MEDIA
Prepare media for the tests as described below, or dehydrated formulations
may be used provided that, when reconstituted as directed by the manufacturer
or distributor, they meet the requirements of the Growth Promotion Test of
Aerobes, Anaerobes, and Fungi. Media are sterilized using a validated process.
The following culture media have been found to be suitable for the test for
sterility. Fluid Thioglycollate Medium is primarily intended for the culture
of anaerobic bacteria. However, it will also detect aerobic bacteria. Soybean–
Casein Digest Medium is suitable for the culture of both fungi and aerobic
bacteria.
Fluid Thioglycollate Medium
L-Cystine 0.5 g
Sodium Chloride 2.5 g
Dextrose (C6H12O6·H2O) 5.5/5.0 g
Agar, granulated (moisture content not
exceeding 15%) 0.75 g
Yeast Extract (water-soluble) 5.0 g
Pancreatic Digest of Casein 15.0 g
Sodium Thioglycollate 0.5 g
or Thioglycolic Acid 0.3 mL
Resazurin Sodium Solution (1 in 1000),
freshly prepared 1.0 mL
Purified Water 1000 mL
Mix the L-cystine, sodium chloride, dextrose, yeast extract, and
pancreatic digest of casein with the purified water, and heat until solution
is effected. Dissolve the sodium thioglycollate or thioglycolic acid in the
solution and, if necessary, add 1 N sodium hydroxide so that, after
sterilization, the solution will have a pH of 7.1 ± 0.2. If filtration is
necessary, heat the solution again without boiling, and filter while hot
through moistened filter paper. Add the resazurin sodium solution, mix, and
place the medium in suitable vessels that provide a ratio of surface to depth
of medium such that not more than the upper half of the medium has undergone
a color change indicative of oxygen uptake at the end of the incubation
period. Sterilize using a validated process. If the medium is stored, store at
a temperature between 2 and 25 in a sterile, airtight container. If more than
the upper one-third of the medium has acquired a pink color, the medium may be
restored once by heating the containers in a water-bath or in free-flowing
steam until the pink color disappears and by cooling quickly, taking care to
prevent the introduction of nonsterile air into the container.
Fluid Thioglycollate Medium is to be incubated at 32.5 ± 2.5.
Alternative Thioglycollate Medium
Prepare a mixture having the same composition as that of the Fluid
Thioglycollate Medium, but omitting the agar and the resazurin sodium
solution, sterilize as directed above, and allow to cool prior to use. The pH
after sterilization is 7.1 ± 0.2. Incubate under anaerobic conditions for the
duration of the incubation period.
Alternative Fluid Thioglycollate Medium is to be incubated at 32.5 ± 2.5.
Soybean–Casein Digest Medium
Pancreatic Digest of Casein 17.0 g
Papaic Digest of Soybean Meal 3.0 g
Sodium Chloride 5.0 g
Dibasic Potassium Phosphate 2.5 g
Dextrose (C6H12O6·H2O) 2.5/2.3 g
Purified Water 1000 mL
Dissolve the solids in the Purified Water, heating slightly to effect a
solution. Cool the solution to room temperature, and adjust the pH with 1 N
sodium hydroxide so that, after sterilization, it will have a pH of 7.3 ±
0.2. Filter, if necessary to clarify, dispense into suitable containers, and
sterilize using a validated procedure. Store at a temperature between 2 and 25
in a sterile well-closed container, unless it is intended for immediate use.
Soybean–Casein Digest Medium is to be incubated at 22.5 ± 2.5.
Media for Penicillins or Cephalosporins
Where sterility test media are to be used in the Direct Inoculation of
the Culture Medium method under Test for Sterility of the Product to be
Examined, modify the preparation of Fluid Thioglycollate Medium and the
Soybean–Casein Digest Medium as follows. To the containers of each medium,
transfer aseptically a quantity of b-lactamase sufficient to inactivate the
amount of antibiotic in the specimen under test. Determine the quantity of b-
lactamase required to inactivate the antibiotic by using a b-lactamase
preparation that has been assayed previously for its penicillin- or
cephalosporin-inactivating power. [NOTE—Supplemented b-lactamase media can
also be used in the membrane filtration test.]
Alternatively (in an area completely separate from that used for sterility
testing), confirm that an appropriate amount of b-lactamase is incorporated
into the medium, following either method under Validation Test, using less
than 100 colony-forming units (cfu) of Staphylococcus aureus (see Table 1) as
the challenge. Typical microbial growth of the inoculated culture must be
observed as a confirmation that the b-lactamase concentration is appropriate.
Table 1. Strains of the Test Microorganisms Suitable for Use in the Growth
Promotion Test and the Validation Test
Aerobic bacteria
Staphylococcus aureus1 ATCC 6538, CIP 4.83, NCTC 10788, NCIMB 9518
Bacillus subtilis ATCC 6633, CIP 52.62, NCIMB 8054
Pseudomonas aeruginosa2 ATCC 9027, NCIMB 8626, CIP 82.118
Anaerobic bacterium
Clostridium sporogenes3 ATCC 19404, CIP 79.3, NCTC 532 or ATCC 11437
Fungi
Candida albicans ATCC 10231, IP 48.72, NCPF 3179
Aspergillus niger ATCC 16404, IP 1431.83, IMI 149007
1 、 An alternative to Staphylococcus aureus is Bacillus subtilis (ATCC
6633).
2 、 An alternative microorganism is Micrococcus luteus (Kocuria rhizophila),
ATCC 9341.
3 、 An alternative to Clostridium sporogenes, when a nonspore-forming
microorganism is desired, is Bacetroides vulgatus (ATCC 8482).
[NOTE—Seed-lot culture maintenance techniques (seed-lot systems) are used so
that the viable microorganisms used for inoculation are not more than five
passages removed from the original master seed lot.]
Suitability Tests
The media used comply with the following tests, carried out before, or in
parallel, with the test on the product to be examined.
STERILITY
Confirm the sterility of each sterilized batch of medium by incubating a
portion of the media at the specified incubation temperature for 14 days. No
growth of microorganisms occurs.
GROWTH PROMOTION TEST OF AEROBES, ANAEROBES, AND FUNGI
Test each lot of of ready-prepared medium and each batch of medium prepared
either from dehydrated medium or from ingredients 1 . Suitable strains of
microorganisms are indicated in Table 1.
Inoculate portions of Fluid Thioglycollate Medium with a small number (not
more than 100 cfu) of the following microorganisms, using a separate portion
of medium for each of the following species of microorganism: Clostridium
sporogenes, Pseudomonas aeruginosa, and Staphylococcus aureus. Inoculate
portions of Alternative Fluid Thioglycollate Medium with a small number (not
more than 100 cfu) of Clostridium sporogenes. Inoculate portions of Soybean–
Casein Digest Medium with a small number (not more than 100 cfu) of the
following microorganisms, using a separate portion of medium for each of the
following species of microorganism: Aspergillus niger, Bacillus subtilis, and
Candida albicans. Incubate for not more than 3 days in the case of bacteria
and not more than 5 days in the case of fungi.
The media are suitable if a clearly visible growth of the microorganisms
occurs.
STORAGE
If prepared media are stored in unsealed containers, they can be used for 1
month, provided that they are tested for growth promotion within 2 weeks of
the time of use and that color indicator requirements are met. If stored in
tight containers, the media can be used for 1 year, provided that they are
tested for growth promotion within 3 months of the time of use and that the
color indicator requirements are met.
DILUTING AND RINSING FLUIDS FOR MEMBRANE FILTRATION
Fluid A
PREPARATION
Dissolve 1 g of peptic digest of animal tissue in water to make 1 L, filter
or centrifuge to clarify, if necessary, and adjust to a pH of 7.1 ± 0.2.
Dispense into containers, and sterilize using a validated process.
PREPARATION FOR PENICILLINS OR CEPHALOSPORINS
Aseptically add to the above Preparation, if necessary, a quantity of
sterile b-lactamase sufficient to inactivate any residual antibiotic activity
on the membranes after the solution of the test specimen has been filtered
(see Media for Penicillins or Cephalosporins).
Fluid D
To each L of Fluid A add 1 mL of polysorbate 80, adjust to a pH of 7.1 ±
0.2, dispense into containers, and sterilize using a validated process. Use
this fluid for articles containing lecithin or oil, or for devices labeled as
“sterile pathway.”
Fluid K
Dissolve 5.0 g of peptic digest of animal tissue, 3.0 g of beef extract,
and 10.0 g of polysorbate 80 in water to make 1 L. Adjust the pH to obtain,
after sterilization, a pH of 6.9 ± 0.2. Dispense into containers, and
sterilize using a validated process.
VALIDATION TEST
Carry out a test as described below under Test for Sterility of the Product
to be Examined using exactly the same methods, except for the following
modifications.
Membrane Filtration
After transferring the content of the container or containers to be tested
(not more than 100 cfu) to the final portion of sterile diluent used to rinse
the filter.
Direct Inoculation
After transferring the contents of the container or containers to be
tested (for catgut and other surgical sutures for veterinary use: strands) to
the culture medium, add an inoculum of a small number of viable microorganisms
(not more than 100 cfu) to the medium.
In both cases use the same microorganisms as those described above under
Growth Promotion Test of Aerobes, Anaerobes, and Fungi. Perform a growth
promotion test as a positive control. Incubate all the containers containing
medium for not more than 5 days.
If clearly visible growth of microorganisms is obtained after the
incubation, visually comparable to that in the control vessel without product,
either the product possesses no antimicrobial activity under the conditions
of the test or such activity has been satisfactorily eliminated. The test for
sterility may then be carried out without further modification.
If clearly visible growth is not obtained in the presence of the product to
be tested, visually comparable to that in the control vessels without
product, the product possesses antimicrobial activity that has not been
satisfactorily eliminated under the conditions of the test. Modify the
conditions in order to eliminate the antimicrobial activity, and repeat the
validation test.
This validation is performed (a) when the test for sterility has to be
carried out on a new product; and (b) whenever there is a change in the
experimental conditions of the test. The validation may be performed
simultaneously with the Test for Sterility of the Product to be Examined.
TEST FOR STERILITY OF THE PRODUCT TO BE EXAMINED
Number of Articles to Be Tested
Unless otherwise specified elsewhere in this chapter or in the individual
monograph, test the number of articles specified in Table 3. If the contents
of each article are of sufficient quantity (see Table 2), they may be divided
so that equal appropriate portions are added to each of the specified media.
[NOTE—Perform sterility testing employing two or more of the specified
media.] If each article does not contain sufficient quantities for each
medium, use twice the number of articles indicated in Table 3.
Table 2. Minimum Quantity to be Used for Each Medium
Quantity per Container Minimum Quantity to be Used (unless otherwise
justified and authorized)
Liquids (other than anitbiotics)
Less than 1 mL The whole contents of each container
1–40 mL Half the contents of each container, but not less than 1 mL
Greater than 40 mL, and not greater than 100 mL 20 mL
Greater than 100 mL 10% of the contents of the container, but not less
than 20 mL
Antibiotic liquids 1 mL
Other preparations soluble in water or in isopropyl myristate The whole
contents of each container to provide not less than 200 mg
Insoluble preparations, creams, and ointments to be suspended or emulsified
Use the contents of each container to provide not less than 200 mg
Solids
Less than 50 mg： The whole contents of each container 50 mg or more, but
less than 300 mg Half the contents of each container, but not less than 50 mg
300 mg–5 g 150 mg ，Greater than 5 g 500 mg
Devices
Catgut and other surgical sutures for veterinary use 3 sections of a
strand (each 30-cm long)
Surgical dressing/cotton/gauze (in packages) 100 mg per package
Sutures and other individually packaged single-use material The whole
device
Other medical devices The whole device, cut into pieces or disassembled
Table 3. Minimum Number of Articles to be Tested in Relation to the Number of
Articles in the Batch
Number of Items in the Batch Minimum Number of Items to be Tested for Each
Medium (unless otherwise justified and authorized)*
Parenteral preparations
Not more than 100 containers 10% or 4 containers, whichever is the greater
More than 100 but not more than 500 containers 10 containers
More than 500 containers 2% or 20 containers, whichever is less
For large-volume parenterals 2% or 10 containers, whichever is less
Antibiotic solids
Pharmacy bulk packages (<5 g) 20 containers
Pharmacy bulk packages (³5 g) 6 containers
Bulks and blends See Bulk solid products
Ophthalmic and other noninjectable preparations
Not more than 200 containers 5% or 2 containers, whichever is the greater
More than 200 containers 10 containers
If the product is presented in the form of single-dose containers, apply the
scheme shown above for preparations for parenteral use.
Devices
Catgut and other surgical sutures for veterinary use 2 or5packages,whichever
is the greater,up to a maximum total of 20 packages .Not more than 100
articles 10% or 4 articles, whichever is greater .More than 100, but not more
than 500 articles 10 articles .More than 500 articles 2% or 20 articles,
whichever is less
Bulk solid products
Up to 4 containers Each container
More than 4 containers, but not more than 50 containers 20% or 4
containers, whichever is greater
More than 50 containers 2% or 10 containers, whichever is greater
If the contents of one container are enough to inoculate the two media,
this column gives the number of containers needed for both the media
together.
The test may be carried out using the technique of Membrane Filtration or
by Direct Inoculation of the Culture Medium with the product to be examined.
Appropriate negative controls are included. The technique of membrane
filtration is used whenever the nature of the product permits; that is, for
filterable aqueous preparations, for alcoholic or oily preparations, and for
preparations miscible with, or soluble in, aqueous or oily solvents, provided
these solvents do not have an antimicrobial effect in the conditions of the test.
Membrane Filtration
Use membrane filters having a nominal pore size not greater than 0.45 µm
whose effectiveness to retain microorganisms has been established. Cellulose
nitrate filters, for example, are used for aqueous, oily, and weakly alcoholic
solutions; and cellulose acetate filters, for example, are used for strongly
alcoholic solutions. Specially adapted filters may be needed for certain
products (e.g., for antibiotics).
The technique described below assumes that membranes about 50 mm in
diameter will be used. If filters of a different diameter are used, the
volumes of the dilutions and the washings should be adjusted accordingly. The
filtration apparatus and membrane are sterilized by appropriate means. The
apparatus is designed so that the solution to be examined can be introduced
and filtered under aseptic conditions: it permits the aseptic removal of the
membrane for transfer to the medium, or it is suitable for carrying out the
incubation after adding the medium to the apparatus itself.
AQUEOUS SOLUTIONS
If appropriate, transfer a small quantity of a suitable, sterile diluent
such as Fluid A (see Diluting and Rinsing Fluids for Membrane Filtration)
onto the membrane in the apparatus and filter. The diluent may contain
suitable neutralizing substances and/or appropriate inactivating substances,
for example, in the case of antibiotics.
Transfer the contents of the container or containers to be tested to the
membrane or membranes, if necessary, after diluting to the volume used in the
Validation Test with the chosen sterile diluent, but using not less than the
quantities of the product to be examined prescribed in Tables 2 and 3. Filter
immediately. If the product has antimicrobial properties, wash the membrane
not less than three times by filtering through it each time the volume of the
chosen sterile diluent used in the Validation Test. Do not exceed a washing
cycle of 5 times 200 mL, even if during validation it has been demonstrated
that such a cycle does not fully eliminate the antimicrobial activity.
Transfer the whole membrane to the culture medium or cut it aseptically
into two equal parts, and transfer one half to each of two suitable media. Use
the same volume of each medium as in the Validation Test. Alternatively,
transfer the medium onto the membrane in the apparatus. Incubate the media for
not less than 14 days.
SOLUBLE SOLIDS (other than antibiotics)
Use for each medium not less than the quantity prescribed in Tables 2 and 3
of the product dissolved in a suitable solvent, such as Fluid A (Diluting and
Rinsing Fluids for Membrane Filtration), and proceed with the test as
described above for Aqueous Solutions using a membrane appropriate to the
chosen solvent.
OILS AND OILY SOLUTIONS
Use for each medium not less than the quantity of the product prescribed in
Tables 2 and 3. Oils and oily solutions of sufficiently low viscosity may be
filtered without dilution through a dry membrane. Viscous oils may be diluted
as necessary with a suitable sterile diluent such as isopropyl myristate shown
not to have antimicrobial activity in the conditions of the test. Allow the
oil to penetrate the membrane by its own weight, and then filter, applying the
pressure or suction gradually. Wash the membrane at least three times by
filtering through it each time about 100 mL of a suitable sterile solution
such as Fluid A (see Diluting and Rinsing Fluids for Membrane Filtration)
containing a suitable emulsifying agent at a concentration shown to be
appropriate in the validation of the test, for example polysorbate 80 at a
concentration of 10 g per L (Fluid K). Transfer the membrane or membranes to
the culture medium or media, or vice versa, as described above for Aqueous
Solutions, and incubate at the same temperatures and for the same times.
OINTMENTS AND CREAMS
Use for each medium not less than the quantities of the product prescribed
in Tables 2 and 3. Ointments in a fatty base and emulsions of the water-in-oil
type may be diluted to 1% in isopropyl myristate as described above, by
heating, if necessary, to not more than 40. In exceptional cases it may be
necessary to heat to not more than 44. Filter as rapidly as possible, and
proceed as described above for Oils and Oily Solutions.
PREFILLED SYRINGES
For prefilled syringes without attached sterile needles, expel the contents
of each syringe into one or two separate membrane filter funnels or into
separate pooling vessels prior to transfer. If a separate sterile needle is
attached, directly expel the syringe contents as indicated above, and proceed
as directed for Aqueous Solutions. Test the sterility of the needle, using
Direct Inoculation under Validation Test.
SOLIDS FOR INJECTION OTHER THAN ANTIBIOTICS
Constitute the test articles as directed on the label, and proceed as
directed for Aqueous Solutions or Oils and Oily Solutions, whichever applies.
[NOTE—If necessary, excess diluent can be added to aid in the constitution
and filtration of the constituted test article.]
ANTIBIOTIC SOLIDS FOR INJECTION
Pharmacy Bulk Packages, < 5 g— From each of 20 containers, aseptically
transfer about 300 mg of solids, into a sterile 500-mL conical flask, dissolve
in about 200 mL of Fluid A (see Diluting and Rinsing Fluids for Membrane
Filtration), and mix; or constitute, as directed in the labeling, each of 20
containers and transfer a quantity of liquid or suspension, equivalent to
about 300 mg of solids, into a sterile 500-mL conical flask, dissolve in about
200 mL of Fluid A, and mix. Proceed as directed for Aqueous Solutions or Oils
and Oily Solutions, whichever applies.
Pharmacy Bulk Packages, ³5 g— From each of 6 containers, aseptically
transfer about 1 g of solids into a sterile 500-mL conical flask, dissolve in
about 200 mL of Fluid A, and mix; or constitute, as directed in the labeling,
each of 6 containers and transfer a quantity of liquid, equivalent to about 1
g of solids, into a sterile 500-mL conical flask, dissolve in about 200 mL of
Fluid A, and mix. Proceed as directed for Aqueous Solutions.
ANTIBIOTIC SOLIDS, BULKS, AND BLENDS
Aseptically remove a sufficient quantity of solids from the appropriate
amount of containers (see Table 2), mix to obtain a composite, equivalent to
about 6 g of solids, and transfer to a sterile 500-mL conical flask. Dissolve
in about 200 mL of Fluid A, and mix. Proceed as directed for Aqueous Solutions.
STERILE AEROSOL PRODUCTS
For fluid products in pressurized aerosol form, freeze the containers in an
alcohol-dry ice mixture at least at –20 for about 1 hour. If feasible, allow
the propellant to escape before aseptically opening the container, and
transfer the contents to a sterile pooling vessel. Add 100 mL of Fluid D to
the pooling vessel, and mix gently. Proceed as directed for Aqueous Solutions
or Oils and Oily Solutions, whichever applies.
DEVICES WITH PATHWAYS LABELED STERILE
Aseptically pass not less than 10 pathway volumes of Fluid D through each
device tested. Collect the fluids in an appropriate sterile vessel, and
proceed as directed for Aqueous Solutions or Oils and Oily Solutions,
whichever applies.
In the case of sterile, empty syringes, draw sterile diluent into the
barrel through the sterile needle, if attached, or through a sterile needle
attached for the purpose of the test, and express the contents into a sterile
pooling vessel. Proceed as directed above.
Direct Inoculation of the Culture Medium
Transfer the quantity of the preparation to be examined prescribed in
Tables 2 and 3 directly into the culture medium so that the volume of the
product is not more than 10% of the volume of the medium, unless otherwise
prescribed.
If the product to be examined has antimicrobial activity, carry out the
test after neutralizing this with a suitable neutralizing substance or by
dilution in a sufficient quantity of culture medium. When it is necessary to
use a large volume of the product, it may be preferable to use a concentrated
culture medium prepared in such a way that it takes into account the
subsequent dilution. Where appropriate, the concentrated medium may be added
directly to the product in its container.
OILY LIQUIDS
Use media to which have been added a suitable emulsifying agent at a
concentration shown to be appropriate in the validation of the test, for
example polysorbate 80 at a concentration of 10 g per liter.
OINTMENTS AND CREAMS
Prepare by diluting to about 1 in 10 by emulsifying with the chosen
emulsifying agent in a suitable sterile diluent such as Fluid A (see Diluting
and Rinsing Fluids for Membrane Filtration). Transfer the diluted product to a
medium not containing an emulsifying agent.
Incubate the inoculated media for not less than 14 days. Observe the
cultures several times during the incubation period. Shake cultures containing
oily products gently each day. However, when thioglycollate medium or other
similar medium is used for the detection of anaerobic microorganisms, keep
shaking or mixing to a minimum in order to maintain anaerobic conditions.
CATGUT AND OTHER SURGICAL SUTURES FOR VETERINARIAN USE
Use for each medium not less than the quantities of the product prescribed in
Tables 2 and 3. Open the sealed package using aseptic precautions, and remove
three sections of the strand for each culture medium. Carry out the test on
three sections, each 30-cm long, which have been cut off from the beginning,
the center, and the end of the strand. Use whole strands from freshly opened
cassette packs. Transfer each section of the strand to the selected medium.
Use sufficient medium to cover adequately the material to be tested (20 mL to 150 mL).
SOLIDS
Transfer a quantity of the product in the form of a dry solid (or prepare
a suspension of the product by adding sterile diluent to the immediate
container), corresponding to not less than the quantity indicated in Tables 2
and 3. Transfer the material so obtained to 200 mL of Fluid Thioglycollate
Medium, and mix. Similarly, transfer the same quantity to 200 mL of Soybean–
Casein Digest Medium, and mix. Proceed as directed above.
PURIFIED COTTON, GAUZE, SURGICAL DRESSINGS, AND RELATED ARTICLES
From each package of cotton, rolled gauze bandage, or large surgical
dressings being tested, aseptically remove two or more portions of 100- to 500-
mg each from the innermost part of the sample. From individually packaged,
single-use materials, aseptically remove the entire article. Immerse the
portions or article in each medium, and proceed as directed above.
STERILE DEVICES
Articles can be immersed intact or disassembled. To ensure that device
pathways are also in contact with the media, immerse the appropriate number of
units per medium in a volume of medium sufficient to immerse the device
completely, and proceed as directed above. For extremely large devices,
immerse those portions of the device that are to come into contact with the
patient in a volume of medium sufficient to achieve complete immersion of
those portions.
For catheters where the inside lumen and outside are required to be sterile,
either cut them into pieces such that the medium is in contact with the entire
lumen or fill the lumen with medium, and then immerse the intact unit.
OBSERVATION AND INTERPRETATION OF RESULTS
At intervals during the incubation period and at its conclusion, examine
the media for macroscopic evidence of microbial growth. If the material being
tested renders the medium turbid so that the presence or absence of microbial
growth cannot be readily determined by visual examination, 14 days after the
beginning of incubation transfer portions (each not less than 1 mL) of the
medium to fresh vessels of the same medium, and then incubate the original and
transfer vessels for not less than 4 days.
If no evidence of microbial growth is found, the product to be examined
complies with the test for sterility. If evidence of microbial growth is
found, the product to be examined does not comply with the test for sterility,
unless it can be clearly demonstrated that the test was invalid for causes
unrelated to the product to be examined. The test may be considered invalid
only if one or more of the following conditions are fulfilled:
The data of the microbiological monitoring of the sterility testing facility
show a fault.
A review of the testing procedure used during the test in question reveals
a fault.
Microbial growth is found in the negative controls.
After determination of the identity of the microorganisms isolated from the
test, the growth of this species (or these species) may be ascribed
unequivocally to faults with respect to the material and or the technique used
in conducting the sterility test procedure.
If the test is declared to be invalid, it is repeated with the same number
of units as in the original test. If no evidence of microbial growth is found
in the repeat test, the product examined complies with the test for sterility.
If microbial growth is found in the repeat test, the product examined does
not comply with the test for sterility.
APPLICATION OF THE TEST TO PARENTERAL PREPARATIONS, OPHTHALMIC, AND OTHER
NONINJECTABLE PREPARATIONS REQUIRED TO COMPLY WITH THE TEST FOR STERILITY
When using the technique of membrane filtration, use, whenever possible,
the whole contents of the container, but not less than the quantities
indicated in Tables 2 and 3, diluting where necessary to about 100 mL with a
suitable sterile solution, such as Fluid A (see Diluting and Rinsing Fluids
for Membrane Filtration).
When using the technique of direct inoculation of media, use the quantities
shown in Tables 2 and 3, unless otherwise justified and authorized. The tests
for bacterial and fungal sterility are carried out on the same sample of the
product to be examined. When the volume or the quantity in a single container
is insufficient to carry out the tests, the contents of two or more containers
are used to inoculate the different media.
In appropriate cases, periodic testing of the different batches prepared
from the same lot of dehydrated medium is acceptable.
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