| preservative in the FDA-approved
product, or the physician requests an effective alternate dosage form)
or if the drug product is not commercially available. The unavailability
of such drug product must be documented prior to compounding. The
methodology for documenting unavailability includes maintaining a
copy of the wholesaler's notification showing back-ordered, discontinued,
or out-of-stock items. This documentation must be available in hard-copy
or electronic format for inspection by the board.
(E) A pharmacy may enter into an agreement to compound
and dispense prescription drug or medication orders for another pharmacy
provided the pharmacy complies with the provisions of §291.125
of this title (relating to Centralized Prescription Dispensing).
(F) Compounding pharmacies/pharmacists may advertise
and promote the fact that they provide sterile prescription compounding
services, which may include specific drug preparations and classes
of drugs.
(G) A pharmacy may not compound veterinary preparations
for use in food producing animals except in accordance with federal
guidelines.
(H) Compounded sterile preparations, including hazardous
drugs and radiopharmaceuticals, shall be prepared only under conditions
that protect the pharmacy personnel in the preparation and storage
areas.
(2) Microbial Contamination Risk Levels. Risk Levels
for sterile compounded preparations shall be as outlined in Chapter
797, Pharmacy Compounding--Sterile Preparations of the USP/NF and
as listed in this paragraph.
(A) Low-risk level compounded sterile preparations.
(i) Low-Risk conditions. Low-risk level compounded
sterile preparations are those compounded under all of the following
conditions:
(I) The compounded sterile preparations are compounded
with aseptic manipulations entirely within ISO Class 5 or better air
quality using only sterile ingredients, products, components, and
devices;
(II) The compounding involves only transfer, measuring,
and mixing manipulations using not more than three commercially manufactured
packages of sterile products and not more than two entries into any
one sterile container or package (e.g., bag, vial) of sterile product
or administration container/device to prepare the compounded sterile
preparation;
(III) Manipulations are limited to aseptically opening
ampules, penetrating disinfected 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;
(IV) For a low-risk level preparation, in the absence
of passing a sterility test the storage periods cannot exceed the
following time periods: before administration, the compounded sterile
preparation is stored properly and are exposed for not more than 48
hours at controlled room temperature, for not more than 14 days if
stored at a cold temperature, and for 45 days if stored in a frozen
state between minus 25 degrees Celsius and minus 10 degrees Celsius.
For delayed activation device systems, the storage period begins when
the device is activated.
(ii) Examples of Low-Risk Level Compounding. Examples
of low-risk level compounding include the following:
(I) Single volume transfers of sterile dosage forms
from ampules, bottles, bags, and vials using sterile syringes with
sterile needles, other administration devices, and other sterile containers.
The solution content of ampules shall be passed through a sterile
filter to remove any particles;
(II) Simple aseptic measuring and transferring with
not more than three packages of manufactured sterile products, including
an infusion or diluent solution to compound drug admixtures and nutritional
solutions.
(B) Low-Risk Level compounded sterile preparations
with 12-hour or less beyond-use date. Low-risk level compounded sterile
preparations are those compounded pursuant to a physician's order
for a specific patient under all of the following conditions:
(i) The compounded sterile preparations are compounded
in compounding aseptic isolator or compounding aseptic containment
isolator that does not meet the requirements described in paragraph
(7)(C) or (D) of this subsection (relating to Primary Engineering
Control Device) or the compounded sterile preparations are compounded
in laminar airflow workbench or a biological safety cabinet that cannot
be located within the buffer area;
(ii) The primary engineering control device shall be
certified and maintain ISO Class 5 for exposure of critical sites
and shall be located in a segregated compounding area restricted to
sterile compounding activities that minimizes the risk of contamination
of the compounded sterile preparation;
(iii) The segregated compounding area shall not be
in a location that has unsealed windows or doors that connect to the
outdoors or high traffic flow, or that is adjacent to construction
sites, warehouses, or food preparation.
(iv) For a low-risk level preparation compounded as
described in clauses (i) - (iii) of this subparagraph, administration
of such compounded sterile preparations must commence within 12 hours
of preparation or as recommended in the manufacturers' package insert,
whichever is less. However, the administration of sterile radiopharmaceuticals,
with documented testing of chemical stability, may be administered
beyond 12 hours of preparation.
(C) Medium-risk level compounded sterile preparations.
(i) Medium-Risk Conditions. Medium-risk level compounded
sterile preparations, are those compounded aseptically under low-risk
conditions and one or more of the following conditions exists:
(I) Multiple individual or small doses of sterile products
are combined or pooled to prepare a compounded sterile preparation
that will be administered either to multiple patients or to one patient
on multiple occasions;
(II) The compounding process includes complex aseptic
manipulations other than the single-volume transfer;
(III) The compounding process requires unusually long
duration, such as that required to complete the dissolution or homogenous
mixing (e.g., reconstitution of intravenous immunoglobulin or other
intravenous protein products);
(IV) The compounded sterile preparations do not contain
broad spectrum bacteriostatic substances and they are administered
over several days (e.g., an externally worn infusion device); or
(V) For a medium-risk level preparation, in the absence
of passing a sterility test the storage periods cannot exceed the
following time periods: before administration, the compounded sterile
preparations are properly stored and are exposed for not more than
30 hours at controlled room temperature, for not more than 9 days
at a cold temperature, and for 45 days in solid frozen state between
minus 25 degrees Celsius and minus 10 degrees Celsius.
(ii) Examples of medium-risk compounding. Examples
of medium-risk compounding include the following:
(I) Compounding of total parenteral nutrition fluids
using a manual or automated device during which there are multiple
injections, detachments, and attachments of nutrient source products
to the device or machine to deliver all nutritional components to
a final sterile container;
(II) Filling of reservoirs of injection and infusion
devices with more than three sterile drug products and evacuations
of air from those reservoirs before the filled device is dispensed;
(III) Filling of reservoirs of injection and infusion
devices with volumes of sterile drug solutions that will be administered
over several days at ambient temperatures between 25 and 40 degrees
Celsius (77 and 104 degrees Fahrenheit); and
(IV) Transfer of volumes from multiple ampules or vials
into a single, final sterile container or product.
(D) High-risk level compounded sterile preparations.
(i) High-risk Conditions. High-risk level compounded
sterile preparations are those compounded under any of the following
conditions:
(I) Non-sterile ingredients, including manufactured
products not intended for sterile routes of administration (e.g.,
oral) are incorporated or a non-sterile device is employed before
terminal sterilization.
(II) Any of the following are exposed to air quality
worse than ISO Class 5 for more than 1 hour:
(-a-) sterile contents of commercially manufactured
products;
(-b-) CSPs that lack effective antimicrobial preservatives;
and
(-c-) sterile surfaces of devices and containers for
the preparation, transfer, sterilization, and packaging of CSPs;
(III) Compounding personnel are improperly garbed and
gloved;
(IV) Non-sterile water-containing preparations are
exposed no more than 6 hours before being sterilized;
Cont'd... |
