols.
Compare performance of controls with recommended standards: Conduct
environmental sampling when analytical methods are available.
Verify and document that all controls are in proper operating condition.
Verify and document that the worker complied with existing policies or when new
policies went into effect. Review policies for the use of PPE and employee
compliance with PPE use and policies. Review availability of appropriate PPE
including ASTM-tested chemotherapy gloves, low-permeation gowns,
respiratory protection, and eye protection.
Develop and document a plan of action that will prevent additional worker
exposure.
Ensure a confidential two-way communication between the worker and the
employee health units regarding notification, discussions about a change in
health condition, or finding of an adverse health effect.
Provide and document a follow-up medical survey that the plan implemented is
effective.
Ensure confidential notification of any adverse health effect to an exposed worker
and offer alternative duty or temporary reassignment.
Provide ongoing medical surveillance of all workers at risk to determine whether
the plan implemented is effective.
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1063
Refer to the guidelines of professional organizations such as the American Society of
Health-System Pharmacists (ASHP), NIOSH, and ONS, which recommend medical
surveillance as the recognized standard of occupational health practice for personnel
who handle HD. The American College of Occupational and Environmental Medicine
(ACOEM) also recommends surveillance for these workers in their Reproductive Hazard
Management Guidelines.
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APPENDIX A: ACRONYMS AND DEFINITIONS
1066
ACRONYMS
1067
ACOEM American College of Occupational and Environmental Medicine
ACPH
Air changes per hour
ALARA As low as reasonably achievable
API
Active pharmaceutical ingredient
ASHP
American Society of Health-System Pharmacists
ASTM
American Society for Testing and Materials
BSC
Biological safety cabinet
BUD
Beyond-use date
CACI
Compounding aseptic containment isolator
CAI
Compounding aseptic isolator
CDC
Centers for Disease Control and Prevention
CETA
Controlled Environment Testing Association
CFR
Code of Federal Regulations
C-PEC Containment primary engineering control
C-SCA Containment segregated componding area
C-SEC Containment secondary engineering control
CSP
Compounded sterile preparation
CSTD
Closed system drug-transfer device
CVE
Containment ventilated enclosure
EPA
Environmental Protection Agency
GHS
Globally harmonized system of classification and labeling of chemicals
HCS
Hazardous Communication Standard
HD
Hazardous drug
HEPA
High efficiency particulate air
IV
Intravenous
LAFW
Laminar air flow workbench
NIOSH National Institute for Occupational Safety and Health
ONS
Oncology Nursing Society
OSHA
Occupational Safety and Health Administration
PEC
Primary engineering control
PPE
Personal protective equipment
RCRA
Resource Conservation and Recovery Act
SDS
Safety Data Sheet
SOP
Standard Operating Procedure
ULPA
Ultra low particulate air
USP
United States Pharmacopeia
DEFINITIONS
1068
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Active pharmaceutical ingredient (API): Any substance or mixture of substances
intended to be used in the compounding of a drug preparation, thereby becoming the
active ingredient in that preparation and furnishing pharmacological activity or other
direct effect in the diagnosis, cure, mitigation treatment, or prevention of disease in
humans and animals or affecting the structure and function of the body.
1074
1075
Alternative duty:
of HDs.
Performance of other tasks that do not include the direct handling
1076
1077
1078
1079
1080
1081
Anteroom: Transition area between the general area and the room containing the CPEC. Hand hygiene, garbing, staging of components, order entry, and other particlegenerating activities are performed in the anteroom. For sterile compounding, the
anteroom shall meet ISO Class 7 (for all references to ISO classification, see Table 1)
and also provides assurance that pressure relationships between rooms are constantly
maintained.
1082
1083
1084
Batch: More than one unit of a compounded preparation that is intended to have
uniform character and quality within specified limits, prepared in a single process, and
completed during the same and limited time period.
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1086
Beyond-use date (BUD): The date or time after which a compounded preparation
shall not be used, stored, or transported (see 795 and 797 for additional details).
1087
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1089
Biohazard: Infectious agent or hazardous biological material that presents a risk or
potential risk to the health of humans, animals, or the environment. The risk can be
direct through infection or indirect through damage to the environment.
1090
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1093
Biological safety cabinet (BSC): A ventilated cabinet often used for preparation of
hazardous drugs. BSCs shall be NSF/ANSI listed. These cabinets are divided into three
general classes (Class I, Class II, and Class III). Class II BSCs are further divided into
types (Type A1, Type A2, Type B1, and Type B2). See Appendix C for details.
1094
1095
1096
Buffer room: Part of the HD compounding area under negative pressure where the
C-PEC is physically located. Activities that occur in this area are limited to the
preparation and staging of components and supplies used when compounding HDs.
1097
1098
1099
Chemotherapy glove: A medical glove that meets the ASTM Standard Practice
(D6978-05-2013) for Assessment of Resistance of Medical Gloves to Permeation by
Chemotherapy Drugs.
1100
1101
1102
Cleaning: The removal of soil (e.g., organic and inorganic material) from objects and
surfaces, normally accomplished manually or mechanically using water with detergents
or enzymatic products.
1103
1104
1105
1106
1107
1108
Cleanroom: A room in which the concentration of airborne particles is controlled
through directional airflow and HEPA-filtered air supply to meet a specified airborne
particulate cleanliness class. Microorganisms in the environment are monitored so that
a microbial level for air, surface, and personnel are not exceeded for a specified ISOclassified space (see 1116 Microbiological Control and Monitoring of Aseptic
Processing Environments and also the definition of Buffer room).
1109
1110
1111
Closed system drug-transfer device (CSTD): A drug transfer device that
mechanically prohibits the transfer of environmental contaminants into the system and
the escape of HD or vapor concentrations outside of the system.
1112
1113
1114
Compounded preparation: A nonsterile or sterile drug or nutrient preparation that is
compounded in a licensed pharmacy or other healthcare-related facility pursuant to the
order or anticipation of order of a licensed prescriber.
1115
1116
1117
1118
1119
1120
1121
1122
1123
1124
Compounding aseptic containment isolator (CACI): A specific type of CAI that is
designed for compounding of sterile HDs. The CACI shall be certified in accordance
with CETA-CAG-002, designed to provide worker protection from exposure to
undesirable levels of airborne drugs throughout the compounding and material transfer
processes and to provide an aseptic environment with unidirectional airflow for
compounding sterile preparations. Air exchanged with the surrounding environment
shall not occur unless it is first passed through a microbially retentive filter (HEPA
minimum) system capable of containing airborne concentrations of the physical size and
state of the drug being compounded. Exhaust air from the isolator shall be appropriately
removed by properly designed building ventilation.
1125
1126
1127
1128
1129
1130
1131
Compounding aseptic isolator (CAI): An isolator specifically designed for
compounding sterile, non-hazardous pharmaceutical ingredients or preparations that
shall be certified in accordance with CETA-CAG-002. It is designed to maintain an
aseptic compounding environment within the isolator throughout the compounding and
material transfer processes. Air exchange into the isolator from the surrounding
environment shall not occur unless the air has first passed through a microbially
retentive filter (HEPA minimum). A CAI shall not be used for the manipulation of HDs.
1132
1133
1134
1135
Compounding personnel: Individuals who participate in the compounding process
who are competent and knowledgeable and are responsible for the preparation of HDs,
using information from this chapter, the entity’s SOPs, and instructions from the
compounding supervisor.
1136
1137
1138
1139
Compounding supervisor: The individual who is responsible for developing and
implementing appropriate procedures; overseeing facility compliance with this chapter
and other applicable laws, regulations, and standards; ensuring competency of
personnel; and assuring environmental control of the compounding areas.
1140
1141
1142
Containment primary engineering control (C-PEC): A ventilated device designed
and operated to minimize worker and environmental exposures to HDs by controlling
emissions of airborne contaminants through the following:
1143
1144
1145
1146
1147
1148
 The full or partial enclosure of a potential contaminant source
 The use of airflow capture velocities to capture and remove airborne
contaminants near their point of generation
 The use of air pressure relationships that define the direction of airflow into the
cabinet
 The use of HEPA filtration on all potentially contaminated exhaust streams
1149
1150
1151
1152
Examples of C-PECs include Class I, II, or III BSCs, CACIs, and CVE (e.g., powder
hood).
C-PECs used for nonsterile compounding do not need to have ISO Class 5 air quality.
C-PECs used for sterile compounding shall have ISO Class 5 air quality (see Table 2).
1153
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1155
Containment secondary engineering control (C-SEC): The C-SEC is the room in
which the C-PEC is placed. It incorporates specific design and operational parameters
required to contain the potential hazard within the compounding room, e.g., restricted
1156
1157
access, barriers, special construction technique, ventilation, and room pressurization
are components of the secondary control strategy.
1158
1159
1160
1161
1162
Containment segregated compounding area (C-SCA): A type of C-SEC with
nominal airflow and room pressurization requirements as they pertain to HD
compounding. The C-SCA is limited for use with a BSC when preparing low- or
medium-risk level CSPs with 12-hour or less BUDs, preparing CSPs in a CACI that
meets the requirements in 797 , or preparing nonsterile HDs in a C-PEC.
1163
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1165
Containment ventilated enclosure (CVE): A full or partial enclosure that uses
ventilation principles to capture, contain, and remove airborne contaminants (through
HEPA filtration) and prevent their release into the work environment (see Table 2).
1166
Critical area:
1167
1168
1169
1170
Critical site: A location that includes any component or fluid pathway surfaces (e.g.,
vial septa, injection ports, beakers) or openings (e.g., opened ampules, needle hubs)
exposed and at risk of direct contact with the air (e.g., ambient room or HEPA filtered),
moisture (e.g., oral and mucosal secretions) or touch contamination.
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1172
Deactivation: Treatment of an HD with another chemical, heat, ultraviolet light, or
other agent to create a less hazardous agent.
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1174
Decontamination:
chemical means.
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1176
Disinfectant: A chemical agent that destroys or inhibits the growth of microorganisms
that cause disease.
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1178
1179
1180
1181
Engineering control: Primary, secondary, and supplemental devices designed to
eliminate or reduce worker exposure to a chemical, biological, radiological, ergonomic,
or physical hazard, and in the case of CSPs, to protect the compounded product from
environmental contamination. Examples include ventilation controls such as BSCs or
CACIs, CSTDs, retracting syringe needles, and safety interlocks.
1182
1183
1184
Entity: Pharmacy, hospital, physician’s office, clinic, veterinary office, or other
locations wherever HDs are received, stored, prepared, dispensed, and distributed to a
final user or healthcare personnel who will administer the HD.
1185
1186
1187
1188
Expiration/expiry date: The expiration date identifies the time during which the
article may be expected to meet the requirements of the compendia monograph,
provided it is kept under the prescribed storage conditions (see General Notices and
Requirements10.40.100).
1189
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1191
Globally harmonized system of classification and labeling of chemicals
(GHS): A system for standardizing and harmonizing the classification and labeling of
chemicals.
1192
1193
1194
Goggles: Tight-fitting eye protection that completely covers the eyes, eye sockets,
and the facial area that immediately surrounds the eyes and that provide protection from
impact, dust, and splashes. Some goggles will fit over corrective lenses.
An ISO Class 5 (see Table 1) environment.
Inactivation, neutralization, or removal of HDs, usually by
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1197
1198
Hazardous communication standard (HCS): A U.S. government regulation
designed to ensure that the hazards of all chemicals produced or imported are
evaluated and that details regarding their hazards are transmitted to employers and
employees.
1199
Hazardous drug (HD):
1200
1201
1202
1203
1204
1205






Any drug identified by at least one of the following six criteria:
Carcinogenicity
Teratogenicity or developmental toxicity
Reproductive toxicity in humans
Organ toxicity at low doses in humans or animals
Genotoxicity
New drugs that mimic existing hazardous drugs in structure or toxicity
1206
1207
1208
1209
High efficiency particulate air (HEPA) filtration: An extended-medium, dry-type
filter in a rigid frame, having a minimum particle collection efficiency of 99.97% for 0.3µm mass-median diameter particles when tested at a rated airflow in accordance with
MIL STD 282 using IEST Recommended Standard RP-CC001.5.
1210
1211
1212
1213
1214
Labeling: A term that designates all labels and other written, printed, or graphic
matter on an immediate container of an article or preparation, or on, or in, any package
or wrapper in which it is enclosed, except any outer shipping container. The term “label”
designates that part of the labeling on the immediate container [see General Notices
and Requirements and 21 USC 321 (k) and (m)].
1215
1216
1217
Laminar air flow workbench (LAFW): A primary engineering control designed for
use when compounding sterile non-HDs. An LAFW shall not be used for the
manipulation of HDs.
1218
1219
Negative-pressure room: A room that is at a lower pressure than the adjacent
spaces and, therefore, the net flow of air is into the room.
1220
1221
1222
1223
Pass-through: An enclosure with interlocking doors positioned between two spaces
for the purpose of reducing particulate transfer while moving materials from one space
to another. A pass-through serving negative-pressure rooms shall be equipped with
sealed doors.
1224
1225
1226
Personal protective equipment (PPE): Items such as gloves, gowns, respirators,
goggles, face shields, and others that protect individual workers from hazardous
physical or chemical exposures.
1227
1228
1229
1230
Pharmaceutical product: A commercially manufactured drug, biologic, or nutrient
that has been evaluated for safety and efficacy by the FDA. Products are accompanied
by full prescribing information, which is commonly known as the FDA-approved
manufacturer’s labeling or product package insert.
1231
1232
Positive-pressure room: A room that is at a higher pressure than the adjacent
spaces and, therefore, the net flow of air is out of the room.
1233
1234
Primary engineering control (PEC): A ventilated device that provides a prescribed
environment for the exposure of critical sites and when desired, protects workers and
1235
1236
1237
the environment from exposure to the compounds under manipulation. PECs used for
manipulation of HDs shall be designed for containment (see also Containment primary
engineering control).
1238
1239
1240
1241
Resource conservation and recovery act (RCRA) empty: A vial, ampule, IV bag,
or other container that once held a drug regulated under the Resource Conservation
and Recovery Act, if all the contents have been removed that can be removed by
normal means and no more than 3% of the contents by weight remain.
1242
1243
1244
Safety data sheet (SDS): An informational document that provides written or printed
material concerning a hazardous chemical that is prepared in accordance with the HCS
[previously known as a Material Safety Data Sheet (MSDS)].
1245
1246
Spill kit: A container of supplies, warning signage, and related materials used to
contain the spill of an HD.
1247
1248
1249
1250
Sterilization: A process that destroys or eliminates all forms of microbial life
(including spores) and is carried out by physical or chemical methods. Steam under
pressure, dry heat, ethylene oxide gas, hydrogen peroxide gas plasma, and liquid
chemicals are the principal sterilizing agents used in healthcare settings.
1251
1252
1253
1254
1255
1256
Supplemental engineering control: An adjunct control (e.g., CSTD) used in
concurrence with primary and secondary control strategies. Supplemental engineering
controls offer additional levels of protection and may facilitate enhanced occupational
protection because the HD is handled outside of the protective controls of primary and
secondary control environments (e.g., post-compounding transit, administration, and
disposal).
1257
1258
1259
Trace chemotherapy waste: Components such as vials, ampules, IV bags, etc.,
which once held antineoplastic agents but after use are considered to be “RCRA
empty”.
1260
1261
1262
Trace contaminated waste: Items used in the handling, compounding, dispensing,
administration, or disposal of antineoplastic agents which are not overtly contaminated
(e.g., gowns, gloves, goggles, wipes).
1263
1264
APPENDIX B: SUGGESTED STANDARD OPERATING PROCEDURES
1265
1266
1267
1268
1269
1270
1271
1272
 Policies and procedures for the safe handling of HDs shall be in place for all
situations in which these drugs are used throughout a facility. Chapters 795
and 797 list SOPs recommended for use for nonsterile and sterile
compounding. Additionally, the following HD-related procedures should be
considered:
- Comprehensive hazardous drug safety program
- Hazard communication program
1273
1274
- Entity policy for labeling containers from acquisition to disposal with
hazardous warnings
1275
- Procurement of HDs
1276
- Use of C-PECs, including work practices specific to the type of device used
1277
1278
- Use of PPE, including receipt and transport, compounding, administration,
disposal, and handling waste
1279
- Cleaning of C-PEC and surrounding areas
1280
- Cleaning solutions and dilutions
1281
- Spill control, including use and contents of spill kit, cleaning, and notification
1282
- Waste management of trace chemotherapy and hazardous waste
1283
- Medical surveillance
1284
1285
1286
1287
1288
1289
1290
1291
1292
1293
1294
1295
1296
1297
1298
1299
1300
1301
1302
1303
1304
1305
1306
1307
1308
1309
APPENDIX C: TYPES OF BIOLOGICAL SAFETY CABINETS
Class I: A BSC that protects personnel and the environment but does not protect the
product/preparation. Personnel protection is provided as a minimum velocity of 75
linear feet/min of unfiltered room air is drawn through the front opening and across the
work surface. The air is then passed through a HEPA/ULPA filter either into the room
or to the outside in the exhaust plenum, providing environmental protection.
Class II: Class II (Types A1, A2, B1, and B2) BSCs are partial barrier systems that
rely on the movement of air to provide personnel, environmental, and
product/preparation protection. Personnel and product/preparation protection is
provided by the combination of inward and downward airflow captured by the front
grille of the cabinet. Side-to-side cross-contamination of products/preparations is
minimized by the internal downward flow of HEPA/ULPA filtered air moving toward the
work surface and then drawn into the front and rear intake grilles. Environmental
protection is provided when the cabinet exhaust air is passed through a HEPA/ULPA
filter.
Type A1 (formerly, Type A): These Class II BSCs maintain a minimum inflow
velocity of 75 ft/min, have HEPA-filtered, down-flow air that is a portion of the mixed
down-flow and inflow air from a common plenum, may exhaust HEPA-filtered air
back into the laboratory or to the environment through an exhaust canopy, and may
have positive-pressure contaminated ducts and plenums that are not surrounded by
negative-pressure plenums. They are not suitable for use with volatile toxic
chemicals and volatile radionucleotides.
Type A2 (formerly, Type B3): These Class II BSCs maintain a minimum inflow
velocity of 100 ft/min, have HEPA-filtered, down-flow air that is a portion of the mixed
down-flow and inflow air from a common exhaust plenum, may exhaust HEPAfiltered air back into the laboratory or to the environment through an exhaust canopy,
and have all contaminated ducts and plenums under negative pressure or
surrounded by negative-pressure ducts and plenums. If these cabinets are used for
minute quantities of volatile toxic chemicals and trace amounts of radionucleotides,
they must be exhausted through properly functioning exhaust canopies.
Type B1: These Class II BSCs maintain a minimum inflow velocity of 100 ft/min,
have HEPA-filtered down-flow air composed largely of uncontaminated, recirculated
inflow air, exhaust most of the contaminated down-flow air through a dedicated duct
exhausted to the atmosphere after passing it through a HEPA filter, and have all
contaminated ducts and plenums under negative pressure or surrounded by
negative-pressure ducts and plenums. If these cabinets are used for work involving
minute quantities of volatile toxic chemicals and trace amounts of radionucleotides,
the work must be done in the directly exhausted portion of the cabinet.
Type B2 (total exhaust): These Class II BSCs maintain a minimum inflow velocity of
100 ft/min, have HEPA-filtered down-flow air drawn from the laboratory or the
outside, exhaust all inflow and down-flow air to the atmosphere after filtration through
a HEPA filter without recirculation inside the cabinet or return to the laboratory, and
have all contaminated ducts and plenums under negative pressure or surrounded by
directly exhausted negative-pressure ducts and plenums. These cabinets may be
used with volatile toxic chemicals and radionucleotides.
1310
1311
1312
1313
1314
1315
1316
1317
1318
1319
1320
1321
1322
1323
1324
1325
1326
1327
1328
1329
1330
1331
1332
1333
1334
1335
1336
1337
1338
1339
Class III: The Class III BSC is designed for work with highly infectious microbiological
agents and other hazardous operations. It provides maximum protection for the
environment and the worker. It is a gas-tight enclosure with a viewing window that is
secured with locks and/or requires the use of tools to open. Both supply and exhaust
air are HEPA/ULPA filtered. Exhaust air must pass through two HEPA/ULPA filters in
series before discharge to the outdoors.
1340
1341
APPENDIX D: BEST PRACTICES FOR HANDLING HDS
1342
Activity
Location
Unpacking
HDs
Designated
receiving
area
Unpacking
damaged
shipping
containers
C-PEC
Class I device
designated for
this purpose or
Class I device
Pressure
(inches of
Minimum
water
HEPA filtration ACPH
column)
Activity
Location
C-PEC
Pressure
(inches of
Minimum
water
HEPA filtration ACPH
column)
used only for
nonsterile HD
preparations
Nonsterile
preparations
Sterile
preparations
1343
1344
1345
1346
Separate
room for
nonsterile
HDs
Negativepressure,
ventilated
enclosure, such
as a Class 1 BSC
or CVE
Not required if
hazardous
preparations
are handled
only in the CPEC
Negativepressure
ISO Class 7 Class II BSC or
room
CACI
Required in
supply to
maintain room
state of control
Negativepressure
SCA
Not required if
CACI meets
minimum
criteria
established in
the chapter
Class II BSC or
CACI
12
Minimum
0.01"
negative
30
Minimum
0.01"
negative
12
Minimum
0.01"
negative
APPENDIX E: EXAMPLES FOR DESIGN OF HAZARDOUS DRUG COMPOUNDING
AREAS
1348
1349
APPENDIX F: REQUIREMENTS FOR PERSONAL PROTECTIVE EQUIPMENT
1350
Activity
Description
Gloves
ASTM-tested
chemotherapy
gloves shall be
worn for all
handling of
HDs. Two
pairs are
required for
compounding,
administering,
managing a
spill, and
disposal of
HDs.
+a
If an industrial
glove is used
for receiving,
at least one
ASTM-tested
chemotherapy
glove shall be
Receiving
worn over the
suspected/broken industrial
supplies
glove.
Gown
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
Disposable,
long-sleeved
and cuffed
gowns, with a
solid front and
closure in the
back, made of
polyethylenecoated polypropylene or
other laminate
material
Not required
for routine use
when a CPEC is used.
Use eye and
face
protection
when
manipulating
HDs outside
of a C-PEC
and working at
or above eye
level, cleaning
a C-PEC, or
cleaning a
spill.
A NIOSHcertified N95
respirator is
generally
sufficient to
protect
against
particles.
Consult the
SDS for
respiratory
protection
information.
+
+
Receiving intact
supplies (remote
from
compounding
area)
Transporting
intact supplies or
compounded HDs
+
Receiving in
compounding
area
+
Stocking
+
+
+
Activity
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
Gloves
Gown
+
+
+
+
Outer glove
shall be sterile
(including
outer glove in
CACI).
+
+
compounding
area
Nonsterile
compounding
Sterile
compounding
Required
when
splashing or
aerosolization
is possible
+
+
Clean-up, routine
(such as following
compounding or
administration)
+
+
+
Collection and
disposal of
patient waste
+
+
+
Administering
+
Spills
+
+
+
+
Use an
appropriate,
fullfacepiece,
chemical
cartridgetype
respirator for
spills and
when there is
known or
suspected
airborne
exposure to
vapors or
gases.
Activity
a Gloves
Gown
Hair,
Face,
Beard,
Shoe Eye and Face Respiratory
Covers Protection
Protection
+ = Required.
1351
1352
APPENDIX G. BIBLIOGRAPHY
1353
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1371
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1377
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1379
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1381
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1383
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1386
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









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▪1S (USP38)