Clinical requirements for extracellular vesicle assays

Abstract

The scientific and clinical interest in extracellular vesicles (EV) has grown exponentially during the past 15 years. As most research indicates that EVs can be utilised in diagnostics, prognostics and therapeutics, we may be on the brink of establishing the clinical utility of EV measurement, but how can we make this a reality? If we are to introduce EVs as biomarkers into clinical laboratories, it will be necessary to offer fully validated, International Organization for Standardization (ISO) standard 15189 assays. ISO 15189 defines the quality management system requirements particular to medical laboratories and is used internationally to determine accreditation. In order for a clinical laboratory to offer an accredited test for EVs, this assay must have been subjected to a thorough assay validation process. This process requires the generation of data related to defined performance characteristics, to ensure that an assay is performing in accordance with the needs of its clinical users. Each of the defined performance characteristics will be discussed in this review, along with the issues that specifically affect EV analysis. Accreditation is increasingly important for all clinical laboratories and the standards required to achieve this are becoming more and more stringent. Therefore, as companies seek to develop the best assays to detect EVs and their molecular contents for clinical utility, and as we move rapidly towards our goal of offering EV analysis in the diagnosis and monitoring of disease, it is timely to highlight the requirements for the clinical accreditation of such assays. It is essential to consider these parameters to ensure that we develop the highest quality assays possible and ultimately the best outcomes for patients.

The Circulating Fatty Acid Transporter Soluble CD36 Is Not Associated with Carotid Atherosclerosis in Subjects with Type 1 and Type 2 Diabetes Mellitus

“…Therefore, measuring plasma CD36 MP content may improve detection of actual CD36 concentrations. However, in contrast to ELISA, which is a well-established method, to our knowledge no protocol has been developed yet to measure CD36 MP that meets the quality standards required to be used extensively in the clinical practice [42]. Regarding the possible causes mentioned above, we did not find differences in CD36 surface expression on monocytes and leukocytes of peripheral blood among patients with vs. without carotid atherosclerotic plaque.…”

Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop

“…A major question in EV therapeutics is under what conditions the FDA, EMA and other regulatory agencies will approve therapeutic use of EVs. The clinical requirements for EV therapeutics and assays must be achieved before approval can be granted [169]. Cell‐based therapies have been approved, so there is hope for EVs in the future.…”

Urinary Biomarkers in Bladder Cancer: Where Do We Stand and Potential Role of Extracellular Vesicles

“…This would facilitate the establishment of multicentric clinical trials to validate the clinical feasibility of EV-based biomarkers. Considering this, the International Society of Extracellular Vesicles (ISEV) has been supporting several initiatives to favor the development of such SOPs [ 156 ]. Some of these initiatives includes the Minimal Information for reporting EV-related research [ 124 ], the EV TRACK: EV Transparent Reporting and Centralizing Knowledge [ 157 ], and the Clinical Wrap-Up session at ISEV2018 [ 158 ].…”