Biologicals

Question 1

what are biologicals?

Answer 1

Medicinal products which are produced by or derived from a living system

Question 2

What is lipinski’s rule of 5?

Answer 2

MW < 500
Log P< 5
< 5 hydrogen bond donors
<10 hydrogen bond acceptors

Question 3

3 of the top 8 biologicals are for what?

Answer 3

Rheumatoid arthritis

Question 4

Production of therapeutic proteins relies largely on what?

Answer 4

recombinant DNA methods

Question 5

What is the easiest way to scale up therapeutic proteins?

Answer 5

Using bacteria and yeast

Question 6

What forces determine protein folding and stabilisation?

Answer 6

Hydrophobic
Electrostatic
H-bonding
VDW forces
Steric effects
Hydration
Disulphie bridges

Question 7

What are 5 possible consequences of aggregation of a protein?

Answer 7

Altered solubility
Hypo-potency
Hyper-potency
Off target binding
Patient my generate neutralising antibodies

Question 8

What are the 4 main types of protein aggregation?

Answer 8

Soluble
Insoluble
Reversible
Irreversible

Question 9

Which 8 operations may denature or aggregate proteins?

Answer 9

Freezing/thawing
Agitation
Sonication
Contact with silicone oil
Low or high pH
Low or high salt
Specific salts
Heat

Question 10

Is saline as a diluent for proteins usually okay or not okay?

Answer 10

Okay

Question 11

Is dextrose as a diluent for proteins usually okay or not okay?

Answer 11

Not okay

Question 12

Why is dextrose usually not okay as a diluent for proteins?

Answer 12

Can react with lysines on the protein surface to form Schiff’s bases relatively quickly at ambient temperatures

Question 13

What are the advantages to intravenous administration?

Answer 13

LArge doses with 100% BA
Admin can be controlled/discontinued
Immediate access to central compartment
Easy weight based dosing

Question 14

What are the disadvantages of IV administration?

Answer 14

Additional manipulation
Patient compliance
Dose diluted into prefilled IV bag-adosption
Multiple materials of construction
Agitation during transport may be significant
Risk of microbial exposure before use

Question 15

What are the advantages to subcutaneous administration?

Answer 15

Patient convenience
No compounding at pharmacy
Can incorporate autoinjector
Best if flat dosing

Question 16

What are the disadvantages to SC administration?

Answer 16

Maximum dose is lower
Cannot stop dosing once administered
BA<100%

Question 17

What are the advantages to intravitreal administration?

Answer 17

Direct site of action-100% BA

Question 18

What are the disadvantages to intravitreal administration?

Answer 18

Patient convenience

Some risk of infection immunologically privileged

Question 19

What are the advantages to buccal administation?

Answer 19

Patient convenience

Question 20

What are the disadvantages to buccal administration?

Answer 20

Drug loss < 100% BA

Variability

Question 21

What are the advantages to pulmonary pMDIs administration?

Answer 21

Local delivery, local high concentration

Question 22

What are the disadvantages to pulmonary pMDIs administration?

Answer 22

Nebulisers are large and bulky
Proteins not stable in organic solvents
Not all nebulisers are the same
Particle size distribution
Shear or air-water interface denaturation
Testing required for each nebuliser