Evaluation of diagnostic kits and reagents-a viewpoint from the industry

Assuring the performance characteristics of in vitro diagnostics (IVDs) is a major objective of product evaluations. This includes using sets of well planned and controlled trials in order to: (i) analyze product performance characteristics; (ii) validate design specifications; and (iii) assess product safety. Performance parameters like sensitivity, specificity, precision, robustness etc. are assessed in order to assure that the product design consistently meets performance specifications upon manufacturing. Documentation on product performance can also be used for pre-market approval submissions which are required in some European countries.

Internal quality policies have the following impact on the design of evaluation trials: (i) use of at least three production lots (with final specifications); (ii) performed under field conditions and GLP; (iii) performed at different sites; (iv) analyzing clinical specimens having statistically significant numbers; (v) use of validated statistical methods/software (SAS); (6) quality-assuring documentation. External expectations influencing product evaluations include the following aspects: (i) state-of-the-art performance; (ii) technical standards like ISO, EN, DIN; (iii) Customers' needs; and (iv) regulatory requirements for the approval of IVDs.

Based on a quality system (ISO 9001), product evaluations are a major constituent in a phased development and manufacturing process of IVDs prior to market entry. Product evaluations address particular performance goals which relate to aspects outlined above including regulatory requirements. Depending on the assay type, they are displayed in absolute and relative features, e.g. (i) intra- and interassay variation below 10% for precision; (ii) no false-negatives among certified positive specimens for sensitivity; (iii) a 'true' specificity > 99.75% (lower limit of 95% CI); and (4) earlier detection of seroconversion by the 'new' assay vs. the 'old' assay etc. The basic design and the assessment of performance characteristics is described by giving particular examples.