Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice

Chia-Li Han; Chi-Ting Lai; Aaron James Reyes; Hao-Chin Yang; Jin-Ying Lu; Shyang-Rong Shih; Kuen-Yuan Chen; Andrew N Hoofnagle; Sung-Liang Yu; William Bocik; Tara Hiltke; Huan-Chi Chiu; Ching-Yi Wan; Henry Rodriguez; Victoria Zhang; Yu-Ju Chen

doi:10.1186/s12014-024-09455-y

Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice

Clin Proteomics. 2024 Feb 22;21(1):12. doi: 10.1186/s12014-024-09455-y.

Authors

Chia-Li Han¹, Chi-Ting Lai², Aaron James Reyes², Hao-Chin Yang², Jin-Ying Lu³, Shyang-Rong Shih³, Kuen-Yuan Chen⁴, Andrew N Hoofnagle⁵, Sung-Liang Yu^{6

7}, William Bocik⁸, Tara Hiltke⁹, Huan-Chi Chiu², Ching-Yi Wan², Henry Rodriguez⁹, Victoria Zhang¹⁰, Yu-Ju Chen^{11

12}

Affiliations

¹ Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. was@tmu.edu.tw.
² Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
³ Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁶ Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
⁷ Centers for Genomics and Precision Medicine, National Taiwan University, Taipei, Taiwan.
⁸ Cancer Research Technology Program, Proteome Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁹ Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD, USA.
¹⁰ Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. Victoria_Zhang@urmc.rochester.edu.
¹¹ Institute of Chemistry, Academia Sinica, Taipei, Taiwan. yujuchen@gate.sinica.edu.tw.
¹² Department of Chemistry, National Taiwan University, Taipei, Taiwan. yujuchen@gate.sinica.edu.tw.

Abstract

Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10-30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.

Keywords: Clinical laboratory improvement amendments (CLIA); Immuno-multiple reaction monitoring (iMRM) mass spectrometry; Targeted mass spectrometry; Thyroglobulin assay.