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Flashcards in Formulation Deck (53)
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1

ICH Q5 is guidelines for what

quality of biotechnological products

2

Q5A

viral safety evaluation of products derived from cell lines

3

Q5B

analysis of the expression construct in cells used for production of rDNA derived protein products

4

Q5C

stability

5

Q5D

derivation and characterization of cell substrates used for production

6

ICH Q6B specifications for

test procedures and acceptance criteria
includes in process controls, bulk drug, final product and stability specifications

7

how are biotechnological products sterilized

filtration
prefiltration remove bioburden and other particulates
sterilize by filtering through 0.2um membrane filters

8

3Es you need to sterilze

equipment
excipients
environment

9

ways to sterilize the facilities

dry heat autoclave >160C for 30min
chemical treatment
gamma radiation

10

1 endotoxin unit =

100pg of ecoli LPS
amount in 10^5 bacteria

11

____ EU/kg body weight can cause _____ symptoms

5
fever, low BP, increased Hr, decreased urine output

12

explain pyrogen induced fever

viruses and bacteria stimulate phagocytic cells which release prostaglandin E2
activates the hypothalamus to increase the temperature set point

13

max EU units for the following
1. intrathecal injection
2. non intrathecal injection
3. sterile water

1. 0.2 EU/kg body weight
2. 0.5
3. 0.25-0.5 EU/mL

14

pyrogens can be detecting using rabbits becuase they have a similar endotoxin tolerance but whats the problem with this

cant quantify

15

what is the limulis amebocyte lyase test

horse shoe crab blood forms clots when exposed to endotoxin
take amebocyte extract from the blood and mix with samples to test to determine pyrogen levels

16

benefits of LAL pyrogen test

fast <30 min
highly sensitive - up to 0.005EU

17

how can pyrogens be removed

charcoal - offers hydrophobic interactions
ion exchange chromatography

18

explain how ion exchange chromatography works

cations line the column
negatively charged endotoxins stick to the sides and proteins are expelled

19

4 ways to remove pyrogens from equipment

oxidation - hydrogen peroxide
heat - 250 for 30 min
acid base hydrolysis - cleave lipid A from polysacharide
sodium hydroxide - clean ion exhange

20

examples of physical instability

adsorption
precipitate formation
denaturation
aggregation

21

excipients used to prevent physical instability

osmotic agents
buffer components
solubility enhancers
antiaggregate and antoadsorbant

22

formation of aggregation can be due to

electrostatic or hydrophobic interactions
formation of covalent bridge with disulfide bonds or ester linkages

23

addition of lysine or arginine solubilizes

tPa

24

addition of sodium dodecylsulfate surfactant solubilizes

non glycosylated IL2

25

anti adsorptive agents reduce

adsorption of active proteins to interfaces ex. water, container, administrative utensils

26

example of irreversible aggregation

hydrophobic parts of aqeuous phase adsorb to hydrophobic interface

27

what do surfactants do

adsorb to hydrophobic interface with their own hydrophobic groups to make the surface hydrophilic to the aqeuous phase

28

example of antiadsorbant in insulin

albumin

29

how do you prevent fibrillar precipitates formation

low concentrations of phospholipids and surfactants
proper pH

30

what iis the most important part of the formation process

adjusting pH with buffer