Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability

Abstract

Background: Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry–regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties.

Objectives: This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products.

Conclusions: In the authors’ view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a ‘similar’ product. Since ‘similarity’ is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability.

Key words: :

• Approval standards
• Biosimilar
• Follow-on biologic
• Interchangeability

Transparency

Declaration of funding

This article was funded by Eli Lilly and Company.

Declaration of financial/other relationships

All authors are employees and stock holders of Eli Lilly and Company.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors gratefully acknowledge David V. Ceryak for his insightful suggestions and comments. Editorial assistance was provided by Maria C. Jimenez.