Clinical laboratories must verify (initial startup) or validate (ongoing process) instrumentation and associated databases when implementing and routinely using MALDI-TOF MS for clinical diagnostics. The purpose of verification and validation studies is to assess the instrument’s performance in each laboratory. The benefit of using an FDA-cleared instrument is that these devices have gone through rigorous clinical trials and have been extensively evaluated. As a result, the testing required to verify the instrument’s performance is minimal and well-defined.
Specific guidance for the verification of the FDA-cleared MALDI-TOF MS instruments is recommended in a Clinical and Laboratory Standards Institute (CLSI) document (M58) titled, Methods for the Identification of Cultured Microorganisms Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry, 1st Edition.8 The key parameters include accuracy, where MALDI-TOF MS results are compared to identification by reference methods and precision, where results with well-characterized strains show reproducibility of results within runs, between runs, day-to-day, and between laboratory professionals.
Organisms not included in the FDA clinically approved (CA) list must be subjected to evaluation as laboratory-developed tests (LDTs). The validation requirements for LDTs are less clear and poorly defined for MALDI-TOF MS. The design for these types of validation studies is at the discretion of the laboratory director. In a survey of several major academic medical center laboratories using LDT MALDI-TOF MS, there was some consensus for validation studies performed by each individual laboratory.9 Laboratories generally validated their LDT MALDI-TOF MS systems by testing around 1,000 total isolates comparing the MALDI identifications to conventional laboratory methods and resolving discrepancies with 16s rRNA sequencing. Laboratories performed their analyses by microorganism category. For example, gram negative, gram positive, and yeasts were all analyzed separately. CLSI's M-58 standard details a consensus procedure.
8. Clinical and Laboratory Standards Institute (CLSI). Methods for the Identification of Cultured Microorganisms Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. 1st ed. CLSI document M58. Wayne, PA: CLSI; 2017.9. Doern, CD. "Charting Uncharted Territory: A Review of the Verification and Implementation Process for Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS) for Organism Identification." Clinical Microbiology Newsletter. 2013;35(9):69–78. Available at: https://dskm.dk/onewebmedia/Verification%20of%20MALDI-TOF-MS%20for%20organism%20identification.pdf.
