| (H) A pharmacy may not compound a preparation that
contains ingredients appearing on a federal Food and Drug Administration
list of drug products withdrawn or removed from the market for safety
reasons.
(13) Compounding process.
(A) Standard operating procedures (SOPs). All significant
procedures performed in the compounding area shall be covered by written
SOPs designed to ensure accountability, accuracy, quality, safety,
and uniformity in the compounding process. At a minimum, SOPs shall
be developed and implemented for:
(i) the facility;
(ii) equipment;
(iii) personnel;
(iv) preparation evaluation;
(v) quality assurance;
(vi) preparation recall;
(vii) packaging; and
(viii) storage of compounded sterile preparations.
(B) USP/NF. Any compounded formulation with an official
monograph in the USP/NF shall be compounded, labeled, and packaged
in conformity with the USP/NF monograph for the drug.
(C) Personnel Cleansing and Garbing.
(i) Any person with an apparent illness or open lesion,
including rashes, sunburn, weeping sores, conjunctivitis, and active
respiratory infection, that may adversely affect the safety or quality
of a drug preparation being compounded shall be excluded from working
in ISO Class 5, ISO Class 7, and ISO Class 8 compounding areas until
the condition is remedied.
(ii) Before entering the buffer area, compounding personnel
must remove the following:
(I) personal outer garments (e.g., bandanas, coats,
hats, jackets, scarves, sweaters, vests);
(II) all cosmetics, because they shed flakes and particles;
and
(III) all hand, wrist, and other body jewelry or piercings
(e.g., earrings, lip or eyebrow piercings) that can interfere with
the effectiveness of personal protective equipment (e.g., fit of gloves
and cuffs of sleeves).
(iii) The wearing of artificial nails or extenders
is prohibited while working in the sterile compounding environment.
Natural nails shall be kept neat and trimmed.
(iv) Personnel shall don personal protective equipment
and perform hand hygiene in an order that proceeds from the dirtiest
to the cleanest activities as follows:
(I) Activities considered the dirtiest include donning
of dedicated shoes or shoe covers, head and facial hair covers (e.g.,
beard covers in addition to face masks), and face mask/eye shield.
Eye shields are optional unless working with irritants like germicidal
disinfecting agents or when preparing hazardous drugs.
(II) After donning dedicated shoes or shoe covers,
head and facial hair covers, and face masks, personnel shall perform
a hand hygiene procedure by removing debris from underneath fingernails
using a nail cleaner under running warm water followed by vigorous
hand washing. Personnel shall begin washing arms at the hands and
continue washing to elbows for at least 30 seconds with either a plain
(non-antimicrobial) soap, or antimicrobial soap, and water while in
the ante-area. Hands and forearms to the elbows shall be completely
dried using lint-free disposable towels, an electronic hands-free
hand dryer, or a HEPA filtered hand dryer.
(III) After completion of hand washing, personnel shall
don clean non-shedding gowns with sleeves that fit snugly around the
wrists and enclosed at the neck.
(IV) Once inside the buffer area or segregated compounding
area, and prior to donning sterile powder-free gloves, antiseptic
hand cleansing shall be performed using a waterless alcohol-based
surgical hand scrub with persistent activity following manufacturers'
recommendations. Hands shall be allowed to dry thoroughly before donning
sterile gloves.
(V) Sterile gloves that form a continuous barrier with
the gown shall be the last item donned before compounding begins.
Sterile gloves shall be donned using proper technique to ensure the
sterility of the glove is not compromised while donning. The cuff
of the sterile glove shall cover the cuff of the gown at the wrist.
When preparing hazardous preparations, the compounder shall double
glove or shall use single gloves ensuring that the gloves are sterile
powder-free chemotherapy-rated gloves. Routine application of sterile
70% IPA shall occur throughout the compounding day and whenever non-sterile
surfaces are touched.
(v) When compounding personnel shall temporarily exit
the buffer area during a work shift, the exterior gown, if not visibly
soiled, may be removed and retained in the ante-area, to be re-donned
during that same work shift only. However, shoe covers, hair and facial
hair covers, face mask/eye shield, and gloves shall be replaced with
new ones before re-entering the buffer area along with performing
proper hand hygiene.
(vi) During high-risk level compounding activities
that precede terminal sterilization, such as weighing and mixing of
non-sterile ingredients, compounding personnel shall be garbed and
gloved the same as when performing compounding in an ISO Class 5 environment.
Properly garbed and gloved compounding personnel who are exposed to
air quality that is either known or suspected to be worse than ISO
Class 7 shall re-garb personal protective equipment along with washing
their hands properly, performing antiseptic hand cleansing with a
sterile 70% IPA-based or another suitable sterile alcohol-based surgical
hand scrub, and donning sterile gloves upon re-entering the ISO Class
7 buffer area.
(vii) When compounding aseptic isolators or compounding
aseptic containment isolators are the source of the ISO Class 5 environment,
at the start of each new compounding procedure, a new pair of sterile
gloves shall be donned within the CAI or CACI. In addition, the compounding
personnel should follow the requirements as specified in this subparagraph,
unless the isolator manufacturer can provide written documentation
based on validated environmental testing that any components of personal
protective equipment or cleansing are not required.
(14) Quality Assurance.
(A) Initial Formula Validation. Prior to routine compounding
of a sterile preparation, a pharmacy shall conduct an evaluation that
shows that the pharmacy is capable of compounding a preparation that
is sterile and that contains the stated amount of active ingredient(s).
(i) Low risk level preparations.
(I) Quality assurance practices include, but are not
limited to the following:
(-a-) Routine disinfection and air quality testing
of the direct compounding environment to minimize microbial surface
contamination and maintain ISO Class 5 air quality;
(-b-) Visual confirmation that compounding personnel
are properly donning and wearing appropriate items and types of protective
garments and goggles;
(-c-) Review of all orders and packages of ingredients
to ensure that the correct identity and amounts of ingredients were
compounded; and
(-d-) Visual inspection of compounded sterile preparations,
except for sterile radiopharmaceuticals, to ensure the absence of
particulate matter in solutions, the absence of leakage from vials
and bags, and the accuracy and thoroughness of labeling.
(II) Example of a Media-Fill Test Procedure. This,
or an equivalent test, is performed at least annually by each person
authorized to compound in a low-risk level under conditions that closely
simulate the most challenging or stressful conditions encountered
during compounding of low-risk level sterile preparations. Once begun,
this test is completed without interruption within an ISO Class 5
air quality environment. Three sets of four 5-milliliter aliquots
of sterile fluid culture media are transferred with the same sterile
10-milliliter syringe and vented needle combination into separate
sealed, empty, sterile 30-milliliter clear vials (i.e., four 5-milliliter
aliquots into each of three 30-milliliter vials). Sterile adhesive
seals are aseptically affixed to the rubber closures on the three
filled vials. The vials are incubated within a range of 20 - 35 degrees
Celsius for a minimum of 14 days. Failure is indicated by visible
turbidity in the medium on or before 14 days. The media-fill test
must include a positive-control sample.
(ii) Medium risk level preparations.
(I) Quality assurance procedures for medium-risk level
compounded sterile preparations include all those for low-risk level
compounded sterile preparations, as well as a more challenging media-fill
test passed annually, or more frequently.
(II) Example of a Media-Fill Test Procedure. This,
or an equivalent test, is performed at least annually under conditions
that closely simulate the most challenging or stressful conditions
encountered during compounding. This test is completed without interruption
within an ISO Class 5 air quality environment. Six 100-milliliter
aliquots of sterile Soybean-Casein Digest Medium are aseptically transferred
by gravity through separate tubing sets into separate evacuated sterile
containers. The six containers are then arranged as three pairs, Cont'd... |
