(265 days)
The GSP Neonatal Total Galactose kit is intended for the quantitative determination of total galactose and galactose-1-phosphate) concentrations in blood specimens dried on filter paper as an aid in screening newborns for galactosemia using the GSP® instrument.
The GSP Neonatal Total Galactose test system measures total galactose, i.e. both galactose and galactose-1-phosphate, using a fluorescent galactose oxidase method. The fluorescence is measured using an excitation wavelength of 505 nm and an emission wavelength of 580 nm. The GSP Neonatal Total Galactose kit contains sufficient reagents to perform 1152 assays. The kit contains Calibrators, Controls, Neonatal Total Galactose Assay Reagent 1, Neonatal Total Galactose Assay Reagent 2, Neonatal Total Galactose Assay Buffer, Neonatal Total Galactose Assay Reconstitution Solution, and Neonatal Extraction Solution.
The provided document describes the K190335 submission for the GSP Neonatal Total Galactose kit, a device used for screening newborns for galactosemia. It primarily focuses on demonstrating the substantial equivalence of the new device (3309-002U) to a previously cleared predicate device (3309-001U).
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text, with the understanding that this is a medical device clearance document, not an AI/ML model acceptance study. Therefore, some of the requested information (like number of experts for AI ground truth, MRMC study, training set details) are not directly applicable to this type of device and submission.
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the comparison to the predicate device and standard analytical performance metrics for in vitro diagnostic tests. The goal is to show that the new device performs equivalently to the predicate.
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (typically similar to predicate performance or within acceptable ranges) | Reported Device Performance (GSP Neonatal Total Galactose kit - 3309-002U) |
|---|---|---|
| Intended Use | Quantitative determination of total galactose and galactose-1-phosphate in dried blood specimens as an aid in screening newborns for galactosemia. | Same as predicate. |
| Test Methodology | Enzymatic assay | Enzymatic assay |
| Detection Method | Fluorescence – measured at 505 nm and 580 nm wavelengths | Fluorescence – measured at 505 nm and 580 nm wavelengths |
| Instrument Platform | GSP instrument, automated (K090846) | GSP instrument, automated (K090846) |
| Sample Type | Dried blood spot | Dried blood spot |
| Reportable Range | 1.15 - 50 mg/dL (Predicate) | 1.2 - 50 mg/dL |
| Limit of Blank (LoB) | 0.34 mg/dL (Predicate) | 0.3 mg/dL (17 umol/L) |
| Limit of Detection (LoD) | 0.97 mg/dL (Predicate) | 0.7 mg/dL (39 umol/L) |
| Limit of Quantitation (LoQ) | 1.15 mg/dL (Predicate) | 1.2 mg/dL (67 umol/L), defined as lowest concentration with total CV ≤ 20% |
| Calibrators | Specific values (0.5, 2.5, 5.0, 10.0, 20, 50 mg/dL) | Specific values (0.5, 2.5, 5.0, 10, 20, 50 mg/dL) |
| Total Variation (%CV) | Not explicitly stated as acceptance criteria, but demonstrates precision. | Ranged from 10.0 to 13.9 %CV |
| Linearity | Demonstrated to be linear throughout the measuring range. | Linear from 1.2 mg/dL to 50 mg/dL |
| Recovery | Not explicitly stated as acceptance criteria, but demonstrates accuracy. | Average recovery: Galactose 98%, Galactose-1-phosphate 115%, Combined 102% |
| Interference | Bias exceeding ±15% is considered significant interference. | Acetaminophen, Conjugated Bilirubin, Intralipid, Hemoglobin/Bilirubin combinations tested (see detailed tables in source for significant interference levels) |
| Hook Effect | No hook effect expected within relevant range. | No hook effect found up to 500 mg/dL |
| Method Comparison (vs. 3309-001U) | Close correlation with predicate device. | mg/dL: y = 1.00x + 0.33; 95% CI: slope (0.96; 1.04), intercept (0.25; 0.42) (n=545) |
| Overall Percent Agreement (95th percentile) | High agreement with predicate. | 98.7 % (95%CI 98.1 % - 99.1 %) |
| Positive Percent Agreement (95th percentile) | High agreement with predicate. | 87.7 % (95%CI 80.3 % - 93.1 %) |
| Negative Percent Agreement (95th percentile) | High agreement with predicate. | 99.3 % (95%CI 98.9 % - 99.6 %) |
| Overall Percent Agreement (99th percentile) | High agreement with predicate. | 99.4 % (95%CI 98.9 % - 99.6 %) |
| Positive Percent Agreement (99th percentile) | High agreement with predicate. | 74.1 % (95%CI 53.7% - 88.9 %) |
| Negative Percent Agreement (99th percentile) | High agreement with predicate. | 99.7 % (95%CI 99.3 % - 99.9 %) |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Analytical Validation (Precision, LoB, LoD, LoQ, Linearity, Recovery, Interference, Hook Effect): Various sample sizes specific to each experiment (e.g., 150 for LoB, 60 for LoD, 40 plates/80 results for repeatability, 15 plates/75 results for between-instrument, 15 plates/75 results for between-lot variation). Samples were human red blood cell enriched with galactose, human blood enriched with galactose and galactose-1-phosphate, whole blood with added substances, or contrived dried blood spot samples.
- Method Comparison:
- Comparison with 3029-0010 Neonatal Total Galactose kit (different method): n=139 samples (routine newborn screening dried blood spot samples and dried adult human whole blood samples spiked with galactose and galactose-1-phosphate).
- Comparison with 3309-001U GSP Neonatal Total Galactose kit (predicate): n=545 routine newborn screening dried blood spot samples.
- Screening Performance Study:
- Test Set Size: 2161 samples.
- Data Provenance: Conducted at one newborn screening laboratory in the United States.
- Retrospective/Prospective: The samples included "routine newborn screening dried blood spot samples" (implying prospective collection in a screening program context) and "retrospective galactosemia diagnosed screening samples" (implying retrospective identification of confirmed positive cases). Specifically, the 95th percentile analysis included 5 retrospective galactosemia diagnosed screening samples and 1 retrospective galactosemia screening sample collected 22 hours after birth. The 99th percentile analysis included 4 retrospective galactosemia diagnosed screening samples, 1 retrospective galactosemia diagnosed screening sample collected 22 hours after birth, and 1 retrospective galactosemia diagnosed screening sample collected 16 hours after birth.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This is an in vitro diagnostic (IVD) device, not an AI/ML model for image interpretation. The "ground truth" for the screening performance study is clinical diagnosis of galactosemia, or the results from the predicate device using routine newborn screening samples.
- The document does not specify the number or qualifications of experts (e.g., radiologists) in the context of establishing ground truth, as this is not a study involving subjective interpretation like medical imaging by human experts. The 'truth' is derived from the biochemical measurements and clinical outcomes associated with galactosemia screening performed by a validated screening program.
4. Adjudication Method for the Test Set:
- Not applicable in the context of an IVD device. The 'comparison' and 'screening performance' results are based on quantitative measurements by both the new device and the predicate device compared to each other, and against known clinical results (for retrospective samples). There is no "adjudication" between human readers or AI outputs in the way it's understood for image interpretation or diagnosis.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No. An MRMC study is relevant for perception tasks like image interpretation where human readers' performance is evaluated. This is an in vitro diagnostic assay that produces quantitative results. The comparison is between the new device's quantitative output and the predicate device's quantitative output, as well as their agreement on screening classification (positive/negative) against the established screening program's outcomes.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The GSP Neonatal Total Galactose kit is a standalone in vitro diagnostic system. Its performance (accuracy, precision, linearity, etc.) is measured intrinsically and compared to the predicate, independent of human operators' subjective interpretation. The "screening performance study" evaluates the device's ability to classify samples as screen positive or negative based on its quantitative output, without direct human "interpretation" of the assay result itself. Human decision-making uses this quantitative result but isn't part of the direct device performance.
7. The Type of Ground Truth Used:
- For analytical performance (Precision, LoB, LoD, LoQ, Linearity, Recovery, Interference, Hook Effect): The ground truth is established by known concentrations of analytes (galactose, galactose-1-phosphate) in spiked samples, or by established measurement principles for blank and low-level samples.
- For Method Comparison: The ground truth is the measurement obtained from the predicate device and the 3029-0010 Neonatal Total Galactose kit. This establishes agreement.
- For Screening Performance Study: The ground truth is a combination of:
- Predicate Device Results: For routine samples, the predicate device's classification (screen positive/negative) serves as the comparator.
- Clinical Diagnosis/Outcomes: For "retrospective galactosemia diagnosed screening samples," the confirmed clinical diagnosis of galactosemia (presumably through follow-up testing and clinical presentation) serves as the ultimate truth for these specific cases.
8. The Sample Size for the Training Set:
- This device is an IVD kit, not an AI/ML algorithm. Therefore, there is no "training set" in the context of machine learning. The device's calibration curve is established using known calibrators provided in the kit. The "training" of an IVD like this involves chemical formulation, assay optimization, and manufacturing process control, not data-driven learning from a "training set" like an AI model.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable, as there is no training set for this type of device. The calibrators have been prepared from human red blood cells enriched with galactose and calibrated against primary calibrators gravimetrically prepared using a U.S. Pharmacopeia Reference Standard Preparation for galactose. This establishes the "truth" for calibration.
§ 862.1310 Galactose test system.
(a)
Identification. A galactose test system is a device intended to measure galactose in blood and urine. Galactose measurements are used in the diagnosis and treatment of the hereditary disease galactosemia (a disorder of galactose metabolism) in infants.(b)
Classification. Class I.