|(a) Purpose. Pharmacies compounding sterile preparations,
prepackaging pharmaceutical products, and distributing those products
shall comply with all requirements for their specific license classification
and this section. The purpose of this section is to provide standards
(1) compounding of sterile preparations pursuant to
a prescription or medication order for a patient from a practitioner
in Class A-S, Class B, Class C-S, and Class E-S pharmacies;
(2) compounding, dispensing, and delivery of a reasonable
quantity of a compounded sterile preparation in Class A-S, Class B,
Class C-S, and Class E-S pharmacies to a practitioner's office for
office use by the practitioner;
(3) compounding and distribution of compounded sterile
preparations by a Class A-S pharmacy for a Class C-S pharmacy; and
(4) compounding of sterile preparations by a Class
C-S pharmacy and the distribution of the compounded preparations to
other Class C or Class C-S pharmacies under common ownership.
(b) Definitions. In addition to the definitions for
specific license classifications, the following words and terms, when
used in this section, shall have the following meanings, unless the
context clearly indicates otherwise.
(1) ACPE--Accreditation Council for Pharmacy Education.
(2) Airborne particulate cleanliness class--The level
of cleanliness specified by the maximum allowable number of particles
per cubic meter of air as specified in the International Organization
of Standardization (ISO) Classification Air Cleanliness (ISO 14644-1).
(A) ISO Class 5 (formerly Class 100) is an atmospheric
environment that contains less than 3,520 particles 0.5 microns in
diameter per cubic meter of air (formerly stated as 100 particles
0.5 microns in diameter per cubic foot of air);
(B) ISO Class 7 (formerly Class 10,000) is an atmospheric
environment that contains less than 352,000 particles 0.5 microns
in diameter per cubic meter of air (formerly stated as 10,000 particles
0.5 microns in diameter per cubic foot of air); and
(C) ISO Class 8 (formerly Class 100,000) is an atmospheric
environment that contains less than 3,520,000 particles 0.5 microns
in diameter per cubic meter of air (formerly stated as 100,000 particles
0.5 microns in diameter per cubic foot of air).
(3) Ancillary supplies--Supplies necessary for the
preparation and administration of compounded sterile preparations.
(4) Ante-area--An ISO Class 8 or better area where
personnel may perform hand hygiene and garbing procedures, staging
of components, order entry, labeling, and other high-particulate generating
activities. It is also a transition area that:
(A) provides assurance that pressure relationships
are constantly maintained so that air flows from clean to dirty areas;
(B) reduces the need for the heating, ventilating and
air conditioning (HVAC) control system to respond to large disturbances.
(5) Aseptic Processing--A mode of processing pharmaceutical
and medical preparations that involves the separate sterilization
of the preparation and of the package (containers-closures or packaging
material for medical devices) and the transfer of the preparation
into the container and its closure under at least ISO Class 5 conditions.
(6) Automated compounding device--An automated device
that compounds, measures, and/or packages a specified quantity of
individual components in a predetermined sequence for a designated
(7) Batch--A specific quantity of a drug or other material
that is intended to have uniform character and quality, within specified
limits, and is produced during a single preparation cycle.
(8) Batch preparation compounding--Compounding of multiple
sterile preparation units, in a single discrete process, by the same
individual(s), carried out during one limited time period. Batch preparation/compounding
does not include the preparation of multiple sterile preparation units
pursuant to patient specific medication orders.
(9) Beyond-use date--The date or time after which the
compounded sterile preparation shall not be stored or transported
or begin to be administered to a patient. The beyond-use date is determined
from the date or time the preparation is compounded.
(10) Biological Safety Cabinet, Class II--A ventilated
cabinet for personnel, product or preparation, and environmental protection
having an open front with inward airflow for personnel protection,
downward HEPA filtered laminar airflow for product protection, and
HEPA filtered exhausted air for environmental protection.
(11) Buffer Area--An ISO Class 7 area where the primary
engineering control area is physically located. Activities that occur
in this area include the preparation and staging of components and
supplies used when compounding sterile preparations.
(12) Clean room--A room in which the concentration
of airborne particles is controlled to meet a specified airborne particulate
cleanliness 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.
(13) Component--Any ingredient intended for use in
the compounding of a drug preparation, including those that may not
appear in such preparation.
(14) Compounding--The preparation, mixing, assembling,
packaging, or labeling of a drug or device:
(A) as the result of a practitioner's prescription
drug or medication order based on the practitioner-patient-pharmacist
relationship in the course of professional practice;
(B) for administration to a patient by a practitioner
as the result of a practitioner's initiative based on the practitioner-patient-pharmacist
relationship in the course of professional practice;
(C) in anticipation of prescription drug or medication
orders based on routine, regularly observed prescribing patterns;
(D) for or as an incident to research, teaching, or
chemical analysis and not for sale or dispensing, except as allowed
under §562.154 or Chapter 563 of the Occupations Code.
(15) Compounding Aseptic Isolator--A form of barrier
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 processes. Air exchange into the isolator from the surrounding
environment shall not occur unless it has first passed through a microbial
retentive filter (HEPA minimum).
(16) Compounding Aseptic Containment Isolator--A compounding
aseptic isolator designed to provide worker protection from exposure
to undesirable levels of airborne drug 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 (HEPA minimum) system capable of containing
airborne concentrations of the physical size and state of the drug
being compounded. Where volatile hazardous drugs are prepared, the
exhaust air from the isolator should be appropriately removed by properly
designed building ventilation.
(17) Critical Area--An ISO Class 5 environment.
(18) Critical Sites--A location that includes any component
or fluid pathway surfaces (e.g., vial septa, injection ports, beakers)
or openings (e.g., opened ampuls, needle hubs) exposed and at risk
of direct contact with air (e.g., ambient room or HEPA filtered),
moisture (e.g., oral and mucosal secretions), or touch contamination.
Risk of microbial particulate contamination of the critical site increases
with the size of the openings and exposure time.
(19) Device--An instrument, apparatus, implement, machine,
contrivance, implant, in-vitro reagent, or other similar or related
article, including any component part or accessory, that is required
under federal or state law to be ordered or prescribed by a practitioner.
(20) Direct Compounding Area--A critical area within
the ISO Class 5 primary engineering control where critical sites are
exposed to unidirectional HEPA-filtered air, also known as first air.
(21) Disinfectant--An agent that frees from infection,
usually a chemical agent but sometimes a physical one, and that destroys
disease-causing pathogens or other harmful microorganisms but may
not kill bacterial and fungal spores. It refers to substances applied
to inanimate objects.
(22) First Air--The air exiting the HEPA filter in
a unidirectional air stream that is essentially particle free.
(23) Hazardous Drugs--Drugs that, studies in animals
or humans indicate exposure to the drugs, have a potential for causing
cancer, development or reproductive toxicity, or harm to organs.
(24) Hot water--The temperature of water from the pharmacy's
sink maintained at a minimum of 105 degrees F (41 degrees C).
(25) HVAC--Heating, ventilation, and air conditioning.
(26) Immediate use--A sterile preparation that is not
prepared according to USP 797 standards (i.e., outside the pharmacy
and most likely not by pharmacy personnel) which shall be stored for
no longer than one hour after completion of the preparation.
(27) IPA--Isopropyl alcohol (2-propanol).
(28) Labeling--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.
(29) Media-Fill Test--A test used to qualify aseptic
technique of compounding personnel or processes and to ensure that
the processes used are able to produce sterile preparation without
microbial contamination. During this test, a microbiological growth
medium such as Soybean-Casein Digest Medium is substituted for the
actual drug preparation to simulate admixture compounding. The issues
to consider in the development of a media-fill test are the following:
media-fill procedures, media selection, fill volume, incubation, time
and temperature, inspection of filled units, documentation, interpretation
of results, and possible corrective actions required.
(30) Multiple-Dose Container--A multiple-unit container
for articles or preparations intended for potential administration
only and usually contains antimicrobial preservatives. The beyond-use
date for an opened or entered (e.g., needle-punctured) multiple-dose
container with antimicrobial preservatives is 28 days, unless otherwise
specified by the manufacturer.
(31) Negative Pressure Room--A room that is at a lower
pressure compared to adjacent spaces and, therefore, the net flow
of air is into the room.
(32) Office use--The administration of a compounded
drug to a patient by a practitioner in the practitioner's office or
by the practitioner in a health care facility or treatment setting,
including a hospital, ambulatory surgical center, or pharmacy in accordance
with Chapter 562 of the Act, or for administration or provision by
a veterinarian in accordance with §563.054 of the Act.
(33) Pharmacy Bulk Package--A container of a sterile
preparation for potential use that contains many single doses. The
contents are intended for use in a pharmacy admixture program and
are restricted to the preparation of admixtures for infusion or, through
a sterile transfer device, for the filling of empty sterile syringes.
The closure shall be penetrated only one time after constitution with
a suitable sterile transfer device or dispensing set, which allows
measured dispensing of the contents. The pharmacy bulk package is
to be used only in a suitable work area such as a laminar flow hood
(or an equivalent clean air compounding area).
(34) Prepackaging--The act of repackaging and relabeling
quantities of drug products from a manufacturer's original container
into unit dose packaging or a multiple dose container for distribution
within a facility licensed as a Class C pharmacy or to other pharmacies
under common ownership for distribution within those facilities. The
term as defined does not prohibit the prepackaging of drug products
for use within other pharmacy classes.
(35) Preparation or Compounded Sterile Preparation--A
sterile admixture compounded in a licensed pharmacy or other healthcare-related
facility pursuant to the order of a licensed prescriber. The components
of the preparation may or may not be sterile products.
(36) Primary Engineering Control--A device or room
that provides an ISO Class 5 environment for the exposure of critical
sites when compounding sterile preparations. Such devices include,
but may not be limited to, laminar airflow workbenches, biological
safety cabinets, compounding aseptic isolators, and compounding aseptic
(37) Product--A commercially manufactured sterile drug
or nutrient that has been evaluated for safety and efficacy by the
U.S. Food and Drug Administration (FDA). Products are accompanied
by full prescribing information, which is commonly known as the FDA-approved
manufacturer's labeling or product package insert.
(38) Positive Control--A quality assurance sample prepared
to test positive for microbial growth.