(a) Identification. A lysosomal storage disorder newborn screening test system is intended to measure lysosomal enzyme levels obtained from dried blood spot specimens on filter paper from newborns as an aid in screening newborns for a lysosomal storage disorder.

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

(1) Design verification and validation must include information that demonstrates the performance characteristics of the device, including:

(i) Study results that adequately demonstrate the clinical validity of the device, which must include information supporting the link between the analyte being measured and the condition being screened. The clinical validity of the device must be demonstrated in a clinical validation study using either well-characterized prospectively or retrospectively obtained clinical specimens from the intended use population. Testing in the clinical validation study must be performed by operators representative of the types of operators intended to use the test. The study design of the clinical validation study must assess the effects of sample collection and processing steps on test performance. Confirmed positive specimens must have a diagnosis based on confirmatory diagnostic methods or clinically meaningful information regarding the status of the subject must be obtained.

(ii) The reference interval in the normal newborn population for the analyte or analytes measured by the device.

(iii) Study results demonstrating the level of carryover or drift affecting the device performance.

(iv) Study results demonstrating the concentrations of the limit of blank, limit of detection, and limit of quantitation of the device. Sample concentrations below the limit of quantitation must not be reported by the device.

(v) Study results, which must be collected using sample panels from at least three reagent lots and at least three instruments over more than 20 testing days, demonstrating the imprecision of the device. The sample panels must consist of blood spot specimens with a range of analyte concentrations that span the reportable range of the device and must include samples with concentrations in the screen positive range, samples with concentrations at each cutoff, and samples with concentration in the normal range.

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

(i) A warning that indicates that the test is not intended to diagnose lysosomal storage disorders.

(ii) A warning that indicates that test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate.

(iii) Detailed information on device performance, including the false positive rate and the false negative rate observed in the clinical study.

(iv) Information on device performance in any relevant subgroup (e.g., age of newborn at time of sample collection, birth weight, sex, gestational age, race, ethnicity) observed in the clinical study.