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 |
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) |
Drug-Induced Skeletal Muscle Injury Biomarkers |
12/19/2009 |
Safety |
Safety Assessment |
Consultation and Advice |
|
C-Path, PSTC, Hepatotoxicity Working Group (HWG) |
Drug-Induced Liver Injury Biomarkers |
11/13/2009 |
Safety |
Safety Assessment |
Consultation and Advice |
|
C-Path/ Coalition Against Major Diseases (CAMD) |
Cerebral Spinal Fluid (CSF) Markers in Alzheimer’s Disease |
1/25/2011 |
Prognostic |
Patient Selection |
Consultation and Advice |
|
C-Path/ CAMD |
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) |
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 |
Drug-Induced Clinical Kidney Injury Biomarkers |
2/24/2011 |
Safety |
Safety Assessment |
Review |
|
C-Path/ CAMD |
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 |
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 |
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 |
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 |
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 |
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 |
Refer to Coalition Against Major Diseases Web Site |
¹ http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm426815.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.