Stability of biologies

Question 1

What are biologies?

Answer 1

thoes are pharmaceutical products obtained diretly from living organism.

Question 2

Examples of biologicals

Answer 2

Blood plasma products, vaccines

antivenoms

Question 3

Why are biologies stored at low temperature?

Answer 3

Because there are more labile

Question 4

is there any difference regarding the climatic zones?

Answer 4

For cold or frozen product there is no different

Question 5

where does the activity of biologies comes from

Answer 5

from protein

Question 6

structures of protein

Answer 6

covalently bounded primary structure

folder conformation: secondary and tertiary structure

Question 7

What happend when there is a change in the conformation?

Answer 7

the protein will be in the denatured state, resultsing to loss of biological activity

Question 8

Common bioassay

Answer 8

ELISA and immunblot methods

Question 9

Method for the distribution of proteins

Answer 9

size-exclusion HPLC, SDS-Page

Question 10

How can protein instabilities be categorized

Answer 10

Aggregation, deamidation, denaturation and oxidation

Question 11

How can the proteine instability be divided

Answer 11

Chemical and pysical instabilities

Question 12

What are chemical instabilities?

Answer 12

break or cvalent bonds, resulting in new chemical enthities

Question 13

it is possibe to clearly discern the different instability (chemical and physical)

Answer 13

no, not always possible

Question 14

Which amino acids preperably undergo oxidation and deamidation reactions?

Answer 14

Cysteine, histidine and tyrosine for oxidation

Glutamate

Question 15

What does deamidation means?

Answer 15

Removal of the amino acid and converted to ammonia, which whoes toxic activity

Question 16

What does physical instability means?

Answer 16

Changes its pyhsical state without any change in the chemical composition

Question 17

Example of pyhsical change

Answer 17

Aggregation and precipitation and denaturation

Question 18

How is the conformational stabiliy achieved?

Answer 18

optimization of the structural stability of the protein by maximinzing the gibbs energy

Question 19

How can the gibbs energies be measured?

Answer 19

Differential scanning calorimetry (DSC) and isothermal chemical denaturation (ICD)

Question 20

What causes aggregation in protein ?

Answer 20

incorrect folding druing protein expression.

Question 21

what is the most influential factor in modulating aggregation?

Answer 21

the conformational stability

Question 22

How are biologics administered?

Answer 22

parenterally

Question 23

What are the requirements for parenteral products?

Answer 23

Sterile, free from visable particles,

Question 24

How can the conformation stabilization achieved in aquaous solution?

Answer 24

By applying sugar or polyol ,this are osmoytes which increases the conformational stability to proteins
Also salts

Question 25

Which sugars should be avoided here? | What know reaction can occur

Answer 25

Sugras with protines reactions (lactse, reduced surgers). there will covalently bond to the sugar and so lose of the effcient

Question 26

How can proteins be conformational stabilization?

Answer 26

by ligand inding to the native state by ions by drying

Question 27

Stabilization by drying?

Answer 27

lyophilization

Question 28

Stabilization of proteins by ions?

Answer 28

adding of salts to protein solution, specific interactions (binding of cations or anions directly to the protein

Question 29

Stabilization of proteins by ligand binding

Answer 29

ligands which bind selectively to the naive state resulsting in net stabilization. excipients (including surfactants

Question 30

what could happend during freezing?

Answer 30

cold denaturation could occure, prevention by adding non-ionic surfactants (polysorbate 20 or 80)

Question 31

improvement of protein stability during freezedrying

Answer 31

plasticizers (water, glycerol or sorbitol) | buclking agents such as mannitol or glycine

Question 32

what are the relevant ICH guidlines?

Answer 32

ICH Q1 A(R2) for general requirements ICH Q5C guideline for additional consideration ICH Q6B specification for boilogics ICH Q5E for biotechological/biological products

Question 33

does the guidlines QC5 cover antibiotics, heparins or vitamine

Answer 33

No

Question 34

for what can the ICH Q1 staibility guidlines used for?

Answer 34

generally applicable to biologics, good starting place for designing stabiity protocols

Question 35

For how many batches should stability date be provided (drug substance)

Answer 35

at least three batches, representative of the manufacturing scale of production

Question 36

stability study of the drug product

Answer 36

at least three batches of final container prouct

Question 37

What is a stability-indicating profile?

Answer 37

it should assure that change in identity, purity and potency of the product will be detected

Question 38

Purity and molecular characterization method?

Answer 38

SDS-page, western blots

Question 39

what are other product characteristics?

Answer 39

Viscual appearance, sterility tessting, additivies and container/closure

Question 40

What is a biosimilar?

Answer 40

is a biological medicine highly similar to another already approved biological medicine interms of structure, biological activity and efficacy, saftey and immuogenicity profile

Question 41

What is necessary for the demonstration of bioequivalence

Answer 41

that will be for generic products, pharmacological studies

Question 42

Why are BE-study not suitbale for biosimilar?

Answer 42

Because of their different pharmacokinetics and stability of the biosilmilar

Question 43

What studies have to be conducted for biosimilar?

Answer 43

clinical studies, to check the efficacy, phase 3 studies

Question 44

According to which criteria is the reference product selected?

Answer 44

nterms of structure, biological activity and efficacy, saftey and immuogenicity profile

Question 45

aim of conformational studies

Answer 45

identiying conditions that maximize the structural stability of the native sate and prevent aggrgation

Question 46

Biologics exist in equilibrium between

Answer 46

native, partially denaturated and denaturated conformational states