NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays

Oncology Task Force Worskhop

An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to:

  • Validating protein-based multiplex technologies (MRM mass spec and affinity array)
  • Specimen and population issues
  • Statistical issues
  • Understanding the regulatory pathway to commercialization

In follow up to the IOTF workshop, a summary report and two mock 510(k) presubmissions with FDA review comments have now just been published online in Clinical Chemistry in advance of print publication. It is anticipated that these documents will serve as a springboard for guidance to the clinical proteomics community in the regulatory clearance of protein-based multiplexed In Vitro Diagnostic (IVD) tests.

 

Analytical Validation of Protein-Based Multiplex Assays: A Workshop Report by the NCI-FDA Interagency Oncology Task Force on Molecular Diagnostics.

Rodriguez H, Tezak Z, Mesri M, Carr SA, Liebler DC, Fisher SJ, Tempst P, Hiltke T, Kessler LG, Kinsinger CR, Philip R, Ransohoff DF, Skates SJ, Regnier FE, Anderson NL, Mansfield E; on behalf of the Workshop Participants.

Clinical proteomics has the potential to enable the early detection of cancer through the development of multiplex assays that can inform clinical decisions. However, there has been some uncertainty among translational researchers and developers as to the specific analytical measurement criteria needed to validate protein-based multiplex assays. To begin to address the causes of this uncertainty, a day-long workshop titled "Interagency Oncology Task Force Molecular Diagnostics Workshop" was held in which members of the proteomics and regulatory communities discussed many of the analytical evaluation issues that the field should address in development of protein-based multiplex assays for clinical use. This meeting report explores the issues raised at the workshop and details the recommendations that came out of the day's discussions, such as a workshop summary discussing the analytical evaluation issues that specific proteomic technologies should address when seeking US Food and Drug Administration approval.

 

Protein-Based Multiplex Assays: Mock Presubmissions to the US Food and Drug Administration.

Regnier FE, Skates SJ, Mesri M, Rodriguez H, Tezak Z, Kondratovich MV, Alterman MA, Levin JD, Roscoe D, Reilly E, Callaghan J, Kelm K, Brown D, Philip R, Carr SA, Liebler DC, Fisher SJ, Tempst P, Hiltke T, Kessler LG, Kinsinger CR, Ransohoff DF, Mansfield E, Anderson NL.

As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomics Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and Drug Administration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays.