聽聽聽聽聽聽聽聽聽
聽聽聽聽MEDIA聽
聽聽聽聽Prepare聽media聽for聽the聽tests聽as聽described聽below,聽or聽dehydrated聽formulations聽
may聽be聽used聽provided聽that,聽when聽reconstituted聽as聽directed聽by聽the聽manufacturer聽
or聽distributor,聽they聽meet聽the聽requirements聽of聽the聽Growth聽Promotion聽Test聽of聽
Aerobes,聽Anaerobes,聽and聽Fungi.聽Media聽are聽sterilized聽using聽a聽validated聽process.
聽
The聽following聽culture聽media聽have聽been聽found聽to聽be聽suitable聽for聽the聽test聽for
聽sterility.聽Fluid聽Thioglycollate聽Medium聽is聽primarily聽intended聽for聽the聽culture聽
of聽anaerobic聽bacteria.聽However,聽it聽will聽also聽detect聽aerobic聽bacteria.聽Soybean–
Casein聽Digest聽Medium聽is聽suitable聽for聽the聽culture聽of聽both聽fungi聽and聽aerobic聽
bacteria.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Fluid聽Thioglycollate聽Medium聽
聽
聽聽聽聽聽聽聽聽聽聽聽聽聽L-Cystine聽0.5聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Sodium聽Chloride聽2.5聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Dextrose聽(C6H12O6·H2O)聽5.5/5.0聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Agar,聽granulated聽(moisture聽content聽not
聽聽聽聽聽聽聽聽聽聽聽聽聽exceeding聽15%)聽0.75聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Yeast聽Extract聽(water-soluble)聽5.0聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Pancreatic聽Digest聽of聽Casein聽15.0聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Sodium聽Thioglycollate聽0.5聽g聽
聽聽聽聽聽聽聽聽聽聽聽聽聽or聽Thioglycolic聽Acid聽0.3聽mL聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Resazurin聽Sodium聽Solution聽(1聽in聽1000),
聽聽聽聽聽聽聽聽聽聽聽聽聽freshly聽prepared聽1.0聽mL聽
聽聽聽聽聽聽聽聽聽聽聽聽聽Purified聽Water聽1000聽mL聽
聽聽聽聽Mix聽the聽L-cystine,聽sodium聽chloride,聽dextrose,聽yeast聽extract,聽and聽
pancreatic聽digest聽of聽casein聽with聽the聽purified聽water,聽and聽heat聽until聽solution聽
is聽effected.聽Dissolve聽the聽sodium聽thioglycollate聽or聽thioglycolic聽acid聽in聽the聽
solution聽and,聽if聽necessary,聽add聽1聽N聽sodium聽hydroxide聽so聽that,聽after聽
sterilization,聽the聽solution聽will聽have聽a聽pH聽of聽7.1聽±聽0.2.聽If聽filtration聽is聽
necessary,聽heat聽the聽solution聽again聽without聽boiling,聽and聽filter聽while聽hot聽
through聽moistened聽filter聽paper.聽Add聽the聽resazurin聽sodium聽solution,聽mix,聽and聽
place聽the聽medium聽in聽suitable聽vessels聽that聽provide聽a聽ratio聽of聽surface聽to聽depth
聽of聽medium聽such聽that聽not聽more聽than聽the聽upper聽half聽of聽the聽medium聽has聽undergone
聽a聽color聽change聽indicative聽of聽oxygen聽uptake聽at聽the聽end聽of聽the聽incubation聽
period.聽Sterilize聽using聽a聽validated聽process.聽If聽the聽medium聽is聽stored,聽store聽at
聽a聽temperature聽between聽2聽and聽25聽in聽a聽sterile,聽airtight聽container.聽If聽more聽than聽
the聽upper聽one-third聽of聽the聽medium聽has聽acquired聽a聽pink聽color,聽the聽medium聽may聽be
聽restored聽once聽by聽heating聽the聽containers聽in聽a聽water-bath聽or聽in聽free-flowing聽
steam聽until聽the聽pink聽color聽disappears聽and聽by聽cooling聽quickly,聽taking聽care聽to聽
prevent聽the聽introduction聽of聽nonsterile聽air聽into聽the聽container.
聽
Fluid聽Thioglycollate聽Medium聽is聽to聽be聽incubated聽at聽32.5聽±聽2.5.聽
聽聽聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Alternative聽Thioglycollate聽Medium聽
聽聽聽聽聽Prepare聽a聽mixture聽having聽the聽same聽composition聽as聽that聽of聽the聽Fluid聽
Thioglycollate聽Medium,聽but聽omitting聽the聽agar聽and聽the聽resazurin聽sodium聽
solution,聽sterilize聽as聽directed聽above,聽and聽allow聽to聽cool聽prior聽to聽use.聽The聽pH聽
after聽sterilization聽is聽7.1聽±聽0.2.聽Incubate聽under聽anaerobic聽conditions聽for聽the聽
duration聽of聽the聽incubation聽period.聽
聽聽聽聽Alternative聽Fluid聽Thioglycollate聽Medium聽is聽to聽be聽incubated聽at聽32.5聽±聽2.5.
聽
Soybean–Casein聽Digest聽Medium聽
聽
聽聽聽聽聽聽聽聽聽Pancreatic聽Digest聽of聽Casein聽17.0聽g聽
聽聽聽聽聽聽聽聽聽Papaic聽Digest聽of聽Soybean聽Meal聽3.0聽g聽
聽聽聽聽聽聽聽聽聽Sodium聽Chloride聽5.0聽g聽
聽聽聽聽聽聽聽聽聽Dibasic聽Potassium聽Phosphate聽2.5聽g聽
聽聽聽聽聽聽聽聽聽Dextrose聽(C6H12O6·H2O)聽2.5/2.3聽g聽
聽聽聽聽聽聽聽聽聽Purified聽Water聽1000聽mL聽
聽聽聽Dissolve聽the聽solids聽in聽the聽Purified聽Water,聽heating聽slightly聽to聽effect聽a聽
solution.聽Cool聽the聽solution聽to聽room聽temperature,聽and聽adjust聽the聽pH聽with聽1聽N聽
sodium聽hydroxide聽so聽that,聽after聽sterilization,聽it聽will聽have聽a聽pH聽of聽7.3聽±聽
0.2.聽Filter,聽if聽necessary聽to聽clarify,聽dispense聽into聽suitable聽containers,聽and聽
sterilize聽using聽a聽validated聽procedure.聽Store聽at聽a聽temperature聽between聽2聽and聽25聽
in聽a聽sterile聽well-closed聽container,聽unless聽it聽is聽intended聽for聽immediate聽use.聽

Soybean–Casein聽Digest聽Medium聽is聽to聽be聽incubated聽at聽22.5聽±聽2.5.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Media聽for聽Penicillins聽or聽Cephalosporins聽
聽聽聽聽聽Where聽sterility聽test聽media聽are聽to聽be聽used聽in聽the聽Direct聽Inoculation聽of聽
the聽Culture聽Medium聽method聽under聽Test聽for聽Sterility聽of聽the聽Product聽to聽be聽
Examined,聽modify聽the聽preparation聽of聽Fluid聽Thioglycollate聽Medium聽and聽the聽
Soybean–Casein聽Digest聽Medium聽as聽follows.聽To聽the聽containers聽of聽each聽medium,
聽transfer聽aseptically聽a聽quantity聽of聽b-lactamase聽sufficient聽to聽inactivate聽the聽
amount聽of聽antibiotic聽in聽the聽specimen聽under聽test.聽Determine聽the聽quantity聽of聽b-
lactamase聽required聽to聽inactivate聽the聽antibiotic聽by聽using聽a聽b-lactamase聽

聽preparation聽that聽has聽been聽assayed聽previously聽for聽its聽penicillin-聽or聽
cephalosporin-inactivating聽power.聽[NOTE—Supplemented聽b-lactamase聽media聽can聽
also聽be聽used聽in聽the聽membrane聽filtration聽test.]聽
聽聽聽聽Alternatively聽(in聽an聽area聽completely聽separate聽from聽that聽used聽for聽sterility
聽testing),聽confirm聽that聽an聽appropriate聽amount聽of聽b-lactamase聽is聽incorporated聽
into聽the聽medium,聽following聽either聽method聽under聽Validation聽Test,聽using聽less聽
than聽100聽colony-forming聽units聽(cfu)聽of聽Staphylococcus聽aureus聽(see聽Table聽1)聽as
聽the聽challenge.聽Typical聽microbial聽growth聽of聽the聽inoculated聽culture聽must聽be聽
observed聽as聽a聽confirmation聽that聽the聽b-lactamase聽concentration聽is聽appropriate.
聽
Table聽1.聽Strains聽of聽the聽Test聽Microorganisms聽Suitable聽for聽Use聽in聽the聽Growth聽
Promotion聽Test聽and聽the聽Validation聽Test聽
聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Aerobic聽bacteria聽　聽
　聽Staphylococcus聽aureus1聽ATCC聽6538,聽CIP聽4.83,聽NCTC聽10788,聽NCIMB聽9518聽
　聽Bacillus聽subtilis聽ATCC聽6633,聽CIP聽52.62,聽NCIMB聽8054聽
　聽Pseudomonas聽aeruginosa2聽ATCC聽9027,聽NCIMB聽8626,聽CIP聽82.118聽
Anaerobic聽bacterium聽　聽
　聽Clostridium聽sporogenes3聽ATCC聽19404,聽CIP聽79.3,聽NCTC聽532聽or聽ATCC聽11437聽
Fungi聽　聽
　聽Candida聽albicans聽ATCC聽10231,聽IP聽48.72,聽NCPF聽3179聽
　聽Aspergillus聽niger聽ATCC聽16404,聽IP聽1431.83,聽IMI聽149007聽
1聽、聽An聽alternative聽to聽Staphylococcus聽aureus聽is聽Bacillus聽subtilis聽(ATCC聽
6633).聽聽
2聽、聽An聽alternative聽microorganism聽is聽Micrococcus聽luteus聽(Kocuria聽rhizophila),聽
ATCC聽9341.聽聽聽
3聽、聽An聽alternative聽to聽Clostridium聽sporogenes,聽when聽a聽nonspore-forming聽
microorganism聽is聽desired,聽is聽Bacetroides聽vulgatus聽(ATCC聽8482).聽聽聽
[NOTE—Seed-lot聽culture聽maintenance聽techniques聽(seed-lot聽systems)聽are聽used聽so聽
that聽the聽viable聽microorganisms聽used聽for聽inoculation聽are聽not聽more聽than聽five聽
passages聽removed聽from聽the聽original聽master聽seed聽lot.]聽聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Suitability聽Tests聽
聽聽聽聽The聽media聽used聽comply聽with聽the聽following聽tests,聽carried聽out聽before,聽or聽in聽
parallel,聽with聽the聽test聽on聽the聽product聽to聽be聽examined.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽STERILITY聽
聽聽聽聽Confirm聽the聽sterility聽of聽each聽sterilized聽batch聽of聽medium聽by聽incubating聽a聽
portion聽of聽the聽media聽at聽the聽specified聽incubation聽temperature聽for聽14聽days.聽No聽
growth聽of聽microorganisms聽occurs.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽GROWTH聽PROMOTION聽TEST聽OF聽AEROBES,聽ANAEROBES,聽AND聽FUNGI聽
聽聽聽Test聽each聽lot聽of聽of聽ready-prepared聽medium聽and聽each聽batch聽of聽medium聽prepared聽
either聽from聽dehydrated聽medium聽or聽from聽ingredients聽1聽.聽Suitable聽strains聽of聽
microorganisms聽are聽indicated聽in聽Table聽1.聽
聽聽聽Inoculate聽portions聽of聽Fluid聽Thioglycollate聽Medium聽with聽a聽small聽number聽(not聽
more聽than聽100聽cfu)聽of聽the聽following聽microorganisms,聽using聽a聽separate聽portion聽
of聽medium聽for聽each聽of聽the聽following聽species聽of聽microorganism:聽Clostridium聽
sporogenes,聽Pseudomonas聽aeruginosa,聽and聽Staphylococcus聽aureus.聽Inoculate聽
portions聽of聽Alternative聽Fluid聽Thioglycollate聽Medium聽with聽a聽small聽number聽(not聽
more聽than聽100聽cfu)聽of聽Clostridium聽sporogenes.聽Inoculate聽portions聽of聽Soybean–
Casein聽Digest聽Medium聽with聽a聽small聽number聽(not聽more聽than聽100聽cfu)聽of聽the聽
following聽microorganisms,聽using聽a聽separate聽portion聽of聽medium聽for聽each聽of聽the聽
following聽species聽of聽microorganism:聽Aspergillus聽niger,聽Bacillus聽subtilis,聽and聽
Candida聽albicans.聽Incubate聽for聽not聽more聽than聽3聽days聽in聽the聽case聽of聽bacteria聽
and聽not聽more聽than聽5聽days聽in聽the聽case聽of聽fungi.聽
聽聽聽聽The聽media聽are聽suitable聽if聽a聽clearly聽visible聽growth聽of聽the聽microorganisms聽
occurs.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽STORAGE聽
聽聽聽If聽prepared聽media聽are聽stored聽in聽unsealed聽containers,聽they聽can聽be聽used聽for聽1
聽month,聽provided聽that聽they聽are聽tested聽for聽growth聽promotion聽within聽2聽weeks聽of
聽the聽time聽of聽use聽and聽that聽color聽indicator聽requirements聽are聽met.聽If聽stored聽in
聽tight聽containers,聽the聽media聽can聽be聽used聽for聽1聽year,聽provided聽that聽they聽are聽
tested聽for聽growth聽promotion聽within聽3聽months聽of聽the聽time聽of聽use聽and聽that聽the聽
color聽indicator聽requirements聽are聽met.聽
聽聽聽聽聽聽聽聽聽DILUTING聽AND聽RINSING聽FLUIDS聽FOR聽MEMBRANE聽FILTRATION聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Fluid聽A聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽PREPARATION聽
聽聽聽Dissolve聽1聽g聽of聽peptic聽digest聽of聽animal聽tissue聽in聽water聽to聽make聽1聽L,聽filter聽
or聽centrifuge聽to聽clarify,聽if聽necessary,聽and聽adjust聽to聽a聽pH聽of聽7.1聽±聽0.2.聽
Dispense聽into聽containers,聽and聽sterilize聽using聽a聽validated聽process.聽
PREPARATION聽FOR聽PENICILLINS聽OR聽CEPHALOSPORINS聽
聽聽Aseptically聽add聽to聽the聽above聽Preparation,聽if聽necessary,聽a聽quantity聽of聽
sterile聽b-lactamase聽sufficient聽to聽inactivate聽any聽residual聽antibiotic聽activity
聽on聽the聽membranes聽after聽the聽solution聽of聽the聽test聽specimen聽has聽been聽filtered聽
(see聽Media聽for聽Penicillins聽or聽Cephalosporins).聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Fluid聽D聽
聽聽聽To聽each聽L聽of聽Fluid聽A聽add聽1聽mL聽of聽polysorbate聽80,聽adjust聽to聽a聽pH聽of聽7.1聽±聽
0.2,聽dispense聽into聽containers,聽and聽sterilize聽using聽a聽validated聽process.聽Use聽
this聽fluid聽for聽articles聽containing聽lecithin聽or聽oil,聽or聽for聽devices聽labeled聽as聽
“sterile聽pathway.”聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Fluid聽K聽
聽聽聽Dissolve聽5.0聽g聽of聽peptic聽digest聽of聽animal聽tissue,聽3.0聽g聽of聽beef聽extract,
聽and聽10.0聽g聽of聽polysorbate聽80聽in聽water聽to聽make聽1聽L.聽Adjust聽the聽pH聽to聽obtain,聽
after聽sterilization,聽a聽pH聽of聽6.9聽±聽0.2.聽Dispense聽into聽containers,聽and聽
sterilize聽using聽a聽validated聽process.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽VALIDATION聽TEST聽
聽聽聽Carry聽out聽a聽test聽as聽described聽below聽under聽Test聽for聽Sterility聽of聽the聽Product
聽to聽be聽Examined聽using聽exactly聽the聽same聽methods,聽except聽for聽the聽following聽
modifications.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Membrane聽Filtration聽
聽聽聽聽After聽transferring聽the聽content聽of聽the聽container聽or聽containers聽to聽be聽tested聽
(not聽more聽than聽100聽cfu)聽to聽the聽final聽portion聽of聽sterile聽diluent聽used聽to聽rinse聽
the聽filter.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Direct聽Inoculation聽
聽聽聽聽After聽transferring聽the聽contents聽of聽the聽container聽or聽containers聽to聽be聽
tested聽(for聽catgut聽and聽other聽surgical聽sutures聽for聽veterinary聽use:聽strands)聽to聽
the聽culture聽medium,聽add聽an聽inoculum聽of聽a聽small聽number聽of聽viable聽microorganisms聽
(not聽more聽than聽100聽cfu)聽to聽the聽medium.聽
聽聽聽In聽both聽cases聽use聽the聽same聽microorganisms聽as聽those聽described聽above聽under
聽Growth聽Promotion聽Test聽of聽Aerobes,聽Anaerobes,聽and聽Fungi.聽Perform聽a聽growth聽
promotion聽test聽as聽a聽positive聽control.聽Incubate聽all聽the聽containers聽containing
聽medium聽for聽not聽more聽than聽5聽days.聽
聽聽聽If聽clearly聽visible聽growth聽of聽microorganisms聽is聽obtained聽after聽the聽
incubation,聽visually聽comparable聽to聽that聽in聽the聽control聽vessel聽without聽product,
聽either聽the聽product聽possesses聽no聽antimicrobial聽activity聽under聽the聽conditions聽
of聽the聽test聽or聽such聽activity聽has聽been聽satisfactorily聽eliminated.聽The聽test聽for聽
sterility聽may聽then聽be聽carried聽out聽without聽further聽modification.聽
聽聽聽If聽clearly聽visible聽growth聽is聽not聽obtained聽in聽the聽presence聽of聽the聽product聽to
聽be聽tested,聽visually聽comparable聽to聽that聽in聽the聽control聽vessels聽without聽
product,聽the聽product聽possesses聽antimicrobial聽activity聽that聽has聽not聽been聽
satisfactorily聽eliminated聽under聽the聽conditions聽of聽the聽test.聽Modify聽the聽
conditions聽in聽order聽to聽eliminate聽the聽antimicrobial聽activity,聽and聽repeat聽the聽
validation聽test.聽
聽聽聽This聽validation聽is聽performed聽(a)聽when聽the聽test聽for聽sterility聽has聽to聽be聽
carried聽out聽on聽a聽new聽product;聽and聽(b)聽whenever聽there聽is聽a聽change聽in聽the聽
experimental聽conditions聽of聽the聽test.聽The聽validation聽may聽be聽performed聽
simultaneously聽with聽the聽Test聽for聽Sterility聽of聽the聽Product聽to聽be聽Examined.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽TEST聽FOR聽STERILITY聽OF聽THE聽PRODUCT聽TO聽BE聽EXAMINED聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Number聽of聽Articles聽to聽Be聽Tested聽
聽聽聽聽聽Unless聽otherwise聽specified聽elsewhere聽in聽this聽chapter聽or聽in聽the聽individual
聽monograph,聽test聽the聽number聽of聽articles聽specified聽in聽Table聽3.聽If聽the聽contents聽
of聽each聽article聽are聽of聽sufficient聽quantity聽(see聽Table聽2),聽they聽may聽be聽divided聽
so聽that聽equal聽appropriate聽portions聽are聽added聽to聽each聽of聽the聽specified聽media.
聽[NOTE—Perform聽sterility聽testing聽employing聽two聽or聽more聽of聽the聽specified聽
media.]聽If聽each聽article聽does聽not聽contain聽sufficient聽quantities聽for聽each聽
medium,聽use聽twice聽the聽number聽of聽articles聽indicated聽in聽Table聽3.聽
Table聽2.聽Minimum聽Quantity聽to聽be聽Used聽for聽Each聽Medium聽
聽
聽聽聽聽聽Quantity聽per聽Container聽Minimum聽Quantity聽to聽be聽Used聽(unless聽otherwise聽
justified聽and聽authorized)聽
聽聽聽聽Liquids聽(other聽than聽anitbiotics)聽　聽
聽聽聽聽Less聽than聽1聽mL聽The聽whole聽contents聽of聽each聽container聽
聽聽聽聽1–40聽mL聽Half聽the聽contents聽of聽each聽container,聽but聽not聽less聽than聽1聽mL聽
聽聽聽聽Greater聽than聽40聽mL,聽and聽not聽greater聽than聽100聽mL聽20聽mL聽
聽聽聽聽Greater聽than聽100聽mL聽10%聽of聽the聽contents聽of聽the聽container,聽but聽not聽less聽
than聽20聽mL聽
聽聽聽聽Antibiotic聽liquids聽1聽mL聽
聽聽聽聽Other聽preparations聽soluble聽in聽water聽or聽in聽isopropyl聽myristate聽The聽whole聽
contents聽of聽each聽container聽to聽provide聽not聽less聽than聽200聽mg聽
　聽　聽
聽聽聽Insoluble聽preparations,聽creams,聽and聽ointments聽to聽be聽suspended聽or聽emulsified聽
Use聽the聽contents聽of聽each聽container聽to聽provide聽not聽less聽than聽200聽mg聽
　聽　聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Solids聽
聽聽聽Less聽than聽50聽mg：聽The聽whole聽contents聽of聽each聽container聽50聽mg聽or聽more,聽but聽
less聽than聽300聽mg聽Half聽the聽contents聽of聽each聽container,聽but聽not聽less聽than聽50聽mg聽
300聽mg–5聽g聽150聽mg聽，Greater聽than聽5聽g聽500聽mg聽
　聽　聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Devices聽　聽
聽聽聽聽聽Catgut聽and聽other聽surgical聽sutures聽for聽veterinary聽use聽3聽sections聽of聽a聽
strand聽(each聽30-cm聽long)聽
聽聽聽聽Surgical聽dressing/cotton/gauze聽(in聽packages)聽100聽mg聽per聽package聽
聽聽聽聽Sutures聽and聽other聽individually聽packaged聽single-use聽material聽The聽whole聽
device聽
聽聽聽聽Other聽medical聽devices聽The聽whole聽device,聽cut聽into聽pieces聽or聽disassembled聽

Table聽3.聽Minimum聽Number聽of聽Articles聽to聽be聽Tested聽in聽Relation聽to聽the聽Number聽of聽
Articles聽in聽the聽Batch聽
聽
Number聽of聽Items聽in聽the聽Batch聽Minimum聽Number聽of聽Items聽to聽be聽Tested聽for聽Each聽
Medium聽(unless聽otherwise聽justified聽and聽authorized)*聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Parenteral聽preparations聽　聽
聽聽Not聽more聽than聽100聽containers聽10%聽or聽4聽containers,聽whichever聽is聽the聽greater聽
聽聽More聽than聽100聽but聽not聽more聽than聽500聽containers聽10聽containers聽
聽聽More聽than聽500聽containers聽2%聽or聽20聽containers,聽whichever聽is聽less聽
聽聽For聽large-volume聽parenterals聽2%聽or聽10聽containers,聽whichever聽is聽less聽
　聽　聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Antibiotic聽solids聽　聽
聽聽Pharmacy聽bulk聽packages聽(<5聽g)聽20聽containers聽
聽聽Pharmacy聽bulk聽packages聽(鲁5聽g)聽6聽containers聽
聽聽Bulks聽and聽blends聽See聽Bulk聽solid聽products聽
　聽　聽
聽聽Ophthalmic聽and聽other聽noninjectable聽preparations聽　聽
聽聽Not聽more聽than聽200聽containers聽5%聽or聽2聽containers,聽whichever聽is聽the聽greater聽
聽聽More聽than聽200聽containers聽10聽containers聽
聽聽If聽the聽product聽is聽presented聽in聽the聽form聽of聽single-dose聽containers,聽apply聽the
聽scheme聽shown聽above聽for聽preparations聽for聽parenteral聽use.聽　聽
　聽　聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Devices聽　聽
聽聽Catgut聽and聽other聽surgical聽sutures聽for聽veterinary聽use聽2聽or5packages,whichever
聽is聽the聽greater,up聽to聽a聽maximum聽total聽of聽20聽packages聽.Not聽more聽than聽100聽
articles聽10%聽or聽4聽articles,聽whichever聽is聽greater聽.More聽than聽100,聽but聽not聽more聽
than聽500聽articles聽10聽articles聽.More聽than聽500聽articles聽2%聽or聽20聽articles,聽
whichever聽is聽less聽
　聽　聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Bulk聽solid聽products聽　聽
聽聽聽Up聽to聽4聽containers聽Each聽container聽
聽聽聽More聽than聽4聽containers,聽but聽not聽more聽than聽50聽containers聽20%聽or聽4聽
containers,聽whichever聽is聽greater聽
聽聽聽More聽than聽50聽containers聽2%聽or聽10聽containers,聽whichever聽is聽greater聽
聽聽聽If聽the聽contents聽of聽one聽container聽are聽enough聽to聽inoculate聽the聽two聽media,
聽this聽column聽gives聽the聽number聽of聽containers聽needed聽for聽both聽the聽media聽
together.聽聽
聽聽聽The聽test聽may聽be聽carried聽out聽using聽the聽technique聽of聽Membrane聽Filtration聽or聽
by聽Direct聽Inoculation聽of聽the聽Culture聽Medium聽with聽the聽product聽to聽be聽examined.
聽Appropriate聽negative聽controls聽are聽included.聽The聽technique聽of聽membrane聽
filtration聽is聽used聽whenever聽the聽nature聽of聽the聽product聽permits;聽that聽is,聽for聽
filterable聽aqueous聽preparations,聽for聽alcoholic聽or聽oily聽preparations,聽and聽for聽
preparations聽miscible聽with,聽or聽soluble聽in,聽aqueous聽or聽oily聽solvents,聽provided聽
these聽solvents聽do聽not聽have聽an聽antimicrobial聽effect聽in聽the聽conditions聽of聽the聽test.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Membrane聽Filtration聽
聽聽聽聽Use聽membrane聽filters聽having聽a聽nominal聽pore聽size聽not聽greater聽than聽0.45聽碌m
聽whose聽effectiveness聽to聽retain聽microorganisms聽has聽been聽established.聽Cellulose聽
nitrate聽filters,聽for聽example,聽are聽used聽for聽aqueous,聽oily,聽and聽weakly聽alcoholic聽
solutions;聽and聽cellulose聽acetate聽filters,聽for聽example,聽are聽used聽for聽strongly聽
alcoholic聽solutions.聽Specially聽adapted聽filters聽may聽be聽needed聽for聽certain聽
products聽(e.g.,聽for聽antibiotics).聽

聽聽聽聽The聽technique聽described聽below聽assumes聽that聽membranes聽about聽50聽mm聽in聽
diameter聽will聽be聽used.聽If聽filters聽of聽a聽different聽diameter聽are聽used,聽the聽
volumes聽of聽the聽dilutions聽and聽the聽washings聽should聽be聽adjusted聽accordingly.聽The
聽filtration聽apparatus聽and聽membrane聽are聽sterilized聽by聽appropriate聽means.聽The聽
apparatus聽is聽designed聽so聽that聽the聽solution聽to聽be聽examined聽can聽be聽introduced
聽and聽filtered聽under聽aseptic聽conditions:聽it聽permits聽the聽aseptic聽removal聽of聽the
聽membrane聽for聽transfer聽to聽the聽medium,聽or聽it聽is聽suitable聽for聽carrying聽out聽the聽
incubation聽after聽adding聽the聽medium聽to聽the聽apparatus聽itself.
聽
AQUEOUS聽SOLUTIONS聽
聽聽聽聽If聽appropriate,聽transfer聽a聽small聽quantity聽of聽a聽suitable,聽sterile聽diluent
聽such聽as聽Fluid聽A聽(see聽Diluting聽and聽Rinsing聽Fluids聽for聽Membrane聽Filtration)聽
onto聽the聽membrane聽in聽the聽apparatus聽and聽filter.聽The聽diluent聽may聽contain聽
suitable聽neutralizing聽substances聽and/or聽appropriate聽inactivating聽substances,
聽for聽example,聽in聽the聽case聽of聽antibiotics.
聽
聽聽聽Transfer聽the聽contents聽of聽the聽container聽or聽containers聽to聽be聽tested聽to聽the聽
membrane聽or聽membranes,聽if聽necessary,聽after聽diluting聽to聽the聽volume聽used聽in聽the
聽Validation聽Test聽with聽the聽chosen聽sterile聽diluent,聽but聽using聽not聽less聽than聽the
聽quantities聽of聽the聽product聽to聽be聽examined聽prescribed聽in聽Tables聽2聽and聽3.聽Filter
聽immediately.聽If聽the聽product聽has聽antimicrobial聽properties,聽wash聽the聽membrane聽
not聽less聽than聽three聽times聽by聽filtering聽through聽it聽each聽time聽the聽volume聽of聽the聽
chosen聽sterile聽diluent聽used聽in聽the聽Validation聽Test.聽Do聽not聽exceed聽a聽washing聽
cycle聽of聽5聽times聽200聽mL,聽even聽if聽during聽validation聽it聽has聽been聽demonstrated聽
that聽such聽a聽cycle聽does聽not聽fully聽eliminate聽the聽antimicrobial聽activity.聽聽聽聽聽聽聽聽聽聽
聽聽聽Transfer聽the聽whole聽membrane聽to聽the聽culture聽medium聽or聽cut聽it聽aseptically聽
into聽two聽equal聽parts,聽and聽transfer聽one聽half聽to聽each聽of聽two聽suitable聽media.聽Use聽
the聽same聽volume聽of聽each聽medium聽as聽in聽the聽Validation聽Test.聽Alternatively,聽
transfer聽the聽medium聽onto聽the聽membrane聽in聽the聽apparatus.聽Incubate聽the聽media聽for聽
not聽less聽than聽14聽days.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽SOLUBLE聽SOLIDS聽(other聽than聽antibiotics)聽
聽聽聽Use聽for聽each聽medium聽not聽less聽than聽the聽quantity聽prescribed聽in聽Tables聽2聽and聽3聽
of聽the聽product聽dissolved聽in聽a聽suitable聽solvent,聽such聽as聽Fluid聽A聽(Diluting聽and聽
Rinsing聽Fluids聽for聽Membrane聽Filtration),聽and聽proceed聽with聽the聽test聽as聽
described聽above聽for聽Aqueous聽Solutions聽using聽a聽membrane聽appropriate聽to聽the聽
chosen聽solvent.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽OILS聽AND聽OILY聽SOLUTIONS聽
聽聽聽Use聽for聽each聽medium聽not聽less聽than聽the聽quantity聽of聽the聽product聽prescribed聽in聽
Tables聽2聽and聽3.聽Oils聽and聽oily聽solutions聽of聽sufficiently聽low聽viscosity聽may聽be聽
filtered聽without聽dilution聽through聽a聽dry聽membrane.聽Viscous聽oils聽may聽be聽diluted聽
as聽necessary聽with聽a聽suitable聽sterile聽diluent聽such聽as聽isopropyl聽myristate聽shown
聽not聽to聽have聽antimicrobial聽activity聽in聽the聽conditions聽of聽the聽test.聽Allow聽the聽
oil聽to聽penetrate聽the聽membrane聽by聽its聽own聽weight,聽and聽then聽filter,聽applying聽the
聽pressure聽or聽suction聽gradually.聽Wash聽the聽membrane聽at聽least聽three聽times聽by聽
filtering聽through聽it聽each聽time聽about聽100聽mL聽of聽a聽suitable聽sterile聽solution聽
such聽as聽Fluid聽A聽(see聽Diluting聽and聽Rinsing聽Fluids聽for聽Membrane聽Filtration)聽
containing聽a聽suitable聽emulsifying聽agent聽at聽a聽concentration聽shown聽to聽be聽
appropriate聽in聽the聽validation聽of聽the聽test,聽for聽example聽polysorbate聽80聽at聽a聽
concentration聽of聽10聽g聽per聽L聽(Fluid聽K).聽Transfer聽the聽membrane聽or聽membranes聽to聽
the聽culture聽medium聽or聽media,聽or聽vice聽versa,聽as聽described聽above聽for聽Aqueous聽
Solutions,聽and聽incubate聽at聽the聽same聽temperatures聽and聽for聽the聽same聽times.聽

聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽OINTMENTS聽AND聽CREAMS聽
聽聽聽Use聽for聽each聽medium聽not聽less聽than聽the聽quantities聽of聽the聽product聽prescribed聽
in聽Tables聽2聽and聽3.聽Ointments聽in聽a聽fatty聽base聽and聽emulsions聽of聽the聽water-in-oil
聽type聽may聽be聽diluted聽to聽1%聽in聽isopropyl聽myristate聽as聽described聽above,聽by聽
heating,聽if聽necessary,聽to聽not聽more聽than聽40.聽In聽exceptional聽cases聽it聽may聽be聽
necessary聽to聽heat聽to聽not聽more聽than聽44.聽Filter聽as聽rapidly聽as聽possible,聽and聽
proceed聽as聽described聽above聽for聽Oils聽and聽Oily聽Solutions.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽PREFILLED聽SYRINGES聽
聽聽For聽prefilled聽syringes聽without聽attached聽sterile聽needles,聽expel聽the聽contents聽
of聽each聽syringe聽into聽one聽or聽two聽separate聽membrane聽filter聽funnels聽or聽into聽
separate聽pooling聽vessels聽prior聽to聽transfer.聽If聽a聽separate聽sterile聽needle聽is聽
attached,聽directly聽expel聽the聽syringe聽contents聽as聽indicated聽above,聽and聽proceed聽
as聽directed聽for聽Aqueous聽Solutions.聽Test聽the聽sterility聽of聽the聽needle,聽using聽
Direct聽Inoculation聽under聽Validation聽Test.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽SOLIDS聽FOR聽INJECTION聽OTHER聽THAN聽ANTIBIOTICS聽
聽聽聽Constitute聽the聽test聽articles聽as聽directed聽on聽the聽label,聽and聽proceed聽as聽
directed聽for聽Aqueous聽Solutions聽or聽Oils聽and聽Oily聽Solutions,聽whichever聽applies.
聽[NOTE—If聽necessary,聽excess聽diluent聽can聽be聽added聽to聽aid聽in聽the聽constitution聽
and聽filtration聽of聽the聽constituted聽test聽article.]聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽ANTIBIOTIC聽SOLIDS聽FOR聽INJECTION聽
聽聽聽Pharmacy聽Bulk聽Packages,聽<聽5聽g—聽From聽each聽of聽20聽containers,聽aseptically聽
transfer聽about聽300聽mg聽of聽solids,聽into聽a聽sterile聽500-mL聽conical聽flask,聽dissolve聽
in聽about聽200聽mL聽of聽Fluid聽A聽(see聽Diluting聽and聽Rinsing聽Fluids聽for聽Membrane聽
Filtration),聽and聽mix;聽or聽constitute,聽as聽directed聽in聽the聽labeling,聽each聽of聽20聽
containers聽and聽transfer聽a聽quantity聽of聽liquid聽or聽suspension,聽equivalent聽to聽
about聽300聽mg聽of聽solids,聽into聽a聽sterile聽500-mL聽conical聽flask,聽dissolve聽in聽about
聽200聽mL聽of聽Fluid聽A,聽and聽mix.聽Proceed聽as聽directed聽for聽Aqueous聽Solutions聽or聽Oils
聽and聽Oily聽Solutions,聽whichever聽applies.聽
聽聽聽Pharmacy聽Bulk聽Packages,聽鲁5聽g—聽From聽each聽of聽6聽containers,聽aseptically聽
transfer聽about聽1聽g聽of聽solids聽into聽a聽sterile聽500-mL聽conical聽flask,聽dissolve聽in聽
about聽200聽mL聽of聽Fluid聽A,聽and聽mix;聽or聽constitute,聽as聽directed聽in聽the聽labeling,
聽each聽of聽6聽containers聽and聽transfer聽a聽quantity聽of聽liquid,聽equivalent聽to聽about聽1
聽g聽of聽solids,聽into聽a聽sterile聽500-mL聽conical聽flask,聽dissolve聽in聽about聽200聽mL聽of
聽Fluid聽A,聽and聽mix.聽Proceed聽as聽directed聽for聽Aqueous聽Solutions.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽ANTIBIOTIC聽SOLIDS,聽BULKS,聽AND聽BLENDS聽
聽聽聽Aseptically聽remove聽a聽sufficient聽quantity聽of聽solids聽from聽the聽appropriate聽
amount聽of聽containers聽(see聽Table聽2),聽mix聽to聽obtain聽a聽composite,聽equivalent聽to聽
about聽6聽g聽of聽solids,聽and聽transfer聽to聽a聽sterile聽500-mL聽conical聽flask.聽Dissolve聽
in聽about聽200聽mL聽of聽Fluid聽A,聽and聽mix.聽Proceed聽as聽directed聽for聽Aqueous聽Solutions.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽STERILE聽AEROSOL聽PRODUCTS聽
聽聽聽For聽fluid聽products聽in聽pressurized聽aerosol聽form,聽freeze聽the聽containers聽in聽an聽
alcohol-dry聽ice聽mixture聽at聽least聽at聽–20聽for聽about聽1聽hour.聽If聽feasible,聽allow聽
the聽propellant聽to聽escape聽before聽aseptically聽opening聽the聽container,聽and聽
transfer聽the聽contents聽to聽a聽sterile聽pooling聽vessel.聽Add聽100聽mL聽of聽Fluid聽D聽to聽
the聽pooling聽vessel,聽and聽mix聽gently.聽Proceed聽as聽directed聽for聽Aqueous聽Solutions
聽or聽Oils聽and聽Oily聽Solutions,聽whichever聽applies.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽DEVICES聽WITH聽PATHWAYS聽LABELED聽STERILE聽
聽聽聽Aseptically聽pass聽not聽less聽than聽10聽pathway聽volumes聽of聽Fluid聽D聽through聽each
聽device聽tested.聽Collect聽the聽fluids聽in聽an聽appropriate聽sterile聽vessel,聽and
聽proceed聽as聽directed聽for聽Aqueous聽Solutions聽or聽Oils聽and聽Oily聽Solutions,聽
whichever聽applies.聽
聽聽聽In聽the聽case聽of聽sterile,聽empty聽syringes,聽draw聽sterile聽diluent聽into聽the聽
barrel聽through聽the聽sterile聽needle,聽if聽attached,聽or聽through聽a聽sterile聽needle聽
attached聽for聽the聽purpose聽of聽the聽test,聽and聽express聽the聽contents聽into聽a聽sterile聽
pooling聽vessel.聽Proceed聽as聽directed聽above.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽Direct聽Inoculation聽of聽the聽Culture聽Medium聽
聽聽聽Transfer聽the聽quantity聽of聽the聽preparation聽to聽be聽examined聽prescribed聽in聽
Tables聽2聽and聽3聽directly聽into聽the聽culture聽medium聽so聽that聽the聽volume聽of聽the聽
product聽is聽not聽more聽than聽10%聽of聽the聽volume聽of聽the聽medium,聽unless聽otherwise聽
prescribed.聽
聽聽聽If聽the聽product聽to聽be聽examined聽has聽antimicrobial聽activity,聽carry聽out聽the聽
test聽after聽neutralizing聽this聽with聽a聽suitable聽neutralizing聽substance聽or聽by聽
dilution聽in聽a聽sufficient聽quantity聽of聽culture聽medium.聽When聽it聽is聽necessary聽to聽
use聽a聽large聽volume聽of聽the聽product,聽it聽may聽be聽preferable聽to聽use聽a聽concentrated聽
culture聽medium聽prepared聽in聽such聽a聽way聽that聽it聽takes聽into聽account聽the聽
subsequent聽dilution.聽Where聽appropriate,聽the聽concentrated聽medium聽may聽be聽added聽
directly聽to聽the聽product聽in聽its聽container.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽OILY聽LIQUIDS聽
聽聽聽聽Use聽media聽to聽which聽have聽been聽added聽a聽suitable聽emulsifying聽agent聽at聽a聽
concentration聽shown聽to聽be聽appropriate聽in聽the聽validation聽of聽the聽test,聽for聽
example聽polysorbate聽80聽at聽a聽concentration聽of聽10聽g聽per聽liter.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽OINTMENTS聽AND聽CREAMS聽
聽聽聽聽Prepare聽by聽diluting聽to聽about聽1聽in聽10聽by聽emulsifying聽with聽the聽chosen聽
emulsifying聽agent聽in聽a聽suitable聽sterile聽diluent聽such聽as聽Fluid聽A聽(see聽Diluting聽
and聽Rinsing聽Fluids聽for聽Membrane聽Filtration).聽Transfer聽the聽diluted聽product聽to聽a聽
medium聽not聽containing聽an聽emulsifying聽agent.聽
聽聽聽Incubate聽the聽inoculated聽media聽for聽not聽less聽than聽14聽days.聽Observe聽the聽
cultures聽several聽times聽during聽the聽incubation聽period.聽Shake聽cultures聽containing聽
oily聽products聽gently聽each聽day.聽However,聽when聽thioglycollate聽medium聽or聽other
聽similar聽medium聽is聽used聽for聽the聽detection聽of聽anaerobic聽microorganisms,聽keep聽
shaking聽or聽mixing聽to聽a聽minimum聽in聽order聽to聽maintain聽anaerobic聽conditions.聽
聽聽聽聽聽聽聽聽聽CATGUT聽AND聽OTHER聽SURGICAL聽SUTURES聽FOR聽VETERINARIAN聽USE聽
Use聽for聽each聽medium聽not聽less聽than聽the聽quantities聽of聽the聽product聽prescribed聽in
聽Tables聽2聽and聽3.聽Open聽the聽sealed聽package聽using聽aseptic聽precautions,聽and聽remove
聽three聽sections聽of聽the聽strand聽for聽each聽culture聽medium.聽Carry聽out聽the聽test聽on聽
three聽sections,聽each聽30-cm聽long,聽which聽have聽been聽cut聽off聽from聽the聽beginning,聽
the聽center,聽and聽the聽end聽of聽the聽strand.聽Use聽whole聽strands聽from聽freshly聽opened聽
cassette聽packs.聽Transfer聽each聽section聽of聽the聽strand聽to聽the聽selected聽medium.
聽Use聽sufficient聽medium聽to聽cover聽adequately聽the聽material聽to聽be聽tested聽(20聽mL聽to聽150聽mL).聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽SOLIDS聽
聽聽聽聽Transfer聽a聽quantity聽of聽the聽product聽in聽the聽form聽of聽a聽dry聽solid聽(or聽prepare聽
a聽suspension聽of聽the聽product聽by聽adding聽sterile聽diluent聽to聽the聽immediate聽
container),聽corresponding聽to聽not聽less聽than聽the聽quantity聽indicated聽in聽Tables聽2聽
and聽3.聽Transfer聽the聽material聽so聽obtained聽to聽200聽mL聽of聽Fluid聽Thioglycollate聽
Medium,聽and聽mix.聽Similarly,聽transfer聽the聽same聽quantity聽to聽200聽mL聽of聽Soybean–
Casein聽Digest聽Medium,聽and聽mix.聽Proceed聽as聽directed聽above.聽
聽聽聽聽聽聽PURIFIED聽COTTON,聽GAUZE,聽SURGICAL聽DRESSINGS,聽AND聽RELATED聽ARTICLES聽
聽聽From聽each聽package聽of聽cotton,聽rolled聽gauze聽bandage,聽or聽large聽surgical聽
dressings聽being聽tested,聽aseptically聽remove聽two聽or聽more聽portions聽of聽100-聽to聽500-
mg聽each聽from聽the聽innermost聽part聽of聽the聽sample.聽From聽individually聽packaged,聽
single-use聽materials,聽aseptically聽remove聽the聽entire聽article.聽Immerse聽the
聽portions聽or聽article聽in聽each聽medium,聽and聽proceed聽as聽directed聽above.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽STERILE聽DEVICES聽
聽聽聽Articles聽can聽be聽immersed聽intact聽or聽disassembled.聽To聽ensure聽that聽device聽
pathways聽are聽also聽in聽contact聽with聽the聽media,聽immerse聽the聽appropriate聽number聽of
聽units聽per聽medium聽in聽a聽volume聽of聽medium聽sufficient聽to聽immerse聽the聽device聽
completely,聽and聽proceed聽as聽directed聽above.聽For聽extremely聽large聽devices,聽
immerse聽those聽portions聽of聽the聽device聽that聽are聽to聽come聽into聽contact聽with聽the聽
patient聽in聽a聽volume聽of聽medium聽sufficient聽to聽achieve聽complete聽immersion聽of聽
those聽portions.聽
聽聽For聽catheters聽where聽the聽inside聽lumen聽and聽outside聽are聽required聽to聽be聽sterile,聽
either聽cut聽them聽into聽pieces聽such聽that聽the聽medium聽is聽in聽contact聽with聽the聽entire聽
lumen聽or聽fill聽the聽lumen聽with聽medium,聽and聽then聽immerse聽the聽intact聽unit.聽
聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽聽OBSERVATION聽AND聽INTERPRETATION聽OF聽RESULTS聽
聽聽聽At聽intervals聽during聽the聽incubation聽period聽and聽at聽its聽conclusion,聽examine聽
the聽media聽for聽macroscopic聽evidence聽of聽microbial聽growth.聽If聽the聽material聽being
聽tested聽renders聽the聽medium聽turbid聽so聽that聽the聽presence聽or聽absence聽of聽microbial
聽growth聽cannot聽be聽readily聽determined聽by聽visual聽examination,聽14聽days聽after聽the
聽beginning聽of聽incubation聽transfer聽portions聽(each聽not聽less聽than聽1聽mL)聽of聽the聽
medium聽to聽fresh聽vessels聽of聽the聽same聽medium,聽and聽then聽incubate聽the聽original聽and聽
transfer聽vessels聽for聽not聽less聽than聽4聽days.聽
聽聽聽If聽no聽evidence聽of聽microbial聽growth聽is聽found,聽the聽product聽to聽be聽examined聽
complies聽with聽the聽test聽for聽sterility.聽If聽evidence聽of聽microbial聽growth聽is聽
found,聽the聽product聽to聽be聽examined聽does聽not聽comply聽with聽the聽test聽for聽sterility,
聽unless聽it聽can聽be聽clearly聽demonstrated聽that聽the聽test聽was聽invalid聽for聽causes聽
unrelated聽to聽the聽product聽to聽be聽examined.聽The聽test聽may聽be聽considered聽invalid聽
only聽if聽one聽or聽more聽of聽the聽following聽conditions聽are聽fulfilled:聽

The聽data聽of聽the聽microbiological聽monitoring聽of聽the聽sterility聽testing聽facility聽
show聽a聽fault.聽
聽聽聽A聽review聽of聽the聽testing聽procedure聽used聽during聽the聽test聽in聽question聽reveals聽
a聽fault.聽
聽聽聽Microbial聽growth聽is聽found聽in聽the聽negative聽controls.聽
聽聽聽After聽determination聽of聽the聽identity聽of聽the聽microorganisms聽isolated聽from聽the聽
test,聽the聽growth聽of聽this聽species聽(or聽these聽species)聽may聽be聽ascribed聽
unequivocally聽to聽faults聽with聽respect聽to聽the聽material聽and聽or聽the聽technique聽used聽
in聽conducting聽the聽sterility聽test聽procedure.聽
聽聽聽If聽the聽test聽is聽declared聽to聽be聽invalid,聽it聽is聽repeated聽with聽the聽same聽number
聽of聽units聽as聽in聽the聽original聽test.聽If聽no聽evidence聽of聽microbial聽growth聽is聽found聽
in聽the聽repeat聽test,聽the聽product聽examined聽complies聽with聽the聽test聽for聽sterility.
聽If聽microbial聽growth聽is聽found聽in聽the聽repeat聽test,聽the聽product聽examined聽does聽
not聽comply聽with聽the聽test聽for聽sterility.聽
聽聽APPLICATION聽OF聽THE聽TEST聽TO聽PARENTERAL聽PREPARATIONS,聽OPHTHALMIC,聽AND聽OTHER聽
NONINJECTABLE聽PREPARATIONS聽REQUIRED聽TO聽COMPLY聽WITH聽THE聽TEST聽FOR聽STERILITY聽
聽聽聽When聽using聽the聽technique聽of聽membrane聽filtration,聽use,聽whenever聽possible,
聽the聽whole聽contents聽of聽the聽container,聽but聽not聽less聽than聽the聽quantities聽
indicated聽in聽Tables聽2聽and聽3,聽diluting聽where聽necessary聽to聽about聽100聽mL聽with聽a聽
suitable聽sterile聽solution,聽such聽as聽Fluid聽A聽(see聽Diluting聽and聽Rinsing聽Fluids聽
for聽Membrane聽Filtration).聽
聽聽聽When聽using聽the聽technique聽of聽direct聽inoculation聽of聽media,聽use聽the聽quantities
聽shown聽in聽Tables聽2聽and聽3,聽unless聽otherwise聽justified聽and聽authorized.聽The聽tests聽
for聽bacterial聽and聽fungal聽sterility聽are聽carried聽out聽on聽the聽same聽sample聽of聽the聽
product聽to聽be聽examined.聽When聽the聽volume聽or聽the聽quantity聽in聽a聽single聽container聽
is聽insufficient聽to聽carry聽out聽the聽tests,聽the聽contents聽of聽two聽or聽more聽containers聽
are聽used聽to聽inoculate聽the聽different聽media.
聽聽聽In聽appropriate聽cases,聽periodic聽testing聽of聽the聽different聽batches聽prepared聽
from聽the聽same聽lot聽of聽dehydrated聽medium聽is聽acceptable.聽
聽聽聽
聽聽聽

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