Spring Intro 2023

16/02/2023

Hybrid Applications – Article 10(3)

• Most commonly see when it’s not technically possible to demonstrate equivalence for a “generic” via bioequivalence studies. • Frequently seen for locally acting products (creams, ointments, inhalers, active substances acting locally in the GI tract) that aren’t systemically absorbed. • Need to demonstrate in vivo equivalence based on a pharmacodynamic or clinical studies (unless “pharmaceutical equivalence” can be demonstrated). • Article 10(3) creates scope for more significant changes (vs reference product) such as new dosage form or route of administration, but not commonly used: • No regulatory protection for new preclinical/clinical studies under Article 10(3)!

The Organisation for Professionals in Regulatory Affairs

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Biosimilar Applications – Article 10(4)

Article 10(4) Directive 2001/83/EC (as amended): “Where a biological medicinal product which is similar to a reference biological product does not meet the conditions in the definition of generic medicinal products…the results of appropriate pre-clinical tests or clinical trials…must be provided” • Due to the complexity of biological molecules, it’s not possible to demonstrate it’s the “same” active substance as the reference product. • Data heavy analytical package to establish structural similarity • PK/PD studies • Clinical equivalence, safety and immunogenicity

The Organisation for Professionals in Regulatory Affairs

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