| (iv) routinely inspected, calibrated (if necessary),
or checked to ensure proper performance.
(C) Weighing, measuring, or otherwise manipulating
components that could generate airborne chemical particles (e.g.,
active pharmaceutical ingredients, added substances, and conventionally
manufactured products) shall be evaluated to determine if these activities
must be performed in a containment primary engineering control to
reduce the potential exposure to personnel or contamination of the
facility or compounded non-sterile preparations. The process evaluation
shall be carried out in accordance with the facility's SOPs, and the
assessment shall be documented.
(D) If a containment ventilated enclosure or biological
safety cabinet is used, it shall be certified at least every 12 months
or according to manufacturer specifications.
(5) Labeling. In addition to the labeling requirements
of the pharmacy's specific license classification, the label dispensed
or distributed pursuant to a prescription drug or medication order
shall contain the following.
(A) The generic name(s) or the official name(s) of
the principal active ingredient(s) of the compounded preparation.
(B) A statement that the preparation has been compounded
by the pharmacy. (An auxiliary label may be used on the container
to meet this requirement).
(C) A beyond-use date after which the compounded preparation
should not be used. The beyond-use date shall be determined as outlined
in Chapter 795 of the USP/NF concerning Pharmacy Compounding Non-Sterile
Preparations including the following:
(i) The pharmacist shall consider:
(I) physical and chemical properties of active ingredients;
(II) use of preservatives and/or stabilizing agents;
(III) dosage form;
(IV) storage containers and conditions; and
(V) scientific, laboratory, or reference data from
a peer reviewed source and retained in the pharmacy. The reference
data should follow the same preparation instructions for combining
components and packaged in a container with similar properties.
(ii) In the absence of stability information applicable
for a specific drug or preparation, the following maximum beyond-use
dates are to be used when the compounded preparation is packaged in
tight, light-resistant containers.
(I) Aqueous dosage forms. An aqueous preparation is
one that has a water activity equal to or greater than 0.6 (e.g.,
emulsions, gels, creams, solutions, sprays, or suspensions).
(-a-) Nonpreserved aqueous dosage forms: Not later
than 14 days when stored in a refrigerator.
(-b-) Preserved aqueous dosage forms: Not later than
35 days when stored at controlled room temperature or in a refrigerator.
(II) Nonaqueous dosage forms. A nonaqueous dosage form
is one that has a water activity less than 0.6.
(-a-) Nonaqueous oral liquids: Not later than 90 days
when stored at controlled room temperature or in a refrigerator.
(-b-) Other nonaqueous dosage forms: Not later than
180 days when stored at controlled room temperature or refrigerator.
Other nonaqueous dosage forms that have a water activity of less than
0.6 (e.g., capsules, tablets, granules, powders, nonaqueous topicals,
suppositories, and troches or lozenges).
(iii) Compounded non-sterile preparations requiring
shorter beyond-use dates. The beyond-use dates in subclauses (I) and
(II) of clause (ii) are the beyond-use dates for compounded nonsterile
preparations in the absence of specific stability information. However,
the designated person(s) shall still perform due diligence to determine
if there is existing stability data that would require a shorter beyond-use
date.
(I) The beyond-use date of the compounded non-sterile
preparation shall not exceed the shortest remaining expiration date
of any of the commercially available starting components.
(II) For compounded non-sterile preparations prepared
from one or more compounded components, the beyond-use date generally
shall not exceed the shortest beyond-use date of any of the individual
compounded components. However, there may be acceptable instances
when the beyond-use date of the final compounded non-sterile preparation
exceeds the beyond-use date assigned to compounded components (e.g.,
pH-altering solutions). If the assigned beyond-use date of the final
compounded non-sterile preparation exceeds the beyond-use date of
the compounded components, the physical, chemical, and microbiological
quality of the final compounded non-sterile preparation shall not
be negatively impacted.
(iv) Extending beyond-use dates for compounded non-sterile
preparations. Beyond-use date limits may be exceeded when supported
by valid scientific stability information for the specific compounded
preparation.
(I) Compounded non-sterile preparations with a USP/NF
monograph. When compounding from a USP/NF compounded preparation monograph
for the compounded non-sterile preparation, the beyond-use date shall
not exceed the beyond-use date specified in the monograph.
(II) Compounded non-sterile preparations with stability
information. If there is a stability study using a stability-indicating
analytical method for the active pharmaceutical ingredient(s), compounded
non-sterile preparation formulation, and material of composition of
the container closure that will be used, then the beyond-use date
indicated by the study may be used in lieu of the beyond-use date
specified in subclauses (I) and (II) of clause (ii) for aqueous and
nonaqueous dosage forms, up to a maximum of 180 days.
(III) If the beyond-use date of the compounded non-sterile
preparation is extended beyond the beyond-use date specified in subclauses
(I) and (II) of clause (ii), an aqueous compounded non-sterile preparation
must pass antimicrobial effectiveness testing.
(-a-) The designated person(s) may rely on antimicrobial
effectiveness testing that is conducted, or contracted for, once for
each formulation in the particular container closure system, including
materials of composition or the container closure system, in which
it will be packaged.
(-b-) Alternatively, the designated person(s) may rely
on antimicrobial effectiveness testing results provided by an FDA-registered
facility or published in peer-reviewed literature as long as the compounded
non-sterile preparation formulation, including any preservative, and
container closure materials of composition are the same as those tested,
unless a bracketing study is performed.
(-c-) When a bracketing study is performed, antimicrobial
effectiveness testing may be performed on a low concentration and
on a high concentration of the active ingredient in the formulation
to establish preservative effectiveness across various strengths of
the same formulation (e.g., bracketing). The concentration of all
other ingredients, including preservatives, must fall within the bracketed
range.
(6) Written drug information. Written information about
the compounded preparation or its major active ingredient(s) shall
be given to the patient at the time of dispensing. A statement which
indicates that the preparation was compounded by the pharmacy must
be included in this written information. If there is no written information
available, the patient should be advised that the drug has been compounded
and how to contact a pharmacist, and if appropriate the prescriber,
concerning the drug.
(7) Drugs, components, and materials used in non-sterile
compounding.
(A) Drugs used in non-sterile compounding shall be
USP/NF grade substances manufactured in an FDA-registered facility.
(B) If USP/NF grade substances are not available, or
when food, cosmetics, or other substances are or must be used, the
substance shall be of a chemical grade in one of the following categories:
(i) Chemically Pure (CP);
(ii) Analytical Reagent (AR); or
(iii) American Chemical Society (ACS); or
(iv) Food Chemical Codex; or
(C) If a drug, component, or material is not purchased
from an FDA-registered facility, the pharmacist shall establish purity
and stability by obtaining a Certificate of Analysis from the supplier
and the pharmacist shall compare the monograph of drugs in a similar
class to the Certificate of Analysis.
(D) A manufactured drug product may be a source of
active ingredient. Only manufactured drugs from containers labeled
with a batch control number and a future expiration date are acceptable
as a potential source of active ingredients. When compounding with
manufactured drug products, the pharmacist must consider all ingredients
present in the drug product relative to the intended use of the compounded
preparation.
(E) All components shall be stored in properly labeled
containers in a clean, dry area, under proper temperatures.
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