Biomarkers Consortium - Identification and Validation of ctDNA Quality Control Materials

Measurement of biomarkers in blood and other fluids is key to fully realizing the benefits of precision medicine. The most widely used blood-based biomarker today is circulating tumor DNA (ctDNA), and there are an increasing number of technologies to enrich, isolate, expand and interpret ctDNA. This diversity, while excellent for innovation and providing important cancer diagnostic options to patients, clinicians, and researchers, presents multiple challenges to standardized use and interpretation of assay results. A lack of standardization makes it difficult to trust and fully understand the results of each individual assay. What is urgently needed are universally recognized quality control materials that provide assurance all the testing steps were executed correctly, enable comparison between assays across different laboratories and platforms, and provide accurate results.

The ctDNA Quality Control Materials project, in partnership with commercial reference material manufacturers, seeks to develop a set of nationally recognized standards to enable the production of suitable quality control materials that can be submitted for FDA clearance for widespread use in ctDNA testing. Once successfully developed and disseminated, such reference material will provide confidence in interpretation of ctDNA biomarker assay results, paving the way for more effective clinical research, therapeutic decision-making, regulatory evaluation, and reimbursement applications.

Development and production of FDA cleared ctDNA quality control materials for use across multiple assays and platforms will provide a pathway to accelerate regulatory approval for novel liquid biopsy technologies and their employment to aid patients. In addition, the process developed to authenticate production of these quality control materials will serve as a prototype for the development and validation of reference materials for other assays evaluating genomic material.


  • Solicit support and input on the design of reference materials from stakeholders including industry, National Cancer Institute (NCI), U.S. Food and Drug Administration (FDA), National Institutes of Standards and Technology (NIST), American Society of Clinical Oncology (ASCO), College of American Pathologists and academic institutions.
  • Define key parameters and requirements for the quality control materials and intended use.
  • Work with commercial control companies to develop quality control materials.
  • Conduct analytical validation studies using the materials as they are developed and assembled into final working quality control materials.
  • Perform a clinical pilot study in internal and external academic and commercial laboratories to extend the commutability analysis and establish clinical value of the quality control materials.
  • Orchestrate, manage and submit publications on developing ctDNA quality control materials.

Results & Accomplishments


FNIH Announcement (September 24, 2019): FNIH Biomarkers Consortium Launches Project that will Standardize the Measurement of Genetic Blood Tests to Track Cancer


Public-Sector Partners
American Society of Clinical Oncology*
Association for Molecular Pathology*
Mayo Clinic*
National Cancer Institute
National Institute of Standards and Technology*
U.S. Food and Drug Administration

Private-Sector Partners
AstraZeneca Pharmaceuticals, LP*
Genentech, a member of the Roche group*
Horizon Discovery Ltd*
Janssen Research & Development, LLC*
Merck Sharp & Dohme Corp.*
Pfizer Inc*
SeraCare Life Sciences, Inc.*
Thermo Fisher Scientific*

Academic Partners
College of American Pathologists*
Dana-Farber Cancer Institute
Frederick National Laboratory for Cancer Research*
Harvard University*

*Provides financial or in-kind support for this program.

Read what the partners are saying

Collaborative Liquid Biopsy and Reference Materials Efforts

The FNIH team is entering into collaboration with several other non-profit efforts, as well as facilitating dialogue with the FDA and EMA, to coordinate standardization in the liquid biopsy space and periodically update each other on tools and resources being produced from our individual teams. We hope that this communication will allow all efforts in the space to move forward more quickly and avoid duplication. For more information please see the links below:

BloodPAC: developed a Genomic Data Commons to aggregate liquid biopsy work, now open for contribution, and developed minimum technical data elements (MTDEs) for pre-analytical variables and patient context.  
Cancer-ID: is a consortium of 40 partners across 14 European countries working to evaluate liquid biopsy technologies and guide standardization of pre-analytical requirements, protocols and results sharing.
European Liquid Biopsy Society: aims to become the leading hub for liquid biopsy research in Europe with the key goal to translate liquid biopsy assays into clinical practice for the benefit of patients. ELBS will replace the successful EU/IMI CANCER-ID consortium.
Friends of Cancer Research: has developed a framework for standardizing clinical ctDNA testing and is soliciting retrospective and prospective studies to validate the hypothesis that ctDNA is reflective of outcomes. In addition, FOCR is building a framework for best practices to measure and report TMB.  
Medical Device Innovation Consortium: is developing somatic reference samples in solid tissues.
NIBSC: is the WHO International Laboratory for Biological Standards and is producing the WHO 1st International Standards for circulating tumor DNA, intended for the calibration of kits, assays and secondary standards.

In addition to the partners named above, the group of collaborators is open to other groups who may have similarly aligned interests and would welcome them into FNIH discussions.


Dana E. Connors, Senior Project Manager, Cancer;
Stacey J. Adam, Ph.D., Director, Cancer;