CRED ERP 25

01/07/2025

Biosimilars

• Biological medicinal products, which are similar to a reference biological product but do not meet the conditions in the definition of generic medicinal products owing to differences relating to raw material or differences in manufacturing process

• Results of appropriate non-clinical or clinical studies needed

• Modules 1, 2 & 3 (complete quality data)

• Module 4 Appropriate toxicological and non-clinical data

• Module 5 – Bio-equivalence and supplemental appropriate clinical studies • Case-by-case basis for the M 4 and 5 requirements

• Comparability exercise to demonstrate similarity (establish similarity between Originator and Biosimilar to demonstrate that no clinically meaningful difference exists)

• Complexity

• Unlike NCEs, small distinctions in the cell line, the manufacturing process or the surrounding environment can make a major difference in side effects observed during treatment, i.e.: • Two similar biologics can trigger very different immunogenic response • Post translational modifications such as glycosylation

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Development of a biosimilar

• The comparability of reference and comparator must be demonstrated at all levels

• The rigorous comparability is required for therapeutic interchange

Requires a ‘different approach’ from small molecule development:

Progressive order of development

1.

2. Thorough comparison…no assumptions!

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