The following words and terms, when used in this subchapter,
shall have the following meanings:
"Ante area" means an ISO class 8 or better area where
personnel hand hygiene and garbing procedures, staging of components, order
entry, labeling, and other high-particulate-generating activities are
performed. The "ante area" is also a transition area that:
1. Provides assurance that pressure relationships are
constantly maintained so that air flows from clean to dirty areas; and
2. Reduces the need for the heating, ventilating, and
air-conditioning (HVAC) control system to respond to large disturbances.
"Biological safety cabinet" means a ventilated cabinet for
compounded sterile preparations that has an open front with inward airflow for
personnel protection, downward high-efficiency particulate air (HEPA)-filtered
laminar airflow for product protection, and HEPA-filtered exhaust air for
environmental protection.
"Buffer area" means an ISO class 7 area where the primary
engineering control is physically located and where the preparation and staging
of components and supplies used in compounding sterile preparations
occurs.
"Cleanroom" means a room in which the concentration of
airborne particles is controlled to meet a specified airborne particulate
cleanliness (ISO) class. Microorganisms in the environment are monitored, so
that a microbial level for air, surface, and personnel gear are not exceeded
for a specified cleanliness class. A "cleanroom" includes a buffer area or room
and an ante area or room.
"Compounding" means the preparation, mixing, assembling,
packaging, or labeling of a drug or device as the result of a practitioner's
prescription or medication order or initiative based on the relationship of the
practitioner or the patient with the pharmacist in the course of professional
practice, or for the purpose of, or incident to, research, teaching, or
chemical analysis and not for sale or dispensing. Compounding also includes the
preparation of drugs or devices in anticipation of prescriptions or medication
orders based on routine, regularly-observed prescribing patterns. Compounding
includes mixing, reconstituting, or assembling a drug according to the
product's labeling or to the manufacturer's directions.
"Compounding aseptic containment isolator" means a
compounding aseptic isolator designed to provide worker protection from
exposure to undesirable levels of airborne hazardous drugs throughout the
compounding and material transfer processes and to provide an aseptic
environment for compounding sterile preparations. Air exchange with the
surrounding environment should not occur unless the air is first passed through
a microbial retentive filter (high-efficiency particulate air (HEPA) minimum)
system capable of containing airborne concentrations of the physical size and
state of the drug being compounded.
"Compounding aseptic isolator" means a form of isolator
specifically designed for compounding pharmaceutical ingredients or
preparations. It is designed to maintain an aseptic compounding environment
within the isolator throughout the compounding and material transfer process.
Air exchanges into the isolator from the surrounding environment should not
occur unless the air has first passed through a microbially retentive filter
(high-efficiency particulate air (HEPA) minimum).
"Immediate use compounded sterile preparations" means
preparations intended for emergency patient care and involve only simple
aseptic measuring and transfer manipulations of no more than three sterile
non-hazardous commercial drug and diagnostic radiopharmaceutical drug products,
including an infusion or diluent solution. Unless required for the preparation,
the compounding process occurs continuously without delays or interruptions and
does not exceed one hour. Administration of immediate use compounded sterile
preparations shall begin within one hour of preparation or the compounded
sterile preparations shall be discarded. Immediate use compounded sterile
preparations shall not be compounded and stored for anticipated needs and shall
not be compounded as batch preparations. At no time during the compounding
process, nor prior to administration, are critical sites and ingredients of the
compounded sterile preparation directly exposed to contact contamination, such
as human touch, cosmetic flakes, or particulates, blood, human body substances,
and non-sterile inanimate sources.
"ISO class 5 air quality conditions" means conditions in
which the air particle count is no greater than a total of 3,520 particles of
0.5 micrometers and larger per cubic meter of air (100 particles per cubic
foot) that is supplied by high-efficiency particulate air (HEPA) or
HEPA-filtered air.
"ISO class 7 air quality conditions" means conditions in
which the air particle count is no greater than a total of 352,000 particles of
0.5 micrometers and larger per cubic meter of air (10,000 particles per cubic
foot) that is supplied by high-efficiency particulate air (HEPA) or
HEPA-filtered air.
"ISO class 8 air quality conditions" means conditions in
which the air particle count is no greater than a total of 3,520,000 particles
of 0.5 micrometers and larger per cubic meter of air (100,000 particles per
cubic foot) that is supplied by high-efficiency particulate air (HEPA) or
HEPA-filtered air.
"Negative pressure room" means a room that is at a lower
pressure than the adjacent spaces and, therefore, the net airflow is into the
room.
"Positive pressure room" means a room that is at a higher
pressure than the adjacent spaces and, therefore, the net airflow is out of the
room.
"Primary engineering control" means a device or room that
provides an ISO class 5 environment for the exposure of critical sites when
compounding sterile preparations. Such devices include laminar airflow
workbenches, biological safety cabinets, compounding aseptic isolators, and
compounding aseptic containment isolators.
"Risk levels for compounded sterile preparations" means the
established classification for compounded sterile preparations based on the
potential for microbial, chemical, and physical contamination of the
preparations and are defined as follows:
1. "Low-risk level compounded sterile preparations" means
preparations compounded with aseptic manipulations entirely within ISO class 5
or better air quality using only sterile ingredients, products, components, and
devices. The compounding process involves only assembling, transferring,
measuring, and mixing, using no more than three commercially manufactured
sterile products, and not more than two entries into one sterile container or
package to make the compounded sterile preparations. The compounding process is
limited to aseptically opening ampules, penetrating sterile stoppers on vials
with sterile needles and syringes, and transferring sterile liquids in sterile
syringes to sterile administration devices, package containers of other sterile
products, and containers for storage and dispensing.
2. "Medium-risk level compounded sterile preparations" means
preparations compounded under low-risk level conditions but which require
multiple individual or small doses of sterile products to be combined or pooled
to prepare compounded sterile preparations that will be administered either to
multiple patients or to one patient on multiple occasions. The compounding
process includes complex aseptic manipulations other than single volume
transfer, and requires an unusually long duration, such as that required to
complete dissolution or homogeneous mixing.
3. "High-risk level compounded sterile preparations" means
preparations compounded from non-sterile ingredients or from ingredients that
are incorporated using non-sterile equipment before terminal sterilization, or
from commercially manufactured sterile products that lack effective
antimicrobial preservatives and whose preparation, transfer, sterilization, and
packaging is performed in air quality worse than ISO class 5 for more than one
hour. Water-containing preparations that are stored for more than six hours
before terminal sterilization are also classified as high-risk level compounded
sterile preparations.
