(435 days)
The SPOTCHECK® Neonatal Total Galactose Microplate Reagent Kit is for the quantitative determination of the concentration of Total Galactose (Gal) + galactose-1-phosphate (Gal-1-P)) in whole blood saturated filter paper disks, using a microplate absorbance reader or SPOTCHECK Pro. Measurements of Total Galactose are used primarily in the diagnosis and treatment of the hereditary disease galactosemia. This method is intended for in vitro diagnostic use as an aid in neonatal screening for increased concentrations of Total Galactose, and not for monitoring purposes.
The SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit is a galactose test system. It includes Extraction Solution, Enzyme Reagent, Coenzyme Reagent, Color Reagent, and Stock Standard. Total Galactose is measured colorimetrically following the completion of two enzyme assisted reactions and the color formation reaction. Patient samples of whole blood collected on standardized filter paper are placed into the wells of a 96 well filtration microplate. Extraction solution is added and samples are eluted and incubated. The contents are filtered into a clean flat-bottom microplate. Enzyme Reagent and Coenzyme Reagent are added and the plate is incubated. Color Reagent is then added and the plate is incubated. The absorbance is measured on a microplate reader at a wavelength of 600 nm for the measurement channel and 750 nm for the reference channel. Results are expressed as mg of total galactose per dL of whole blood.
The Astoria-Pacific SPOTCHECK® Neonatal Total Galactose Microplate Reagent Kit is a diagnostic device for quantitative determination of Total Galactose (Galactose + Galactose-1-Phosphate) in whole blood samples collected on filter paper disks. This information is gleaned from the provided 510(k) summary (K121101).
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary compares the performance of the SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit to a legally marketed predicate device (Accuwell Total Galactose Model No. 6020-20 EGAL, 2000 Test Kit). The criteria for acceptance are primarily demonstrated through substantial equivalence to the predicate device in various analytical performance characteristics.
| Acceptance Criterion | Predicate Device Claim | SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit Performance (Manual Process) | SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit Performance (SPOTCHECK Pro Process) |
|---|---|---|---|
| Limit of Quantitation (LoQ) | 1.5 mg/dL | 1.4 mg/dL | 1.4 mg/dL (Note: LoD for SPOTCHECK Pro is 1.3 mg/dL, LoQ set to 1.4 mg/dL for ease of use) |
| Range | 1.5 mg/dL - 50 mg/dL | 1.4 mg/dL - 50 mg/dL | 1.4 mg/dL - 50 mg/dL |
| Linearity (Correlation Coefficient R²) | Not explicitly stated (implied by comparison of range) | > 0.995 (from 0 to 50 mg/dL) | > 0.995 (from 0 to 50 mg/dL) |
| Analytical Sensitivity (Limit of Detection, LoD) | Not explicitly stated | 1.4 mg/dL | 1.3 mg/dL |
| Clinical Classification (Presumptive Positive / Negative Agreement) | Not explicitly stated for specific agreement percentage, but classification is "presumptive positive and negative (normal)" | Classification results between predicate and SPOTCHECK reagent kits were substantially equivalent. | Classification results between predicate and SPOTCHECK reagent kits were substantially equivalent. |
| Precision (Total CV) - Normal level | 9.6% (at 6.1 mg/dL) | 9.8% (at 3.5 mg/dL) | 8.2% (at 3.3 mg/dL) |
| Precision (Total CV) - Near Cutoff level | 7.8% (at 10.4 mg/dL) | 7.7% (at 10.0 mg/dL) | 6.5% (at 10.2 mg/dL) |
| Precision (Total CV) - Galactosemic level | 8.0% (at 29.4 mg/dL) | 4.8% (at 31.3 mg/dL) | 5.1% (at 33.1 mg/dL) |
| Interference (γ globulin up to 6000 mg/dL) | No significant interference | No statistically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Albumin up to 6000 mg/dL) | No significant interference (up to 10000 mg/dL) | No statistically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Bilirubin, conjugated up to 20 mg/dL) | No significant interference | No statistically or clinically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Bilirubin, unconjugated up to 20 mg/dL) | No significant interference | No statistically or clinically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Hemoglobin up to 200 mg/dL) | No significant interference (up to 20000 mg/dL) | No statistically or clinically significant increase | Not explicitly stated, implied to be same as manual |
| Interference (Lipid up to 2700 mg/dL) | No significant interference | Statistically significant interference at low (normal) concentrations; not clinically significant (up to 3264 mg/dL) | Not explicitly stated, implied to be same as manual |
| Interference (Sulfamethoxazole (SMX) up to 4 mg/dL) | Not evaluated | No statistically or clinically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Trimethoprim (TMP) up to 4 mg/dL) | Not evaluated | Statistically significant interference at low (normal) concentrations; not clinically significant | Not explicitly stated, implied to be same as manual |
| Interference (Fructose up to 25 mg/dL) | No statistically or clinically significant interference | Statistically significant interference at low (normal) concentrations; not clinically significant | Not explicitly stated, implied to be same as manual |
| Interference (Glucose up to 1200 mg/dL) | No statistically or clinically significant interference | No statistically or clinically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Ascorbate up to 3 mg/dL) | No statistically or clinically significant interference | No statistically or clinically significant interference (up to 6 mg/dL) | Not explicitly stated, implied to be same as manual |
| Interference (Mannose up to 5 mg/dL) | No statistically or clinically significant interference | No statistically or clinically significant interference | Not explicitly stated, implied to be same as manual |
| Interference (Glutathione up to 60 mg/dL) | No statistically or clinically significant interference | Statistically significant interference at low (normal) concentrations and increased response at all concentrations, which could result in a false positive | Not explicitly stated, implied to be same as manual |
Study Proving Acceptance Criteria:
The studies described in the 510(k) summary were primarily focused on demonstrating "substantial equivalence" of the SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit to a legally marketed predicate device. This is the common pathway for 510(k) clearances. The acceptance criteria are "met" if the new device performs similarly and safely to the predicate, accounting for any differences.
2. Sample Sizes Used for the Test Set and Data Provenance
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Method Comparison (Clinical Comparison Study):
- Initial routine samples: 2037 (manual method) and 2036 (SPOTCHECK Pro method).
- Manufactured elevated samples: 51.
- Supplemental retrospective confirmed galactosemic newborn specimens: 11 (from Michigan Neonatal Biobank).
- Total Test Set for Clinical Comparison:
- Manual processing: 2037 + 51 + 11 = 2099 samples (with an overall total including the supplemental study given as 2209).
- SPOTCHECK Pro processing: 2036 + 51 + 11 = 2098 samples (with an overall total including the supplemental study given as 2208).
- Data Provenance: Routine samples were analyzed at a "state screening laboratory." The 11 confirmed galactosemic newborn specimens were obtained retrospectively from the "Michigan Neonatal Biobank." This indicates that the data is predominantly retrospective and originates from multiple sources/locations within the US.
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Precision Performance:
- For the proposed device (SPOTCHECK Kit, both manual and SPOTCHECK Pro): 80 replicates for each of the three concentrations (Normal, Near Cutoff, Galactosemic). This implies 3 concentrations * 80 replicates = 240 measurements for each processing method.
- For the predicate device: 40 replicates for each of four concentrations. This implies 4 concentrations * 40 replicates = 160 measurements.
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Analytical Sensitivity (LoD/LoQ): 180 determinations were used to calculate LoD.
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Linearity and Analytical Specificity: Sample sizes are not explicitly stated as specific numbers of unique patient samples but rather as "responses of the standards" for linearity and "interference evaluated" with corresponding concentrations for specificity.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The provided document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth for this diagnostic kit.
- For the clinical comparison study, the "ground truth" for the routine samples was likely based on their classification as "routine" and the results from a legally marketed predicate device.
- For the 51 manufactured elevated samples, the "ground truth" was established by their controlled, high Total Galactose concentration during manufacturing.
- For the 11 retrospective confirmed galactosemic newborn specimens, the "ground truth" was established by their prior diagnosis of galactosemia, likely through standard clinical and laboratory diagnostic procedures (which would be the "gold standard" for the disease).
Therefore, there were no human experts forming a consensus for the test set ground truth in the way described for imaging or subjective assessment devices. The ground truth was based on the predicate device's results, manufacturing specifications, or established clinical diagnoses.
4. Adjudication Method for the Test Set
Given that the ground truth was largely based on a predicate device, manufacturing, or existing clinical diagnoses, there was no explicit adjudication method (like 2+1 or 3+1 consensus) described for resolving discrepancies in measurements or classifications. The study likely focused on agreement/correlation between the new device and the established values/predicate.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is typically associated with imaging devices where human readers interpret results, and the AI's impact on reader performance is evaluated. This device is an in vitro diagnostic reagent kit, and its performance is assessed analytically and by comparison to a predicate device and known values, not by human reader interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone performance evaluation was done. The device's performance characteristics (LoQ, LoD, range, linearity, precision, analytical specificity) were assessed directly through laboratory studies, both when processed manually and using the "SPOTCHECK Pro" automated system. These are evaluations of the algorithm/reagent system itself, independent of interpretation by human clinicians for diagnostic purposes. The device generates a quantitative numerical result.
7. Type of Ground Truth Used
The types of "ground truth" used include:
- Predicate Device Results: For routine samples in the method comparison, the results from the legally marketed predicate device served as the comparative ground truth.
- Known Concentrations/Manufacturing Specifications: For manufactured samples with elevated Total Galactose and the samples used in linearity, precision, and interference studies, the ground truth was the known, spiked, or formulated concentrations.
- Clinical Diagnosis/Outcomes Data: For the 11 retrospective confirmed galactosemic newborn specimens, the ground truth was their established clinical diagnosis of galactosemia.
8. Sample Size for the Training Set
The document is a 510(k) summary for a reagent kit that measures an analyte. This type of device does not typically involve "training sets" in the context of machine learning or AI algorithms that learn from data. Therefore, the concept of a "training set" as it applies to AI/ML is not relevant here, and no training set size is mentioned. The device's performance is based on chemical reactions and spectrophotometric measurements, not on learning from a dataset.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" does not apply to this type of diagnostic reagent kit. Therefore, the establishment of ground truth for a non-existent training set is not applicable.
§ 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.