Biomarkers of drug-induced acute kidney injury: a regulatory perspective

ABSTRACT

Introduction: Biomarkers are one of the drug development tools that are being developed through collaborative efforts among multiple stakeholder communities to enhance the drug development process. Biomarkers of acute drug-induced renal injury as used in drug development are more commonly referred to as renal safety biomarkers, the focus of this manuscript.

Areas covered: This manuscript provides an overview of the history and evolution of the United States Food and Drug Administration’s Center for Drug Evaluation and Research’s Biomarker Qualification Program. In addition, a regulatory perspective on the potential for renal safety biomarkers to accelerate medical and pharmaceutical research is presented. The first qualification submissions (acute kidney injury biomarkers) are discussed, including how the FDA review process affected the evolution of the biomarker qualification process and the future of biomarker discovery, development, and use. This manuscript also discusses a new repository for data on novel translational safety biomarkers from drug development programs.

Expert opinion: In addition to the qualification of novel biomarkers, a key achievement of the first submission for qualification was the bringing together of multiple stakeholder communities to optimize the process. Early qualification reviews provided valuable lessons that informed an overarching approach of how to develop a biomarker for regulatory use.

KEYWORDS:

• Acute kidney injury
• biomarkers
• biomarker qualification
• drug-induced kidney injury

Article highlights

• Novel biomarkers including renal safety biomarkers have the potential to accelerate medical and pharmaceutical research. There is unmet need for biomarkers that can aid in the detection of drug induced kidney injury and early biomarker qualification efforts, led by consortium such as the PSTC of the Critical Path Institute, focused on this unmet need.

• Biomarker discovery and validation are iterative processes that require multiple studies to identify, characterize, and confirm consistency of observed associations between biomarker elevation and clinical outcomes.

• FDA in a collaborative effort with the Critical Path Institute and various consortia of pharmaceutical companies has engaged in efforts to support the development of novel biomarkers.

• FDA’s new regulatory pathway, the biomarker qualification program, has been instrumental in helping the pharmaceutical industry develop new tools that can be used to facilitate innovation in medical therapeutics. The program continues to evolve in the setting of new laws and mandates.

• The Biomarker Data Repository, launched in 2017, provides a path forward for better collaboration and should facilitate further biomarker qualifications.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer has been involved in the renal biomarker qualification process since its inception from both the PSTC and ILSI sides, so will have worked with the authors on every preclinical renal biomarker qualification. No other peer reviewers reported potential conflicts of interest.

Additional information

Funding

This paper was not funded.