Development of an approach to monitor the manufacturing consistency of HIV rapid diagnostic tests: Panel qualification and potential impact on country programs

Abstract

Although regulatory bodies have standards that manufacturers of rapid diagnostic tests (RDTs) must meet for market approval, RDTs have no specific sampling and testing standards to monitor ongoing lot production, unlike pharmaceuticals and certain devices. With the importance of accurate diagnosis for improved health outcomes, independent quality assurance testing is key to ensuring the availability of high-quality RDTs, particularly in low-resource settings. This work develops an approach for HIV RDT lot testing, involving qualification of specimens to enable testing across various RDTs (namely Determine HIV-1/2, OraQuick HIV-1/2, Bioline HIV-1/2 3.0, UniGold HIV, and HIV Ag/Ab Combo). A sampling plan and acceptance criteria were developed per lot (approximating sensitivity and specificity) based on ISO 2859–1: 1999, using the test line response to a qualified panel (disease-positive and negative specimens) as the attribute. Based on general performance of HIV RDTs, an average % defective tests allowed per lot (acceptance quality limit) of 0.65% within ISO 2859–1: 1999 was selected, where RDTs are tested with 80 positives (accept 1 / reject 2 defective results) and 80 negatives (accept 1 / reject 2 defective results) per lot. Panel qualification was conducted with 83 positive and 84 negative serum specimens to select specimens that consistently provided expected results when tested in quadruplicate with three lots per product. While all products yielded consistent results with at least 80 negative specimens, only 4 products did the same for positive specimens. With this approach, each of these 4 RDT products can be tested with the qualified 80-positive specimen panel, requiring the other product to be tested with 20 specimens in quadruplicate. Additionally, this approach was adapted to evaluate HIV antibody/antigen combination tests with Ag panel qualification using p24 samples. While panels were qualified to monitor ongoing lot consistency of HIV RDTs, this approach could be mimicked with other types of diagnostics for monitoring manufacturing consistency, field investigation, small-scale stability checks, and proficiency testing.