Biosimilar Development Considerations for Therapeutic Proteins With Limited Systemic Exposure: A Landscape Analysis and Pathway Evaluation

Biosimilar development for therapeutic proteins (TPs) with limited systemic exposure presents distinct challenges, as the new paradigm based on comparative analytical assessments plus pharmacokinetic similarity without a comparative efficacy study (CES) is inapplicable. Of 19 TPs with limited systemic exposure, 15 are well-characterized, of which 12 have at least one CES-feasible indication. The remaining 3 may require alternative strategies, including pharmacodynamic (PD) biomarker approaches or optimized CES designs, underscoring the need for proactive regulatory engagement.