Biologics Exam 3

Question 1

Biologic drugs

Answer 1

medicinal agents that are derived from living systems

Question 2

Why are biologics administered parenterally?

Answer 2

B/C biologics are degraded in the GI tract

Question 3

Common forms of biologic dosage forms?

Answer 3

-solution for injection
-pen or autoinjector
-pre-filled syringe
-lyophilized powder for reconstitution

Question 4

Examples of biologics solutions for injection

Answer 4

(Raging Snobs Located Expensive Xylophonic Napkins Anxiously)
Rituximab
Synagis
Lucents
Epogen
Xgeva
NovoLog
Avastin

Question 5

Why solution formulation?

Answer 5

-simple and less expensive
-convenient for patients
-doesn’t require reconstitution
-can be inspected before administration

Question 6

CLINICAL concerns for biologics

Answer 6

efficacy
sterility (since it’s given parenterally)
side effects
pain on injection

Question 7

Dose limiting immune response

Answer 7

body will recognize recombinant drug proteins and creates antibodies against it (causing pain and anaphylaxis)

Question 8

FORMULATION CONCERNS for biologics in solution

Answer 8

-stability
-solution viscosity and ease of injection
-manufacturability

Question 9

Stability concerns

Answer 9

aggregation, chemical stability (deamination, oxidation), shelf life, storage condition

Question 10

Solution viscosity concerns

Answer 10

mAbs can be viscous and hard to push

Question 11

Manufacturability concerns

Answer 11

cost and manufacturing time

Question 12

FORMULATION VARIABLES for biologics in solution

Answer 12

-pH (rate of degradation and additives can influence stability)
-ionic strength, tonicity
-drug concentration (aggregation increases with drug conc)
-volume
-excipients (promotes interactions with water and stabilizes)
-container, closure
-storage condition

Question 13

Ways proteins aggregate

Answer 13

-chemical reaction
-colloidal interactions
-partial unfolding (most common)

Question 14

Aggregation by chemical reaction

Answer 14

when covalent bonds link aggregates

Question 15

Aggregation by colloidal interactions

Answer 15

bumping together and stick

Question 16

Aggregation by partial unfolding

Answer 16

hydrophobic regions are exposed, stick together (deathtrap for the stability of drugs)

Question 17

Protein funnel

Answer 17

want proteins to stick in their native states, we do not want amorphous aggregates or amyloid fibrils

Question 18

Epoetin and PRCA

Answer 18

EPO is used to treat anemia in renal disease, bodies forms anti-EPO antibodies resulting in PRCA (causes anemia and death)

Question 19

What to do when solution formulation doesn’t work?

Answer 19

-store in refrigerated temp
-freeze
-freeze dry
-re engineer the protein molecule
-abandon drug candidate

Question 20

Recommendations for biologics

Answer 20

-store at recommended temp
-protect from light
-avoid agitation
-examine vial for particulates
-be aware for adverse immune responses

Question 21

What is considered the medical device?

Answer 21

pen and autoinjectors

Question 22

What is considered the formulation?

Answer 22

the solution inside of the pen

Question 23

What are prefilled syringes, pens and autoinjectors called?

Answer 23

a combination product

Question 24

Advantages of prefilled syringes, pens and autoinjectors

Answer 24

-Ease of use, convenience
-Easier to transport
-Discrete
-Increased patient compliance
-Reduced risk of having a dosage error
-Reduced risk of product contamination

Question 25

Disadvantages of prefilled syringes, pens and autoinjectors

Answer 25

-Higher cost than vial and syringe -Cannot mix two drugs -There is drug waste due to priming -Greater surface-to-volume ratio which can increase aggregation risk

Question 26

Special concerns for prefilled syringes, pens and autoinjectors

Answer 26

-Higher surface-to-volume ratio -Lower total volume -Syringe lubricants, oils (which can change interaction of proteins with solid surface, hydrophobic syringe lubricants can promote greater unfolding)

Question 27

Examples of lyophilized powders for reconstitution

Answer 27

(majority are mAbs) Remicade Nulojix Orencia Herceptin Benlysta

Question 28

Advantages of lyophilized powders for reconstitution

Answer 28

-Reduced rates of chemical and physical degradation -Improved drug stability and longer shelf life -No need to be refrigerated -Can use lyophilized formulations

Question 29

Disadvantages of lyophilized powders for reconstitution

Answer 29

-Must be reconstitution prior to injection (less convenient) -More expensive and time-consuming to manufacture

Question 30

Lyophilized powders

Answer 30

"freeze drying" which is removing water by sublimation