Table 1.

Examples of Regulatory Implications of Routes to Market for Medical Devices

FDA Test Designation	Staging of Assay/ Intended Use	Regulatory Implications
RUO 1	Scientific investigations Research phase Performance evaluation stage of development	No regulatory certification required Performance verification studies recommended Cannot be used for diagnostic procedures with patients
IVD	Diagnosis of disease or other conditions Sold (marketed) as kits or systems in interstate commerce Manufactured by one company and intended for use in many settings	Laboratory CLIA certification required, dependent on FDA classification. Regulatory path through FDA IVD 510k or PMA. Establishment of GLP/quality systems; analytical and clinical validation
LDT	Developed and validated by a single laboratory Offered as a commercial service for analysis of patient samples for diagnosis and treatment from a single location	Laboratory CLIA certification required, dependent on classification. Implementation of GLP/quality system procedures Analytical validation Subject to FDA enforcement discretion2 Clearance as an IVD required if a companion diagnostic test has been approved for the same analyte.
IVDMIA	Employs a combined interpretation of multiple functions in a single result, using a non-transparent derivation that cannot be independently derived or verified by the user	FDA determines oversight on a case by case basis, possible regulation as high-risk Class II device

¹Abbreviations: CLIA, Clinical Laboratory Improvement Amendments; IVD, in vitro diagnostic; IVDMIA, IVD Multivariate Index Assay; LDT, laboratory developed test; RUO, research use only. Adapted from (12, 18, 26, 34–37)

²The FDA is reevaluating regulatory oversight of LDTs, working with Center for Medicare and Medicaid Services to establish efficient, collaborative joint oversight mechanisms