Introduction to biologics

Question 1

What is a biologic?

Answer 1

Any medicinal product derived from a living organism.

I.e. Insulin and human growth hormone

Question 2

What are first-generation biologics?

Answer 2

Replicas of human hormones

They are produced by transfecting human gene into a cell line that produces the biologic protein

Question 3

What are second-generation biologics?

Answer 3

‘Engineered’ proteins

Gene altered to change the structure of the biologic protein

Question 4

What are third-generation biologics?

Answer 4

Large molecules designed for a specific biological process.

Question 5

How are biologics produced?

Answer 5

Manufactured using a living cell line, a highly complex process that is difficult to replicate.
It makes the production of generic copies (biosimilars) challenging.

Question 6

What is an antibody?

Answer 6

Large protein components of the immune system.
They bind to a pathogen (antigen)
It flag’s pathogens for destruction by immune cells
or Directly inhibits the pathogen through interaction

Question 7

What is a monoclonal antibody?

Answer 7

Lab-produced antibody to mimic the natural antibodies

Question 8

What are fusion proteins? (Chimeric proteins)

Answer 8

Proteins created through the joining of two or more genes that originally coded for separate proteins.

Question 9

What are the nomenclatures of adalimumab?
-mab
-u-
-lim-
Ada-

Answer 9

-mab = monoclonal antibody
-u = fully human molecule
-lim = indicates the target is the immune system
Ada - chosen by the manufacturer

Question 10

What is Adalimumab?

Answer 10

A monoclonal antibody that inhibits TNF-alpha, an inflammatory cytokine produced by the human immune system.

Question 11

What are the nomenclatures of monoclonal antibodies? (Third segment)

• o-
• u-
• xi-
• z-

Answer 11

Third segment indicates the source:

• o- mouse
• u- human
• xi- chimeric (human and mouse)
• z- humanized (95% human)

Question 12

What are the nomenclatures of fusion proteins? (Stem)

• mab
• mib
• nib
• tnib
• cept

Answer 12

stem (last segment):

• mab = monoclonal antibody
• mib = protease/proteasome inhibitors
• nib = small molecule inhibitor
• ‘tinib’ indicates tyrosine kinase inhibitor, ‘anib’ indicates angiogensis inhibitor
• cept = receptor molecules

Question 13

What is Insulin biologic used for?

Answer 13

Diabetes mellitis (type 1), a disease characterises by failure of insulin production and high serum glucose concentration.

Question 14

What is the half life of adalimumab that is administered subcuateneously?

Answer 14

2 weeks

Question 15

What is the difference in drug interactions for biologics and small molecule drugs?

Answer 15

Biologics = rare drug interactions

small molecule drugs = common drug interactions

Question 16

what is the difference in molecular weight for biologics and small molecule drugs?

Answer 16

Biologics = High molecular weight

Small molecule drugs = Low molecular weight

Question 17

what is the difference in PK and PD properties for biologics and small molecule drugs?

Answer 17

Biologics = Complex PD, linked to PD

Small molecule drugs = Predictable PK, distinct from PD

Question 18

what is the difference in production of biologics and small molecule drugs?

Answer 18

Biologics = produced using biological processes

Small molecule drugs = chemical production

Question 19

what is the difference in selectivity between biologics and small molecule drugs?

Answer 19

Biologics = Highly selective for target

Small molecule drugs = less selective

Question 20

what is the difference in distribution between biologics and small molecule drugs?

Answer 20

Biologics = limited distribution

Small molecule drugs = distribution varies between molecules

Question 21

What is the difference in absorption between small molecule drugs and large biological molecules?

Answer 21

Small molecules = rapid absorption

Large biological molecules = shallow increase, long half-life; sustained conc. of the drug in the body

Question 22

How are biologics admininstered?

Answer 22

Subcutaneously, intravenously, intramuscularly

There are no commercially available orall routes

Question 23

Explain features of absorption of biologics.

Answer 23

Major route of absorption for biologics is lymphatics
-large molecular size precludes capillary absorption

Tmax is reached after days

Question 24

List key features of volume of distribution for biologics

Answer 24

small volume of distribution
2-4L for monoclonal antibodies

Transport to tissues is an active process

Question 25

List key features of elimination for biologics and small molecule drugs

Answer 25

small molecule drugs are commonly eliminated via hepatic metabolism steps or excretion in urine/bile

Biologics undergo:

Endocytosis - drug taken into the cell and removed from circulation

Proteolysis - antibody mediated clearance. protein is broken down into smaller polypeptides

Target-mediated clearance (decreases with saturation of target) - elimination of monoclonal antibodies through antigen specifc interactions
Formation of immune complex

Question 26

What are the nomenclatures of monoclonal antibodies? (Second segment)

• bac-
• lim-
• tum-

Answer 26

Second segment indicates the target:

• bac- bacteria
• lim- immune system
• tum- tumour