Impact of VALID Act implementation on mass spectrometry-based clinical proteomic laboratory developed tests

Abstract

Mass spectrometry (MS)-based clinical proteomic Laboratory Developed Tests (LDTs) for the measurement of protein biomarkers related to endocrinology, cardiovascular disease, cancer, and Alzheimer's disease are gaining traction in clinical laboratories due to their value in supporting diagnostic and treatment decisions for patients. Under the current regulatory landscape, MS-based clinical proteomic LDTs are regulated by Clinical Laboratory Improvement Amendments (CLIA) under the auspices of the Centers for Medicaid and Medicare Services (CMS). However, should the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act pass, it will grant the FDA greater authority to oversee diagnostic tests, including LDTs. This could impede clinical laboratories' ability to develop new MS-based proteomic LDTs to support existing and emerging patient care needs. Therefore, this review discusses the currently available MS-based proteomic LDTs and their current regulatory landscape in the context of the potential impacts imposed by the passage of the VALID Act.

Keywords: CLIA, Clinical Laboratory Improvement Amendments; Development; LC, Liquid chromatography; LDT; LDT, Laboratory developed test; MS, Mass spectrometry; Mass spectrometry; Protein biomarker; Proteomics; VALID Act; VALID Act, Verifying Accurate Leading-Edge In Vitro Clinical Test Development Act; Validation.

Fig. 1

General workflow for the LC–MS analysis of proteins in the clinical laboratory setting. The proteins in the biological specimen are submitted to either enzymatic proteolysis-aided or intact protein analysis. Given the complexity of the clinical specimen and the endogenous abundance of the target protein, antibody-based enrichment may be required. This enrichment can be integrated into different stages of the sample preparation workflow, either at the protein or peptide level. Figure created with BioRender.com.