As the first major generation of therapeutic proteins come of age and their patents expire the possibility of “generic versions” has raised. However the regulatory pathway for such “generic” drugs does not fit the complexities of therapeutic proteins. However the EMEA released guidelines on so called biosimilars (follow-on biological product in the USA), and a number of products have made it to market, we ask what are the key learning’s.

The issues to overcome:

• Large complex molecules and standard analytical methods do not allow their full physical characterisation
• Heterogenicity due to natural processes in the host cells needed for their production
• Modification introduced during production, purification, formulation and storage
• Impurities introduced during production and purification
• Production processes are dynamic and undergo continuous improvement
• Changes are accepted if similarity can be established, their is no need to be identical
• In house methods and standards are not in the public domain

The Regulations

The EMEA is the only regulator to introduce regulations, these regulations make it clear that biosimilars are not the same and are not regulated in the same was as generic drugs. The regulations hinges on clinical data, and needs to go through the centralised procedure. The regulations provide clear guidance on data requirements and quality standards that need to be established to gain market approval, the requirements include:

• Same extensive data on quality and safety as an innovative protein drug
• Supplement showing similarity in quality, safety and efficacy between biosimilar and the same reference product
• Extensive comparability exercise is required to demonstrate that the similar biological medicinal product in terms of quality, safety and efficacy to the reference medical product
• Assessment of biological properties.
• Results of biological assays
• Non-clinical and clinical focusing on Pharmacokinetic (PK), Pharmacodynamic (PD), efficacy and safety with a focus on immunogenicity

Practicle Experience

A recent product approved as a bio-similar, Retacrit has provided a number of insights into the process and how data is evaluated through the publication of its European Public Assessment Report (EPAR), the issues considered in detail included:

• Structural comparability
• Purity comparisons
• Biological activity
• PK profiles
• Clinical effect and side effects (over 600 patients were used in the studies)

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a development target, define a development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch