Biomarker Qualification Program

One of the areas of FDA’s focus from the Critical Path Initiative has been the creation of Drug Development Tools (DDTs), which are methods, materials, or measures that have the potential to facilitate drug development¹. FDA created a formal qualification program to support the evaluation of some of these DDTs in areas where C-Path is working including biomarkers and clinical outcome assessments. Through this program, submitters of DDTs refine the tools and submit them for a qualification assessment.

A summary of C-Path’s progress-to-date is depicted in the tables below and represent three distinct categories: Qualified Biomarkers, Biomarker Submissions and Letters of Support that have been issued for certain biomarkers that are not qualified but warrant further evaluation.

Qualified Biomarkers and Supporting Information²:

General Area

Submitter

Biomarker(s) Qualified for Specific Contexts of Use

Issuance Date with Link to Specific Guidance

Supporting Information

Nonclinical

Predictive Safety and Testing Consortium (PSTC), Nephrotoxicity Working Group (NWG)

Urinary biomarkers: Albumin, β2- Microglobulin, Clusterin, Cystatin C, KIM-1, Total Protein, and Trefoil factor-3

4/14/2008 Drug-induced Nephrotoxicity Biomarkers

Reviews


Biomarker Qualification (BQ) Submissions:

Submitter

Biomarker

Date Accepted into BQ Program

Type of Biomarker

Proposed Biomarker Utility

Qualification Stage

Critical Path Institute (C-Path), Predictive Safety Testing Consortium, (PSTC), Skeletal Muscle Working Group (SKM WG)
Contact: John-Michael Sauer

Drug-Induced Skeletal Muscle Injury Biomarkers

12/19/2009

Safety

Safety Assessment

Consultation and Advice

C-Path, PSTC, Hepatotoxicity Working Group (HWG)
Contact: John-Michael Sauer

Drug-Induced Liver Injury Biomarkers

11/13/2009

Safety

Safety Assessment

Consultation and Advice

C-Path/ Coalition Against Major Diseases (CAMD)
Contact: Diane Stephenson

Cerebral Spinal Fluid (CSF) Markers in Alzheimer’s Disease

1/25/2011

Prognostic

Patient Selection

Consultation and Advice

C-Path/ CAMD
Contact: Diane Stephenson

Baseline Hippocampal Volume Measured by MRI in Alzheimer’s Disease

1/25/2011

Prognostic

Patient Selection

Consultation and Advice

C-Path PSTC Nephrotoxicity Working Group (NWG)
Contact: John-Michael Sauer

Drug-Induced Non-Clinical Kidney Injury Biomarkers

1/26/2011

Safety

Safety Assessment

Consultation and Advice

C-Path PSTC  NWG/ Foundation for the National Institutes of Health (FNIH) Biomarkers Consiortium³  (BC)Kidney Safety Project
Contact: John-Michael Sauer

Drug-Induced Clinical Kidney Injury Biomarkers

2/24/2011

Safety

Safety Assessment

Review

C-Path/ CAMD
Contact: Diane Stephenson

Dopamine Transporter Neuroimaging Measured by Single-photon emission computed tomography (SPECT) in Parkinson’s Disease

8/11/2011

Prognostic

Patient Selection

Consultation and Advice

C-Path/ Polycystic Kidney Disease (PKD) Outcomes Consortium
Contact: Steve Broadbent

Total Kidney Volume Measured by Ultrasound Imaging, Computed Tomography (CT) scan, or Magnetic Resonance Imaging (MRI) in Autosomal Dominant PKD

2/1/2012

Prognostic

Patient Selection

Review

Issued Letters of Support to C-Path Consortia:

Submitter

Biomarkers

Area(s) for Further Evaluation

Issuance Date with Link to Letter of Support

Submitter Contact

Critical Path Institute’s (C-Path) Predictive Safety Testing Consortium (PSTC), Nephrotoxicity Working Group (NWG)

Urinary Biomarkers: Osteopontin and Neutrophil Gelatinase-associated Lipocalin (NGAL)

Early Clinical Drug Development

8/20/2014: Letter of Support (PDF)

Refer to Predictive Safety Testing Consortium Web Site

C-Path, PSTC, Skeletal Muscle Working Group (SMWG)

Serum and Plasma Biomarkers: Myosin Light Chain 3 (Myl3), Skeletal Muscle Troponin I (sTNI),  Fatty Acid Binding Protein 3 (FABP3), Creatine Kinase, Muscle Type (CK-M, the Homodimer CK-MM)

Early Clinical Drug Development

1/22/2015: Letter of Support (PDF)

Refer to Predictive Safety Testing Consortium Web Site

C-Path, Coalition Against Major Diseases Consortium (CAMD)

Cerebral Spinal Fluid (CSF) Analyte Biomarkers: Aβ1-42, Total tau, Phosphotau

Exploratory Prognostic Biomarkers for Enrichment in Early Stage Alzheimer’s Disease Clinical Trials

2/26/2015: Letter of Support (PDF)

Refer to Coalition Against Major Diseases Web Site

C-Path, CAMD

Magnetic Resonance Imaging Biomarker: Low Baseline Hippocampal Volume

Exploratory Prognostic Biomarkers for Enrichment in Early Stage Alzheimer’s Disease Clinical Trials

3/10/2015: Letter of Support (PDF)

Refer to Coalition Against Major Diseases Web Site

C-Path, CAMD

Molecular Neuroimaging Biomarker: Dopamine Transporter (DAT)

Exploratory Prognostic Biomarkers for Enrichment in Early Stage Parkinson’s Disease Clinical Trials

3/16/2015: Letter of Support (PDF)

Refer to Coalition Against Major Diseases Web Site

¹  http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm426815.htm

²  
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/ucm284076.htm

³  These letters do not connote qualification of a biomarker. They are meant to enhance the visibility of the biomarker, encourage data sharing, and stimulate additional studies. Additional   information can be found at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm434382.htm.