Lecture 14 - biosimilars

Question 1

what is a biosimilar ?

Answer 1

A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorised original biological medicinal product (the reference product (RP)) in the UK

Question 2

wha are the concerns for using biosimilars?

Answer 2

Reduced efficacy
Increased immunogenicity

Question 3

why do we use biosimilars?

Answer 3

Reduced cost
Drives market competition
More patient accessibility

Question 4

what is the regulatory process for approval and considerations of biosimilar?

Answer 4

Analytical validation

Biosimilarity through PK/PD study and/or pivotal trials

Extrapolation is a central component of the biosimilars approval process

Question 5

what are key points for the Analytical validation of biosimilars?

Answer 5

compared to the reference product, bisimilars should have ;
same Amino acid sequence
Similar analytical profile as reference product
Same glycans, comparable level of functional glycans
Similar bioactivity
High purity
Similar stability

Question 6

what are analytical methods used to assess the quality of biologics and biosimilars

Answer 6

high order structures
post translational modifications
primary structure
biological activities
impurities
combining attributes

Question 7

biosimilarity

Answer 7

Comparable human PK/PD as the original product and Comparable efficacy, safety and immunogenicity in a sensitive indication (large effect size, adequately immunocompetent population)

Question 8

give examples of biologicals with their existing biosimilars

Answer 8

proteins - Enoxaparin
Epoetin
Filgrastim
Insulin

Monoclonal antibodies - Trastuzamab
Infliximab
Rituximab
Bevacizumab
Adalimumab

Fusion proteins - Etanercept

Question 9

what is the aim of biosimilar development ?

Answer 9

To demonstrate biosimilarity- high similarity in terms of structure, biological activity and efficacy, safety and immunogenicity profile.

Question 10

Can you define a biologic, and how this differs between the FDA and EMEA

Answer 10

• EMEA: ”A biological medicine highly similar to another biological medicine already approved in the European Union (called “reference medicine”) in terms of structure, biological activity and efficacy, safety and immunogenicity profile (the intrinsic ability of proteins and other biological medicines to cause an immune response).”
• FDA: “Biosimilars are a type of biological product that is licensed (approved) by the FDA because they are highly similar to an already FDA-approved biological product, known as the biological reference product (reference product) and have been shown to have no clinically meaningful differences from the reference product. Minor differences in clinically inactive components are allowed. But there must be no clinically meaningful differences between the biosimilar and the reference product it was compared to in terms of the safety, purity, and potency of the product