8 Flashcards
sterility assurance level
1 in 10 power 6 probability of a viable microorganism (non sterility)
sterility is required for
preps for irrigation, opthalmic preps and parenteral preps
bioburden in manufacturing steps must be
minimised before sterilisation
what are examples of pyrogens
endotoxins which are lipopolysaccharides produced by g neg bacteria eg e coli
inactivation factor
degree to which biological indicator is reduced by sterilising treatment
overkill approach
12 log reduction in the biological indicator (microorganism) through the sterilising process
SAL
indicates the probability of one viable microorganism in certain no of drug products usually 10 power 6
suitability test
validity of sterility test: spike test with known quantities of microorganisms. incubate for 3-5 days and compare turbidity. if test sample has same tubidity as positive control –> not sterile
2 types of sterility tests
membrane filtration and direct inoculation.
main source of contamination
people. use a isolator
growth promotion test
validation of sterility test. used to confirm that rage culture media can support the growth of less than 10 viable microorganisms if it cannot, it fails. A portion also tested for sterility and if not sterile the test fails
endotoxin test
LAL limulus amoebacyte lysate test. clotting of blood indicated presence of endotoxins
endotoxins lead to release of
cytokines and interleukins
endotoxin limit conc formula
elc= K/M
M Is max recommended dose (kg/h)
K is max endotoxins dose usually 5
max valid dilution
mvd = ELC/ method sensitivity
use lowest dilution you can get
sterile biologic drugs are manufactured by sterile filtration followed by
aseptic filling and processing
how to reduce bio burden
use aseptic handling techniques everywhere possible
reduce microbial load prior to and on sterile filter with pre filters
increase effective filter surface area by using larger single filter or multiple filters in series
limit batch vol to be sterile filtered
test integrity of sterilising filters pre and post use
D value
time required for sterilisation process to achieve a 90% reduction in microbial population (one log reduction)
issues with sub visible/ visible particles
adverse rections eg mechanical obstruction with lung as a target
injection site reactions eg phlebitis
test for sub visible particles
light obscuration particle count test
microscopic particle count test
requirement for light obscuration .. test
(only for sub visible particles) should not exceed 6000 per container more than 10 micrometers and 600 greater than 25 micrometers
microscopic particle test should be
free of visible particles
same as light obscuration test for sub visible particles
6 types of sterilisation methods
dry heat, moist heat, lyophilisation, aseptic filtration, nitrous/ethylene oxide/h2o2 fog, gamma radiation
aseptic process simulation
validating an aseptic process to simulate the process the product itself will undergo
aseptic filtration filter size
0.22 micrometers
aseptic filtration description
what is not removed
sterile filtrate is produced.
pyrogens and bacteria and mould are removed but viruses and mycoplasma not removed so heat treatments needed.
lyophilisation aka __
describe process
freeze drying.
water is removed from a product after it is frozen and placed in vacuum, allowing the ice to change from solid to vapour directly
7 steps of lyophilisation process
- dissolve drug and excipients in suitable solvent, usually water for injection
- sterilise bulk solution by passing though a 0.22 micron BACTERIA RETENTIVE filter
- filling into individual sterile containers and partially stoppering the containers under aseptic conditions
- transporting the containers to lyophiliser and loading under aseptic conditions
- freezing solution by placing partially stoppered containers on cooled shelves in free drying chamber
- applying vacuum to chamber er and heating shelves to evaporate water
- complete stoppering of vials by hydraulic or screw rod mechanisms installed in lyophilisers
3 processes in lyophilisation
freezing, primary drying (sublimation), secondary drying (description to remove most water)
which medium to use for aseptic process simulation for powder
for aerobic bacteria, fungi and yeast - soybean casein digest medium
for aerobic bacteria = fluid thioglicollate medium
for yeast - sabouraud dextrose agar
when is a sterile powder needed
when drug is unstable in liquid form
sterile powder must be reconstituted with____ before administration
sterile diluent
6 components of injections
vehicle, antimicrobial agent, tonicity adjuster, dispersing agent and surfactant, buffer, antioxidant
7 examples of dispersing agents (prevent agglomeration and promote solubilisation)
lecithin
carboxymethylcellulose
methyl cellulose
acacia
gelatin
Tween 80
Pluronic F68
preservatives for injections - 9
thimerosal
parabens
BAK
phenyl mercuric nitrate
phenol
chlorocresol
benzethonium chloride
benzyl alcohol
chlorbutanol
small vol IV bags - piggy backs vs continuous preps
small vol is administered over short time at specific intervals (less than 250ml)
continuous preps are either large vol or drips
what sterilisation is necessary for IV bags
terminal
what do multi dose vials usually contain
preservatives
can retain sterility after puncture
are epidurals preservative free?
yes as they can cause paralysis
what does irrigation usually contain
must be sterile, usually w gentamicin
how long does albumin last once opened
4h
plasma protein fraction dosing
single dose IV administration
immunoglobulin notes
must be sterile and lyophilised
must be recostitued before administration
how are opthlamics manufactured
aseptic filtration technique
which is performed first suitability test or growth promotion test
growth promotion test to see if medium can support the selected strain and no other strains. then do suitability test and check for sample sterility
