| (vi) Prepared doses of hazardous drugs must be dispensed,
labeled with proper precautions inside and outside, and distributed
in a manner to minimize patient contact with hazardous agents.
(E) Blood-labeling procedures. When compounding activities
require the manipulation of a patient's blood-derived material (e.g.,
radiolabeling a patient's or donor's white blood cells), the manipulations
shall be performed in a ISO Class 5 biological safety cabinet located
in a buffer area and shall be clearly separated from routine material-handling
procedures and equipment used in preparation activities to avoid any
cross-contamination. The preparations shall not require sterilization.
(F) Cleaning and disinfecting the sterile compounding
areas. The following cleaning and disinfecting practices and frequencies
apply to direct and contiguous compounding areas, which include ISO
Class 5 compounding areas for exposure of critical sites as well as
buffer areas, ante-areas, and segregated compounding areas.
(i) The pharmacist-in-charge is responsible for developing
written standard operating procedures (SOPs) for cleaning and disinfecting
the direct and contiguous compounding areas and assuring the procedures
are followed.
(ii) These procedures shall be conducted at the beginning
of each work shift, before each batch preparation is started, when
there are spills, and when surface contamination is known or suspected
resulting from procedural breaches, and every 30 minutes during continuous
compounding of individual compounded sterile preparations, unless
a particular compounding procedure requires more than 30 minutes to
complete, in which case, the direct compounding area is to be cleaned
immediately after the compounding activity is completed.
(iii) Before compounding is performed, all items shall
be removed from the direct and contiguous compounding areas and all
surfaces are cleaned by removing loose material and residue from spills,
followed by an application of a residue-free disinfecting agent (e.g.,
IPA), which is allowed to dry before compounding begins. In a Class
B pharmacy, objects used in preparing sterile radiopharmaceuticals
(e.g., dose calibrator) which cannot be reasonably removed from the
compounding area shall be sterilized with an application of a residue-free
disinfection agent.
(iv) Work surfaces in the buffer areas and ante-areas,
as well as segregated compounding areas, shall be cleaned and disinfected
at least daily. Dust and debris shall be removed when necessary from
storage sites for compounding ingredients and supplies using a method
that does not degrade the ISO Class 7 or 8 air quality.
(v) Floors in the buffer area, ante-area, and segregated
compounding area shall be cleaned by mopping with a cleaning and disinfecting
agent at least once daily when no aseptic operations are in progress.
Mopping shall be performed by trained personnel using approved agents
and procedures described in the written SOPs. It is incumbent on compounding
personnel to ensure that such cleaning is performed properly.
(vi) In the buffer area, ante-area, and segregated
compounding area, walls, ceilings, and shelving shall be cleaned and
disinfected monthly. Cleaning and disinfecting agents shall be used
with careful consideration of compatibilities, effectiveness, and
inappropriate or toxic residues.
(vii) All cleaning materials, such as wipers, sponges,
and mops, shall be non-shedding, and dedicated to use in the buffer
area, ante-area, and segregated compounding areas and shall not be
removed from these areas except for disposal. Floor mops may be used
in both the buffer area and ante-area, but only in that order. If
cleaning materials are reused, procedures shall be developed that
ensure that the effectiveness of the cleaning device is maintained
and that repeated use does not add to the bio-burden of the area being
cleaned.
(viii) Supplies and equipment removed from shipping
cartons must be wiped with a disinfecting agent, such as sterile IPA.
After the disinfectant is sprayed or wiped on a surface to be disinfected,
the disinfectant shall be allowed to dry, during which time the item
shall not be used for compounding purposes. However, if sterile supplies
are received in sealed pouches, the pouches may be removed as the
supplies are introduced into the ISO Class 5 area without the need
to disinfect the individual sterile supply items. No shipping or other
external cartons may be taken into the buffer area or segregated compounding
area.
(ix) Storage shelving emptied of all supplies, walls,
and ceilings shall be cleaned and disinfected at planned intervals,
monthly, if not more frequently.
(x) Cleaning must be done by personnel trained in appropriate
cleaning techniques.
(xi) Proper documentation and frequency of cleaning
must be maintained and shall contain the following:
(I) date and time of cleaning;
(II) type of cleaning performed; and
(III) name of individual who performed the cleaning.
(G) Security requirements. The pharmacist-in-charge
may authorize personnel to gain access to that area of the pharmacy
containing dispensed sterile preparations, in the absence of the pharmacist,
for the purpose of retrieving dispensed prescriptions to deliver to
patients. If the pharmacy allows such after-hours access, the area
containing the dispensed sterile preparations shall be an enclosed
and lockable area separate from the area containing undispensed prescription
drugs. A list of the authorized personnel having such access shall
be in the pharmacy's policy and procedure manual.
(H) Storage requirements and beyond-use dating.
(i) Storage requirements. All drugs shall be stored
at the proper temperature and conditions, as defined in the USP/NF
and in §291.15 of this title (relating to Storage of Drugs).
(ii) Beyond-use dating.
(I) Beyond-use dates for compounded sterile preparations
shall be assigned based on professional experience, which shall include
careful interpretation of appropriate information sources for the
same or similar formulations.
(II) Beyond-use dates for compounded sterile preparations
that are prepared strictly in accordance with manufacturers' product
labeling must be those specified in that labeling, or from appropriate
literature sources or direct testing.
(III) When assigning a beyond-use date, compounding
personnel shall consult and apply drug-specific and general stability
documentation and literature where available, and they should consider
the nature of the drug and its degradation mechanism, the container
in which it is packaged, the expected storage conditions, and the
intended duration of therapy.
(IV) The sterility and storage and stability beyond-use
date for attached and activated container pairs of drug products for
intravascular administration shall be applied as indicated by the
manufacturer.
(7) Primary engineering control device. The pharmacy
shall prepare sterile preparations in a primary engineering control
device (PEC), such as a laminar air flow hood, biological safety cabinet,
compounding aseptic isolator (CAI), or compounding aseptic containment
isolator (CACI) which is capable of maintaining at least ISO Class
5 conditions for 0.5 micrometer particles while compounding sterile
preparations.
(A) Laminar air flow hood. If the pharmacy is using
a laminar air flow hood as its PEC, the laminar air flow hood shall:
(i) be located in the buffer area and placed in the
buffer area in a manner as to avoid conditions that could adversely
affect its operation such as strong air currents from opened doors,
personnel traffic, or air streams from the heating, ventilating and
air condition system;
(ii) be certified for operational efficiency using
certification procedures, such as those outlined in the Certification
Guide for Sterile Compounding Facilities (CAG-003-2006), which shall
be performed by a qualified independent individual no less than every
six months and whenever the device or room is relocated or altered
or major service to the facility is performed;
(iii) have pre-filters inspected periodically and replaced
as needed, in accordance with written policies and procedures and
the manufacturer's specification, and the inspection and/or replacement
date documented; and
(iv) be located in a buffer area that has a minimum
differential positive pressure of 0.02 to 0.05 inches water column.
A buffer area that is not physically separated from the ante-area
shall employ the principle of displacement airflow as defined in Chapter
797, Pharmaceutical Compounding--Sterile Preparations, of the USP/NF,
with limited access to personnel.
(B) Biological safety cabinet.
Cont'd... |
