Building a Roadmap to Biomarker Qualification: Challenges and Opportunities

Abstract

The traditional route for regulatory acceptance of biomarkers in drug development is through submission of biomarker data in drug approval submissions in the context of a single drug development program. The US FDA's Critical Path Initiative called for establishment of a biomarker qualification process to enable progress in the drug development paradigm. In response to this, the Center for Drug Evaluation and Research (CDER) established a Biomarker Qualification Program (BQP) to qualify a biomarker for a specific context of use (COU). The qualified biomarker can then be used in multiple drug development programs for this COU without re-review. Here, we describe some of the features of the BQP and two new initiatives that have the potential to aid biomarker development through early interactions with the FDA. Finally, we discuss some of the feedback the FDA has received from submitters and the BQP's actions to strengthen the program.

Biomarker Assay Validation

“…In order to explore these concerns, this special focus issue of Bioanalysis has been dedicated to the BAV and shares with the reader scientific insights, regulatory opinions and relevant case studies of the current processes and industry standards. Moreover, this is a timely and fortuitous happenstance as a recent regulatory initiative [10] and has led to a more harmonized perception of the gaps and necessities of both the BAV and the essential prerequisites for biomarker qualification [11].In an editorial, L Stevenson (Biogen) discusses the critical concepts associated with parallelism assessments in LBA-biomarker assay development and the BAV, which has been an increasingly debated and a popular topic of discussion over recent years in the literature. Here, the key discussion points on this important topic covered in recent public workshops in the USA are described [12].The current situation on BAV in another of the major countries involved in drug development, Japan, is discussed in this issue in an editorial by Saito et al (NIH Sciences).…”

Defining Disease Modifying Therapy for Alzheimer’s Disease

“…These are low CSF Aβ42 and hippocampal atrophy as measured on magnetic resonance imaging (MRI) (23, 24). No AD biomarkers have been qualified by the FDA, and biomarkers used as outcome measures in trials of DMTs must be established as fit-for-purpose for each trial (25). …”

Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: A View of the Regulatory Science Qualification Landscape from the Coalition Against Major Diseases CSF Biomarker Team

“…Defining a COU is the cornerstone of the qualification discussion as it determines the level of evidence required to support qualification. This qualification can range from that of diagnostic biomarkers used to identify individuals with the disease or defines a subset of the disease, to prognostic biomarkers used to determine the likelihood of a clinical event, disease recurrence, or progression [2], and to predictive biomarkers that are used as enrichment biomarkers, that are reinforcing trials entry criteria to identify individuals who are more likely to respond to a drug under investigation to a monitoring biomarker that can serve as reflection of drug treatment mechanism of action or treatment outcome, that may eventually become a surrogate biomarker for clinical outcome measures [4]. The level of evidence needed for qualification depends on the category of biomarker (e.g., prognostic, predictive, monitoring, etc.)…”