A biomarker assay must be sufficiently validated before it can be used for patient selection and enrollment. It must be validated as a Clinical Trial Assay (CTA), essentially a prototype of a planned IVD kit or a commercialized assay. There is no single approach to validating a CTA-grade assay or CDx grade assay, and the elements generally depend on the platform being used and whether the assay is qualitative or quantitative in nature. We draw upon best practices found in FDA Guidances, CAP or CLIA guidelines, industry groups such as the Clinical Laboratory Standards Institute, advice from our IVD partners, and academic publications.

NeoGenomics has more than 100 pathologist MDs and PhDs across a broad range of expertise to guide assay development, assay transfer, and validation. Our laboratory has developed hundreds of assays across multiple technologies. We will ensure that your assay is fit-for-purpose for your drug, patient population, and intended use. Additionally, our development process uses IVD-capable platforms to ensure that commercialization and partnering with a manufacturing partner to support later-phase-development is readily supported. Our approach includes:

  • Accuracy - confirm the performance of the assay using an orthogonal methodology

  • Sensitivity and Limit of Detection - Lower limit of detection, lower limit of quantitation, and limit of the blank

  • Specificity

  • Linearity

  • Precision - repeatability of the assay across instrument runs, days, and operators, and pathologist

    • Stability

    • Expanded precision studies to support PMA submissions

    • Repeatability of the assay including the above factors plus reagent lots, different laboratories, different pathologists, and other variables

    • Pre-analytical effects

    • Interfering substances

    • Guard-banding

    • Cross-over effects

    • Extended sample stability and reagent stability

When initiating new programs, NeoGenomics presents three options for development, validation and deployment of a CTA:

LDT: A laboratory developed test is developed and validated fit-for-purpose within NeoGenomics. This is the most popular option for early-phase drug development programs because of low cost and shorter development timelines relative to an IVD kit. NeoGenomics will select a platform and appropriate reagents that are required for CDx development, manufacturing, and eventual regulatory approval. At a later stage, the assay can be bridged to an IVD kit or developed as FDA-approved LDT.

Existing IVD Kit: An existing IVD kit is an ideal solution, if it exists, as it presents an optimized assay and an established pathway to regulatory approval and commercialization. IVD kits can be re- purposed for early phase clinical trials without permission from the manufacturer. However, re-purposing these assays for a new drug is considered off-label use by the FDA and may require a separate approval for each additional indication. Many IVD manufacturers now make available RUO or IUO kits of their FDA-approved assays available for earlier-phase drug development.

Custom Manufactured IVD Kit: A collaboration with an IVD partner to develop and manufacture an IVD kit is typically pursued for later-phase development.

In all cases, the assays must be analytically validated to CTA grade and deployed in a CLIA environment before they can be used for patient selection in early-phase clinical trials. Less strenuous validation if the test is to be used for patient stratification, central confirmation, or exploratory biomarker analysis. Our scientific and regulatory team can provide guidance on an optimized approach.