8

Question 1

sterility assurance level

Answer 1

1 in 10 power 6 probability of a viable microorganism (non sterility)

Question 2

sterility is required for

Answer 2

preps for irrigation, opthalmic preps and parenteral preps

Question 3

bioburden in manufacturing steps must be

Answer 3

minimised before sterilisation

Question 4

what are examples of pyrogens

Answer 4

endotoxins which are lipopolysaccharides produced by g neg bacteria eg e coli

Question 5

inactivation factor

Answer 5

degree to which biological indicator is reduced by sterilising treatment

Question 6

overkill approach

Answer 6

12 log reduction in the biological indicator (microorganism) through the sterilising process

Question 7

SAL

Answer 7

indicates the probability of one viable microorganism in certain no of drug products usually 10 power 6

Question 8

suitability test

Answer 8

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

Question 9

2 types of sterility tests

Answer 9

membrane filtration and direct inoculation.

Question 10

main source of contamination

Answer 10

people. use a isolator

Question 11

growth promotion test

Answer 11

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

Question 12

endotoxin test

Answer 12

LAL limulus amoebacyte lysate test. clotting of blood indicated presence of endotoxins

Question 13

endotoxins lead to release of

Answer 13

cytokines and interleukins

Question 14

endotoxin limit conc formula

Answer 14

elc= K/M
M Is max recommended dose (kg/h)
K is max endotoxins dose usually 5

Question 15

max valid dilution

Answer 15

mvd = ELC/ method sensitivity
use lowest dilution you can get

Question 16

sterile biologic drugs are manufactured by sterile filtration followed by

Answer 16

aseptic filling and processing

Question 17

how to reduce bio burden

Answer 17

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

Question 18

D value

Answer 18

time required for sterilisation process to achieve a 90% reduction in microbial population (one log reduction)

Question 19

issues with sub visible/ visible particles

Answer 19

adverse rections eg mechanical obstruction with lung as a target
injection site reactions eg phlebitis

Question 20

test for sub visible particles

Answer 20

light obscuration particle count test
microscopic particle count test

Question 21

requirement for light obscuration .. test

Answer 21

(only for sub visible particles) should not exceed 6000 per container more than 10 micrometers and 600 greater than 25 micrometers

Question 22

microscopic particle test should be

Answer 22

free of visible particles
same as light obscuration test for sub visible particles

Question 23

6 types of sterilisation methods

Answer 23

dry heat, moist heat, lyophilisation, aseptic filtration, nitrous/ethylene oxide/h2o2 fog, gamma radiation

Question 24

aseptic process simulation

Answer 24

validating an aseptic process to simulate the process the product itself will undergo

Question 25

aseptic filtration filter size

Answer 25

0.22 micrometers

Question 26

aseptic filtration description what is not removed

Answer 26

sterile filtrate is produced. pyrogens and bacteria and mould are removed but viruses and mycoplasma not removed so heat treatments needed.

Question 27

lyophilisation aka __ describe process

Answer 27

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

Question 28

7 steps of lyophilisation process

Answer 28

- 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

Question 29

3 processes in lyophilisation

Answer 29

freezing, primary drying (sublimation), secondary drying (description to remove most water)

Question 30

which medium to use for aseptic process simulation for powder

Answer 30

for aerobic bacteria, fungi and yeast - soybean casein digest medium for aerobic bacteria = fluid thioglicollate medium for yeast - sabouraud dextrose agar

Question 31

when is a sterile powder needed

Answer 31

when drug is unstable in liquid form

Question 32

sterile powder must be reconstituted with____ before administration

Answer 32

sterile diluent

Question 33

6 components of injections

Answer 33

vehicle, antimicrobial agent, tonicity adjuster, dispersing agent and surfactant, buffer, antioxidant

Question 34

7 examples of dispersing agents (prevent agglomeration and promote solubilisation)

Answer 34

lecithin carboxymethylcellulose methyl cellulose acacia gelatin Tween 80 Pluronic F68

Question 35

preservatives for injections - 9

Answer 35

thimerosal parabens BAK phenyl mercuric nitrate phenol chlorocresol benzethonium chloride benzyl alcohol chlorbutanol

Question 36

small vol IV bags - piggy backs vs continuous preps

Answer 36

small vol is administered over short time at specific intervals (less than 250ml) continuous preps are either large vol or drips

Question 37

what sterilisation is necessary for IV bags

Answer 37

terminal

Question 38

what do multi dose vials usually contain

Answer 38

preservatives can retain sterility after puncture

Question 39

are epidurals preservative free?

Answer 39

yes as they can cause paralysis

Question 40

what does irrigation usually contain

Answer 40

must be sterile, usually w gentamicin

Question 41

how long does albumin last once opened

Answer 41

4h

Question 42

plasma protein fraction dosing

Answer 42

single dose IV administration

Question 43

immunoglobulin notes

Answer 43

must be sterile and lyophilised must be recostitued before administration

Question 44

how are opthlamics manufactured

Answer 44

aseptic filtration technique

Question 45

which is performed first suitability test or growth promotion test

Answer 45

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