(84 days)
The NeoLSD™ MSMS kit is intended for the quantitative measurement of the activity of the enzymes acid-9glucocerebrosidase (ABG), acid-sphingomyelinase (GAA), 8 galactocerebrosidase (GALC), agalactosidase A (GLA) and a-L-iduronidase (IDUA) in dried blood spots (DBS) from newborn babies. The analysis of the enzymatic activity is intended as an aid in screening newborns for the following lysosomal storage disorders (LSD) respectively; Gaucher Disease, Niemann-Pick A/B Disease, Krabbe Disease, Fabry Disease, and Mucopolyaccharidosis Type I (MPS I) Disease.
The NeoLSD MSMS test system uses mass spectrometry to quantitatively measure the activity of six lysosomal enzymes simultaneously from a dried blood spot sample. The NeoLSD MSMS test system is comprised of:
- NeoLSD MSMS kit, including substrates, internal standards, solutions and controls
- The QSight Instrument is comprised of:
QSight® 210 MD Mass Spectrometer O
QSight HC Autosampler MD Instrument Software O
QSight Binary Pump MD O
Simplicity Instrument control software: O
Simplicity Data Processing software (by sample): O
O PerkinElmer MSMS Workstation Data Processing Software
The NeoLSD MSMS kit evaluates enzyme activities by measuring the product generated when an enzyme reacts with a synthesized substrate to create a specific end product. The activities of the six lysosomal enzymes present in a 3.2 mm punch from a dried blood spot (DBS) are simultaneously measured by the NeoLSD MSMS kit. The punches are incubated with the assay reagent mixture which contains;
- six substrates, one corresponding to each lysosomal enzyme
- six stable-isotope mass-labeled internal standards (IS) each designed to chemically resemble each product generated
- . a buffer to maintain the reaction pH, and to carry inhibitors to limit activity from competing enzymes if present and additives to enhance the targeted enzyme reactions.
Here's a breakdown of the acceptance criteria and study information for the NeoLSD MSMS Kit, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state acceptance criteria in a dedicated table for screening performance per se, but it details the analytical performance and implies that meeting the predicate device's performance characteristics for screening, along with established analytical limits, constitutes acceptance. The "Comparison Chart" on page 6 includes some comparable metrics between the proposed and predicate device.
Below is a table summarizing the reported analytical performance, with implied acceptance criteria that the device's performance should be within acceptable clinical/analytical ranges and comparable to the predicate device.
| Performance Metric | Acceptance Criteria (Implied/General) | Reported Device Performance (QSight System) |
|---|---|---|
| Reportable Range (µmol/L/h) | Generally, a sufficiently broad and clinically relevant range. | IDUA: 0.19 – 22.3 |
| GAA: 0.31 – 25.3 | ||
| ABG: 0.79 – 20.0 | ||
| GLA: 0.80 – 20.4 | ||
| ASM: 0.16 – 13.8 | ||
| GALC: 0.20 – 7.75 | ||
| Lower Limits of Measure (LoB, LoD, LoQ) (µmol/L/h) | Limits should be clinically relevant and allow for detection of low enzyme activity associated with LSDs. Imprecision at LoQ within specified CV% limits (ABG, GLA, IDUA |
§ 862.1488 Lysosomal storage disorder newborn screening test system.
(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.