Biosimilars and Generics

Question 1

What is a Generic Medication?

Answer 1

Before generic medicines we had ‘originator’ products which are medicines that are new and have been approved for marketing in Australia

Once the patent expires, ‘generic’ products can be marketed

Question 2

A generic product is a medicine that, in comparison to the originator product:

Answer 2

Has the same quantitative composition of therapeutically active substances

Has the same pharmaceutical form

Is bioequivalent

Have the same safety and efficacy properties

Question 3

What is Biological Medicine?

Answer 3

A medicine derived from a living system that may be either sourced from nature or produced using recombinant techniques

Question 4

What are Biosimilars?

Answer 4

A biological medicine that contains a version of the active substance of an already authorised original biologic (reference product [originator]) that is similar in terms of quality, biological activity, tolerability and efficacy

Although highly similar, not identical versions of an already registered biological medicine

Question 5

Why can’t we make exact copies of the proteins that are used as biological agent drugs?

Answer 5

Complex structures

Question 6

What are Glycoproteins?

Answer 6

Protein with a sugar attached

Question 7

What does Glycosylation affect?

Answer 7

Solubility, stability (susceptibility to proteolysis), antigenicity and orientation (structure of protein)

Question 8

What are the 2 Categories of Glycoproteins?

Answer 8

N-Glycans

O-Glycosylation

Question 9

Categories of Glycoproteins: What are N-glycans?

Answer 9

Covalently attached to proteins at the amide of asparagine

Question 10

Categories of Glycoproteins: What is O-glycosylation?

Answer 10

Glycan is attached to the side chains of serine or threonine residues

Question 11

Where does Glycosylation Occur?

Answer 11

Glycosylation occurs in endoplasmic reticulum and golgi apparatus - regulated by >200 enzymes

Question 12

Most monoclonal antibodies are ____ sub-types?

Answer 12

IgG

Question 13

What is the Molecular Weight of IgG?

Answer 13

150kDa

Question 14

How many Amino Acids does IgG contain?

Answer 14

Contains over 1300 amino acids

Question 15

How many Amino Acid Chains make up a single IgG molecule?

Answer 15

4 individual amino acid chains that make up a single IgG molecules

2 heavy chains (50kDa each) and 2 light chains (25 kDa each)

16 disulfide bridges

Heavy chain with one N-glycosylation site

Several O-glycosylation sites

Question 16

What are Potential Problems with Biosimilars?

Answer 16

Altered biological activity

Changed pharmacokinetics

Altered stability

There is currently no system in place to determine formation of ADA prevalence (unregulated/unlimited switching from originator to biosimilar product) – can’t identify pattern of events

Question 17

Brand substitution by pharmacists without reference to the prescriber is permitted for PBS prescriptions where?

Answer 17

The patient agrees to the substitution

The brands are identified as being interchangeable

The prescriber has not indicated on the prescription form that substitution is not to occur

Substitution is permitted under the relevant State or Territory legislation