Biopharmaceuticals - Overview and Stability

Question 1

What are biopharmaceuticals (biologics)?

Answer 1

Protein-based therapeutics including:
* Monoclonal antibodies (mAbs)
* Antibody-drug conjugates (ADCs)
* Fusion proteins
* Peptides (e.g. insulin)
* Glycoproteins
* Enzymes
* Vaccines
* Cytokines
* Gene therapy

Biopharmaceuticals are increasingly dominant in pharmaceutical markets due to targeted therapies.

Question 2

How do biologics differ from small molecules in terms of size?

Answer 2

Biologics are significantly larger than small molecules; for example, monoclonal antibodies contain approximately 20,000 atoms compared to small molecules like aspirin, which has around 21 atoms.

Question 3

What type of bonds are involved in biologics?

Answer 3

Both strong (covalent) and weak (non-covalent) bonds.

Question 4

What is the typical molecular weight of monoclonal antibodies (mAbs)?

Answer 4

Approximately 150 kDa.

Question 5

How does glycosylation affect monoclonal antibodies?

Answer 5

It affects pharmacokinetics (PK), pharmacodynamics (PD), and bioavailability.

Question 6

Define biosimilars.

Answer 6

Biologic medicine similar in quality, safety, and efficacy to an approved biologic.

Question 7

Give examples of biosimilars.

Answer 7

Examples include:
* Trastuzumab originator vs. biosimilars
* Infliximab
* Cetuximab.

Question 8

What are fusion proteins?

Answer 8

Fusion proteins consist of the Fc region of IgG fused to a target receptor, e.g. abatacept.

Question 9

What are antibody-drug conjugates (ADCs)?

Answer 9

Highly cytotoxic agents attached to monoclonal antibodies.

Question 10

What is the significance of the drug-to-antibody ratio (DAR) in ADCs?

Answer 10

Balance is critical; high DAR increases potency but also toxicity and aggregation, while low DAR results in less potency.

Question 11

Are biopharmaceuticals generally safer than cytotoxic chemotherapy?

Answer 11

True, but they still carry risks such as immunogenicity and teratogenic potential.

Question 12

What are some stability issues associated with biopharmaceuticals?

Answer 12

Reconstitution and compounding introduce degradation risks such as exposure to oxygen, metals, silicone, and water.

Question 13

List some physical degradation pathways for proteins.

Answer 13

• Aggregation
• Fragmentation
• Denaturation
• Adsorption.

Question 14

List some chemical degradation pathways for proteins.

Answer 14

• Hydrolysis
• Oxidation
• Deamidation
• Isomerization
• Reduction.

Question 15

What factors affect the stability of biopharmaceuticals?

Answer 15

Environmental factors include:
* Light
* Heat
* Freeze-thaw cycles
* Oxidative stress.

Question 16

How does container material impact biopharmaceutical stability?

Answer 16

Material types such as polypropylene, PVC, EVA, and PA can influence stability.

Question 17

What handling and formulation effects can impact biopharmaceuticals?

Answer 17

Sensitive to:
* Shaking
* Shear stress
* Filtration
* Air exposure.

Question 18

Fill in the blank: High concentration of a biopharmaceutical leads to _______.

Answer 18

more aggregation risk.

Question 19

What diluent is considered more stable for biopharmaceuticals?

Answer 19

0.9% NaCl.

Question 20

Name some protective excipients used in biopharmaceutical formulations.

Answer 20

• Chelators: DTPA, EDTA
• Detergents: Polysorbate 20/80, Poloxamer 188
• Buffers: Histidine, acetate, citrate
• Stabilisers: Sucrose, trehalose, mannitol, glycine
• Antioxidants: Methionine, histidine.