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a sterile 10-milliliter syringe and 18-gauge needle combination is
used to exchange two 5-milliliter aliquots of medium from one container
to the other container in the pair. For example, after a 5-milliliter
aliquot from the first container is added to the second container
in the pair, the second container is agitated for 10 seconds, then
a 5-milliliter aliquot is removed and returned to the first container
in the pair. The first container is then agitated for 10 seconds,
and the next 5-milliliter aliquot is transferred from it back to the
second container in the pair. Following the two 5-milliliter aliquot
exchanges in each pair of containers, a 5-milliliter aliquot of medium
from each container is aseptically injected into a sealed, empty,
sterile 10-milliliter clear vial, using a sterile 10-milliliter syringe
and vented needle. 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.
(iii) High risk level preparations.
(I) Procedures for high-risk level compounded sterile
preparations include all those for low-risk level compounded sterile
preparations. In addition, a media-fill test that represents high-risk
level compounding is performed twice a year by each person authorized
to compound high-risk level compounded sterile preparations.
(II) Example of a Media-Fill Test Procedure for Compounded
Sterile Preparations Sterilized by Filtration. This test, or an equivalent
test, is performed under conditions that closely simulate the most
challenging or stressful conditions encountered when compounding high-risk
level compounded sterile preparations. Note: Sterility tests for autoclaved
compounded sterile preparations are not required unless they are prepared
in batches of more than 25 units. This test is completed without interruption
in the following sequence:
(-a-) Dissolve 3 grams of non-sterile commercially
available fluid culture media in 100 milliliters of non-bacteriostatic
water to make a 3% non-sterile solution.
(-b-) Draw 25 milliliters of the medium into each of
three 30-milliliter sterile syringes. Transfer 5 milliliters from
each syringe into separate sterile 10-milliliter vials. These vials
are the positive controls to generate exponential microbial growth,
which is indicated by visible turbidity upon incubation.
(-c-) Under aseptic conditions and using aseptic techniques,
affix a sterile 0.2-micron porosity filter unit and a 20-gauge needle
to each syringe. Inject the next 10 milliliters from each syringe
into three separate 10-milliliter sterile vials. Repeat the process
for three more vials. Label all vials, affix sterile adhesive seals
to the closure of the nine vials, and incubate them at 20 to 35 degrees
Celsius for a minimum of 14 days. Inspect for microbial growth over
14 days as described in Chapter 797 Pharmaceutical Compounding--Sterile
Preparations, of the USP/NF.
(III) Filter Integrity Testing. Filters need to undergo
testing to evaluate the integrity of filters used to sterilize high-risk
preparations, such as Bubble Point Testing or comparable filter integrity
testing. Such testing is not a replacement for sterility testing and
shall not be interpreted as such. Such test shall be performed after
a sterilization procedure on all filters used to sterilize each high-risk
preparation or batch preparation and the results documented. The results
should be compared with the filter manufacturer's specification for
the specific filter used. If a filter fails the integrity test, the
preparation or batch must be sterilized again using new unused filters.
(B) Finished preparation release checks and tests.
(i) All high-risk level compounded sterile preparations
that are prepared in groups of more than 25 identical individual single-dose
packages (such as ampules, bags, syringes, and vials), or in multiple
dose vials for administration to multiple patients, or are exposed
longer than 12 hours at 2 - 8 degrees Celsius and longer than six
hours at warmer than 8 degrees Celsius before they are sterilized
shall be tested to ensure they are sterile and do not contain excessive
bacterial endotoxins as specified in Chapter 71, Sterility Tests of
the USP/NF before being dispensed or administered.
(ii) All compounded sterile preparations, except for
sterile radiopharmaceuticals, that are intended to be solutions must
be visually examined for the presence of particulate matter and not
administered or dispensed when such matter is observed.
(iii) The prescription drug and medication orders,
written compounding procedure, preparation records, and expended materials
used to make compounded sterile preparations at all contamination
risk levels shall be inspected for accuracy of correct identities
and amounts of ingredients, aseptic mixing and sterilization, packaging,
labeling, and expected physical appearance before they are dispensed
or administered.
(iv) Written procedures for checking compounding accuracy
shall be followed for every compounded sterile preparation during
preparation, in accordance with pharmacy's policies and procedures,
and immediately prior to release, including label accuracy and the
accuracy of the addition of all drug products or ingredients used
to prepare the finished preparation and their volumes or quantities.
A pharmacist shall ensure that components used in compounding are
accurately weighed, measured, or subdivided as appropriate to conform
to the formula being prepared.
(C) Environmental Testing.
(i) Viable and nonviable environmental sampling testing.
Environmental sampling shall occur, at a minimum, every six months
as part of a comprehensive quality management program and under any
of the following conditions:
(I) as part of the commissioning and certification
of new facilities and equipment;
(II) following any servicing of facilities and equipment;
(III) as part of the re-certification of facilities
and equipment;
(IV) in response to identified problems with end products
or staff technique; or
(V) in response to issues with compounded sterile preparations,
observed compounding personnel work practices, or patient-related
infections (where the compounded sterile preparation is being considered
as a potential source of the infection).
(ii) Total particle counts. Certification that each
ISO classified area (e.g., ISO Class 5, 7, and 8), is within established
guidelines shall be performed no less than every six months and whenever
the equipment is relocated or the physical structure of the buffer
area or ante-area has been altered. All certification records shall
be maintained and reviewed to ensure that the controlled environments
comply with the proper air cleanliness, room pressures, and air changes
per hour. These certification records must include acceptance criteria
and be made available upon inspection by the Board. Testing shall
be performed by qualified operators using current, state-of-the-art
equipment, with results of the following:
(I) ISO Class 5 - not more than 3520 particles 0.5
micrometer and larger size per cubic meter of air;
(II) ISO Class 7 - not more than 352,000 particles
of 0.5 micrometer and larger size per cubic meter of air for any buffer
area; and
(III) ISO Class 8 - not more than 3,520,000 particles
of 0.5 micrometer and larger size per cubic meter of air for any ante-area.
(iii) Pressure differential monitoring. A pressure
gauge or velocity meter shall be installed to monitor the pressure
differential or airflow between the buffer area and the ante-area
and between the ante-area and the general environment outside the
compounding area. The results shall be reviewed and documented on
a log at least every work shift (minimum frequency shall be at least
daily) or by a continuous recording device. The pressure between the
ISO Class 7 or ISO Class 8 and the general pharmacy area shall not
be less than 0.02 inch water column.
(iv) Sampling plan. An appropriate environmental sampling
plan shall be developed for airborne viable particles based on a risk
assessment of compounding activities performed. Selected sampling
sites shall include locations within each ISO Class 5 environment
and in the ISO Class 7 and 8 areas and in the segregated compounding
areas at greatest risk of contamination. The plan shall include sample
location, method of collection, frequency of sampling, volume of air
sampled, and time of day as related to activity in the compounding
area and action levels.
(v) Viable air sampling. Evaluation of airborne microorganisms
using volumetric collection methods in the controlled air environments
shall be performed by properly trained individuals for all compounding
risk levels. For low-, medium-, and high-risk level compounding, air
sampling shall be performed at locations that are prone to contamination
during compounding activities and during other activities such as
staging, labeling, gowning, and cleaning. Locations shall include
zones of air backwash turbulence Cont'd... |
