(152 days)
The GSP Neonatal Total Galactose kit is intended for the quantitative determination of total galactose (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 kit contains sufficient reagents to perform 1152 assays. 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 kit contains 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. Calibrators and Controls are also included.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Precision (Total Variation) | Ranged from 9.3% to 14.1% CV. |
| Limit of Blank (LoB) | 0.34 mg/dL |
| Limit of Detection (LoD) | 0.97 mg/dL |
| Limit of Quantitation (LoQ) | 1.15 mg/dL (defined as the lowest concentration with a total CV equal to or less than 20%). |
| Linearity | Demonstrated linear performance throughout the measuring range (from 1.15 mg/dL to 50 mg/dL). |
| Recovery | Average recovery of 109% for galactose, 117% for galactose-1-phosphate, and 103% for both combined from three contrived dried blood spot samples. |
| Interference | - Acetaminophen: Concentrations above 2.75 mg/dL caused a significant decrease (>15%) in measured total galactose. Maximum tested (5.5 mg/dL) caused a decrease of ~20-22%. |
- Conjugated Bilirubin: Concentrations above 16.6 mg/dL caused a significant decrease (>15%) in measured total galactose. At 24.9 mg/dL and above, the decrease was 100% at some total galactose concentrations.
- Intralipid: Concentrations above 250 mg/dL (at 5 and 10 mg/dL total galactose) or 375 mg/dL (at 15 mg/dL total galactose) caused a significant increase (>15%) in measured total galactose. Maximum tested (1500 mg/dL) caused an increase of ~52-77%.
- Hemoglobin (with Bilirubin): Hemoglobin levels at 198 g/L and above in combination with an elevated bilirubin level of 15 mg/dL caused a significant increase (>15%) in measured total galactose at certain total galactose concentrations. For example, at 5 mg/dL total galactose, 198 g/L Hb led to a 26.3% increase.
- Non-Interfering Substances: Unconjugated bilirubin (20 mg/dL), ß-Nicotinamide adenine dinucleotide (100 µmol/L), Glutathione (3 mmol/L), Human Serum Albumin (30 mg/mL), Ascorbate (6 mg/dL), D-glucose (1000 mg/dL), D-mannose (100 mg/dL), D-fructose (18 mg/dL), Ampicillin (152 µmol/L), and Lithium heparin (0.375 mg/ml), and Hematocrit levels from 30% to 66% (102-230 g/L Hemoglobin) were found not to interfere. |
| Screening Performance vs. Predicate (95th percentile) | Overall percent agreement = 96.0%
Positive percent agreement = 63.6%
Negative percent agreement = 97.9% |
| Screening Performance vs. Predicate (99th percentile) | Overall percent agreement = 98.8%
Positive percent agreement = 53.3%
Negative percent agreement = 99.4% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Precision Study: 7 samples, with 216 total measurements per sample (4 replicates per sample, in 27 runs over 21 days using 3 kit lots and 3 GSP instruments).
- Sample Size for LoD: 216 determinations of 4 low-level samples.
- Sample Size for LoB: 150 blank samples.
- Sample Size for Recovery: 3 contrived dried blood spot samples.
- Sample Size for Interference Studies: Not explicitly stated for each concentration, but involved various concentrations of interfering substances at three total galactose concentrations (5, 10, and 15 mg/dL).
- Sample Size for Internal Method Comparison: 141 routine screening and spiked blood spot specimens.
- Sample Size for Screening Performance Study: 2320 samples (6 confirmed positive samples and 2314 routine samples).
- Data Provenance: The screening performance study was conducted at "one newborn screening laboratory in the United States." Other non-clinical studies (precision, linearity, LoB/LoD/LoQ, recovery, interference) appear to be internal laboratory studies without specific geographic provenance mentioned, but presumably also conducted in the US or Finland (Wallac Oy headquarters). The studies were retrospective, using banked samples and contrived samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish ground truth for the test set. For the screening performance study, "6 confirmed positive samples" are mentioned, implying prior clinical diagnosis as the ground truth. The qualifications of who confirmed these positive cases or how the "routine samples" were classified as normal are not specified.
4. Adjudication Method for the Test Set
Not applicable. The document does not describe any expert adjudication process for the test set. Ground truth for confirmed positive samples likely came from clinical diagnosis.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is an in-vitro diagnostic test kit (laboratory assay) for quantitative determination, not an imaging device or AI-assisted diagnostic tool that would involve human readers interpreting results in a MRMC study.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This refers to the performance of the assay itself. The entire submission details the standalone performance of the GSP Neonatal Total Galactose kit (assay only) without human-in-the-loop interpretation beyond standard laboratory procedures and reporting. The "GSP® instrument" is automated, as stated in the comparison chart ("GSP instrument, automated").
7. The Type of Ground Truth Used
- For Analytical Performance (Precision, LoB, LoD, LoQ, Linearity, Recovery, Interference): Ground truth was established by preparing samples with known concentrations of total galactose or specific interfering substances. For example, for recovery, the "recovery of galactose, galactose-1-phosphate, and both combined was determined from three contrived dried blood spot samples," meaning these samples were prepared with known amounts.
- For Screening Performance Study: The ground truth for the 6 positive samples was "confirmed positive." This implies a clinical diagnosis of galactosemia, likely through follow-up diagnostic testing. The other 2314 samples are referred to as "routine samples" and classified as "normal" in the context of screening performance, likely based on either their negative predicate device result or their actual clinical status. The document also compares the new device's results against the predicate device's results as a reference for "Manual result."
8. The Sample Size for the Training Set
Not applicable in the conventional sense of machine learning training sets. This is a chemical assay, not an AI/ML device that requires a distinct training set for model development. The development and optimization of the assay would involve various experiments, but these are not referred to as "training sets" in this context.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI/ML model for this chemical assay. The development of the calibrators and controls (which are prepared with known concentrations of galactose and galactose-1-phosphate) serves an analogous function in ensuring accuracy and consistency of the assay.
§ 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.