Biosimilars

Question 1

What are biologics?

Answer 1

They are produced in genetically engineered living cells. They include therapeutic proteins, which replace or augment beneficial human proteins, and monoclonal antibodies, which can strike disease targets with enhance precision

Question 2

What are some types of biologics?

Answer 2

Hormones

Blood products

Monoclonal antibodies

Cytokines

Growth Factors

Vaccines

Gene and cellular therapies

Fusion proteins

Question 3

What is a biosimilar?

Answer 3

A biosimilar is a copy of a commercially available biopharmaceutical product that is no longer protected by patent.

It must also qualify the following statements:

Undergone rigorous analytical and clinical assessment, in comparison to its reference product

Been approved by a regulatory agency according to a specific pathway for biosimilar evaluation

Question 4

Is the active substance of a biosimilar basically the same as the original biologic?

Answer 4

Yes, only slight variations due to shear complexity and differences in manufacturing process.

Biosimilar manufacturers do not get any information from the original biologic manufacturer, they must reverse-engineer the original product into the biosimilar

Question 5

Can biosimilar have some variability vs. the original biologic?

Answer 5

Yes, as long as the differences have been shown to not affect safety or effectiveness. But a biosimilar must have the same presentation, dose, and administration mode.

Biosimilars are highly similar to the reference biologic anyways

Question 6

What are the advantages of biosimilars?

Answer 6

They require less funding to develop because they are simply revere-engineered biologics. Due to lower R&D costs, these drugs are significantly cheaper vs. the original biologic

Question 7

How do biosimilar manufacturers replicate biologics?

Answer 7

1. Characterization of reference product
2. Cell line creation
3. Cultivation and production
4. Isolation and purification
5. Formulation, fill,and finish
6. Post-marketing/post-approval

Question 8

What is identified in characterizing the reference biologic?

Answer 8

Biosimilar manufacturers attempt to quanity the original biologic product’s identity (primary and higher-order structure), purity, biological activity, and stability of a drug

Question 9

Do original biologic product manufacturers give biosimilar manufacturers what cell lines were used to make the original product?

Answer 9

No, biosimilar manufacturers must develop a custom cell line, with its own set of procedures for manufacturing from cell cultivation, protein production, purification, to formulation and packaging

Check points are located along this process to ensure the critical quality attributes of the biosimilar do not fall short of the original biologic product

Question 10

What happens after an appropriate cell line has been developed?

Answer 10

The product produced by these cells is analyzed and compared against the original biologic.

Ensure safety, potency, pharmacokinetics, and overall quality remains the in the biosimilar vs. the original biologic product

Question 11

What is the significance of post-translational modifications to proteins?

Answer 11

Ex. Addition of oligomannose glycans can effect PK properties, and reduce clearance time

Other post-translational modifications can alter the immunogenicity of a protein, impacting patient safety and efficacy

Question 12

Review slide 18 about analytical characterization and comparison of original biologic product

Question 13

How can a potential biosimilar antibody show it is biosimilar to the original biologic antibody?

Answer 13

Biosimilarity for antibodies can only be established through thorough evaluation of the biosimilar in active comparator clinical trials and experiments with the reference product.

This process occurs despite previous rigorous analysis and reverse engineering of original biologic product

Question 14

What is the major goal in biosimilar product development?

Answer 14

Major goal is to determine similarity to original biologic product

Question 15

What are the sources of variation between original biologic and biosimilar?

Answer 15

All of the following information is not given by the original biologic manufacturer to the biosimilar manufacturer

Gene sequence

Different vector

Choice of host (difference in glycosylation)

Bioreactor choice

Operating conditions

Different binding and elation conditions

Different filter suppliers

Different methods, reagents, and reference standards

Suppliers of excipients

Question 16

What are interchangeables?

Answer 16

An interchangeable product may be substituted for the reference product without the involvement of the prescriber

To receive a biosimilar instead of an interchangeable, the patient must get a prescription for the biosimilar

Question 17

Do biosimilars have to fulfill a lower standard of safety vs. original biologics?

Answer 17

No, biosimilars are manufactured to the same regulatory standards as other biologic drugs and are authorized after a scientific evaluation by Health Canada

Question 18

What is the difference between a biosimilar and a bio better?

Answer 18

Biobetters are structurally different form original licensed biopharmaceutical, but they are improvements in performance while preserving mechanism of action

Question 19

Are generic drugs analogous to biosimilars?

Answer 19

No, they are analogous to biobetters

Question 20

What are non-comparable s?

Answer 20

They are also known as bio copies, biomimics, intended copies, and non regulated biologics.

These are copies of an original biologic product that are available for sale in other countries, but they have not gone through the rigorous regulatory process of our legal jurisdiction

Non-comparables may have clinically significant differences in quality, efficacy, and safety compared to original biologic products