Practical Guidance and Key Requirements for Invitro Diagnostic Test Development Phases.

Abstract

Biomarker development phases require progressively greater test maturity to meet critical alignment for use at the downstream development phases. During discovery phase, many biomarkers may be candidates for addressing a clinical indication. Well-controlled early assay prototypes may be sufficient to identify which markers are promising test candidates to evaluate further. Advancing biomarker candidates require subsequent clinical evidence expansion consisting of smaller research level clinical studies. An analytically robust prototype is needed to assure that results are reproducible across all research study conditions. This requires vigilant QC utilization to support results validity across many research studies. With supportive clinical evidence, advancing candidates in clinical translation phase requires development of highly robust and reproducible assay formats that are analytically reliable across an extensive range of testing variables such as numerous laboratories, laboratory conditions, and manufactured test lots. Regulators and best practices require extensive processes development, kit stability establishment, extensive analytical verifications and clinical validation to support submissions, and test suitability for the clinical intended use. Rigorous analytical verifications by standardized methods are required to establish that the test's analytical attributes achieve the product requirements. Structured clinical validation requires final test/instrumentation/software configurations with final manufacturing formulas. Clinical validation requires appropriately planned clinical cohorts that align with the test's proposed clinical intended use. Formal analytical verification and clinical validation studies support regulatory submissions, and if approved support the labeling claims of the test in the package inserts of the diagnostic test.