NCI-FDA-NIST Workshop on Standards in Molecular Diagnostics

Introduction and Scope


An increasing number of diagnostic assays based on molecular genetics, epigenetics and proteomics are becoming available for cancer detection and monitoring disease progression. The introduction of these new diagnostics has brought with it a spectrum of challenges related to accuracy of performance of these tests with the ultimate goal of clinical application.

The NCI’s Early Detection Research Network (EDRN) is working on several innovative approaches in the development and validation of promising markers.  To that end, EDRN has identified a large number of candidate molecular markers in different cancers that represent both potential markers for novel diagnostics and targets for a new generation of therapeutic agents.

The EDRN has made significant progress in identifying markers through a process of well-defined methods/protocols and has developed guidelines for validation and qualification; however, many challenges in standardization remain. These challenges include: validation of the clinical and analytical performance of the biomarker(s); standardization of pre-analytical variables during specimen collection, stabilization, and processing; measuring the analytical performance of the final diagnostic assay; and meeting regulatory requirements.

The NCI in collaboration with the National Institute of Standards and Technology (NIST) and the Food and Drug Administration (FDA) are working together to affirm general principles and guidelines for robust biomarkers.  This one-day workshop assembled experts from all three agencies as well as leaders in the field of biomarker discovery and validation. The focus included: “state of the science” in standardization of molecular diagnostics; a survey of what has been successful and what remains challenging; presentations of real and mock submissions to the FDA; and discussions of future priorities.  The format included formal presentations as well as panel discussions.

Workshop Report

Division of Cancer Prevention

National Cancer Institute - National Institutes of Health

U.S. Department of Health and Human Services


NCI-FDA-NIST Workshop on Standards in Molecular Diagnostics

Friday, December 7, 2012

NIH Neuroscience Building, Room C


8:00 a.m. – 8:10 a.m.
Nadarajen A. Vydelingum, Ph.D., FACB, NCI
Welcome & Overview
8:10 a.m. – 8:25 a.m.
Barry Kramer, M.D., MPH, NCI
Introductory Remarks
8:25 a.m. – 8:45 a.m.
Sudhir Srivastava, Ph.D., MPH, NCI
Standard Reference Sets for Clinical Validation of Biomarkers

8:45 a.m. – 8:50 a.m.               Q/A

SESSION I: State of the Science

Moderators: Nadarajen A. Vydelingum, Ph.D., NCI & Lakshman Ramamurthy, Ph.D., FDA

8:50 a.m. – 9:10 a.m.


>Marc Salit, Ph.D., NIST
The Role of Standards in Realization of Robust Molecular Biomarkers

9:10 a.m. – 9:20 a.m.               Q/A

9:20 a.m. – 9:40 a.m.
Sanford Stass, M.D., University of Maryland
Standardization of Molecular Biomarker Assays from Discovery and Development to the Clinical Laboratory: Lessons Learned

9:40 a.m. – 9:50 a.m.               Q/A

9:50 a.m. – 10:05 a.m.
Lynn Sorbara, Ph.D., NCI
CLIA/CAP Standardization from the Ground Up

10:05 a.m. – 10:10 a.m.           Q/A

10:10 a.m. – 10:30 a.m.           Break

10:30 a.m. – 10:50 a.m.
Nisar A. Pampori, Ph.D., FDA
Case Study-Regulatory Aspects When Reviewing a Device – PCA3

10:50 a.m. –11:00 a.m.            Q/A

11:00 a.m. – 11:20 a.m.
Kristen Anton, MS., Dartmouth University
The Role of Bioinformatics in Standardization

11:20 a.m. –11:30 a.m.            Q/A

11:30 a.m. – 11:50 a.m.
J. Milburn Jessup, M.D., NCI
The Role of the FDA pre-IDE as a Means to Improve Clinical Assays

11:50 a.m. – 12:00 p.m.          Q/A

12:00 p.m. – 12:30 p.m. Panel Discussion I

  • Transfer of research assays to assays validated for clinical use in a CLIA/CAP environment (requirements for SOPs, etc.)
  • Lessons learned related to assay development and application from research/developmental laboratories to clinical use

Panel Members: Frederick Barr, M.D., Ph.D., NCI (Chair); Sanford Stass, M.D., University of Maryland;  Yun-Fu Hu, Ph.D., FDA.; Jim Vaught, Ph.D., NCI; Lynn Sorbara, Ph.D., NCI

12:30 p.m. – 1:30 p.m.          Lunch Break

SESSION II: What Has Worked? What Has Not? Where Are the Gaps?

Moderator: Lynn Sorbara, Ph.D., NCI

1:30 p.m. – 1:50 p.m.
Lakshman Ramamurthy, Ph.D., FDA
Pre-IDEs, IDEs and Related Submissions to FDA

1:50 p.m. – 2:00 p.m.             Q/A

2:00 p.m. – 2:30 p.m.
Daniel Chan, Ph.D., JHU/Marina Kondratovich, Ph.D., FDA
Case Study – FDA Approval of OVA 1 Blood Test (Co-presentation based on an application submitted to and approved by the FDA)

2:30 p.m. – 2:40 p.m.             Q/A

2:40 p.m. – 3:00 p.m.             Break

3:00 p.m. – 3:20 p.m.
Robert Christenson, Ph.D., University of Maryland
Standards of Operation and Best Practices for Future Biomarker Evaluation

3:20 p.m. – 3:30 p.m.              Q/A

3:30 p.m. – 3:50 p.m.
Zivana Tezak, Ph.D., FDA
Whole Genome, High Density Platforms, Standards, and New Approaches to Evaluation of Molecular Assays

3:50 p.m. – 4:00 p.m.              Q/A

4:00 p.m. – 4:20 p.m.
Federico Goodsaid, Ph.D. Vertex Pharmaceuticals
From Validation to Qualification of Biomarkers and Alternative Paths

4:20 p.m. – 4:30 p.m.               Q/A

4:30 p.m. – 4:50 p.m. Panel Discussion II

  • What has been done well on the landscape of standards in molecular diagnostics?
  • What are the remaining gaps and what needs improving?

Panel Members: Henry Rodriguez, Ph.D., NCI (Chair); Federico Goodsaid,     Ph.D.,Vertex Pharmaceuticals; Robert Christenson, Ph.D., University of Maryland;  Daniel Chan, Ph.D, John Hopkins University;  Marina V. Kondratovich Ph.D., FDA

4:50 p.m. – 5:00 p.m. Closing Remarks

Nadarajen A. Vydelingum, Ph.D., NCI

5:00 p.m. Adjournment

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