Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary

Abstract

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii) summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two-day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.

New science, drug regulation, and emergent public health issues: The work of FDA’s division of applied regulatory science

“…This includes conducting applied clinical research (58-60) to fill information gaps, inform best practices, and evaluate novel omics methodologies (61). DARS also developed an evidentiary framework, the draft version of which was presented at a DARS-led public workshop (62). Division of applied regulatory science (DARS) developed and validated novel, sensitive, and specific analytical methods to support pediatric pharmacokinetic studies using dried blood spot (DBS) cards.…”

“…These studies included assessments to evaluate uses of proteomic and transcriptomic analysis of human plasma to identify novel biomarkers for biosimilar development ( 61 ). A joint FDA/Duke Margolis Workshop ( 62 ) discussed initial findings and facilitated a broader discussion on use of PD biomarkers for biosimilar development. Additional details will be reported in the January 2023 themed issue on Innovations in Biosimilars in the journal Clinical Pharmacology and Therapeutics ( 61 , 63 ).…”

“…This includes conducting applied clinical research ( 58 – 60 ) to fill information gaps, inform best practices, and evaluate novel omics methodologies ( 61 ). DARS also developed an evidentiary framework, the draft version of which was presented at a DARS-led public workshop ( 62 ).…”

Advancing Innovations in Biosimilars

“…As reported in this themed issue of Clinical Pharmacology & Therapeutics ( CPT ) on Innovations in Biosimilars ( Figure ), there is an opportunity to leverage innovations in clinical pharmacology and related disciplines to improve the efficiency of biosimilar development and approval ( Figure ). One way to do this is to leverage the use of pharmacodynamic (PD) biomarkers in clinical pharmacology studies in place of comparative clinical studies with efficacy end point(s), which is discussed in multiple articles in this issue 1–5 . These articles and others 6 also discuss how modeling and simulation (or model‐informed drug development (MIDD)) can be used to optimize study design and analyses.…”

“…Broader discussions around use of PD biomarkers occurred at an FDA and Duke Margolis Center for Health Policy public workshop in 2021, which is summarized by Florian et al 2 . The workshop identified opportunities for investing in PD biomarker research and clarifying regulatory expectations for PD biomarker acceptability.…”