(a) Identification. A von Willebrand factor assay is a prescription device intended for the measurement of von Willebrand factor activity or von Willebrand factor size distribution in human plasma. This device is indicated to aid in the diagnosis and management of patients being evaluated for von Willebrand factor disorders in conjunction with other clinical and laboratory findings.

(b) Classification. Class II (special controls). The special controls for this device are:

(1) Design verification and validation must include:

(i) Detailed documentation of studies demonstrating acceptable, as determined by FDA, analytical performance, including, as applicable, precision, linearity, assay interference, detection capability, specimen and reagent stability, and hook effect, with a sufficient number of specimens tested in order to obtain unbiased estimates of analytical performance. For devices measuring multiple analytes, the detailed documentation must include studies demonstrating the analytical performance of the device in regard to each individual analyte, including precision, linearity, assay interference, cross-reactivity, detection capability, specimen and reagent stability, and hook effect, as applicable.

(ii) Detailed documentation of a comparison study of clinical samples demonstrating performance relative to clinically relevant and appropriate, as determined by FDA, clinically validated laboratory tests. Further, the studies must meet all of the following criteria:

(A) All eligible subjects must meet appropriate study inclusion and exclusion criteria that define the intended use population. Specimens must be representative of the intended use population(s) and must representatively cover the full range of the device output and any clinically relevant decision points, as appropriate;

(B) The study must be conducted at a minimum of three external sites representative of the intended use setting by operators representative of the intended user population;

(C) For all intended pediatric patient populations, clinical outcome validation studies must study those populations in accordance with paragraphs (b)(1)(ii)(A) and (B) of this section; and (D) Expected (reference) values for test output must be demonstrated by testing a statistically appropriate number of samples from apparently healthy normal individuals in all relevant subpopulations (i.e., blood group O and non-O, male and female, and, if applicable, pediatric and adults), as applicable to the intended use of the device.

(2) The labeling required under § 809.10(b) of this chapter must include:

(i) Limiting statements indicating, as applicable:

(A) This device should always be used in conjunction with the patient's medical history, clinical presentation, and other laboratory findings.

(B) Identification of any known interferents, including all endogenous, exogenous, technology-specific, and patient population-specific interferents, specific to the test outputs. The information must include the concentration(s) or level(s) of the interferent at which clinically significant interference was found to occur, and the concentration range or levels at which interference was not found to occur.

(ii) A detailed summary of the performance testing results of analytical and clinical performance testing, including results of concordance evaluation (overall agreement, positive percentage agreement and negative percentage agreement) as required under paragraph (b)(1) of this section.