Current IVD regulatory frameworks (FDA, IVDR, etc.) allow qPCR-based assays to be validated on
uncalibrated instruments, relying on internal reproducibility rather than SI-traceable
measurement. By contrast, clinical laboratories operating under ISO 17025 or ISO 15189 must
calibrate their PCR/qPCR instruments to SI standards. This mismatch creates a traceability gap
that undermines reproducibility, scientific defensibility, and clinical reliability.
Using population-based modeling, non-calibrated validation is shown to carry ~45% failure
probability across 10,000 instruments, versus ~1–2% when SI-traceable calibration is applied.
This document outlines the regulatory paradox, quantifies the risk, and defines how ISO 20836
calibration methods and ISO/IEC 17025 traceability close the compliance gap.