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510(k) Data Aggregation
(265 days)
MA 02451
Re: K190335
Trade/Device Name: GSP Neonatal Total Galactose kit Regulation Number: 21 CFR 862.1310
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| Regulation: | 21 CFR 862.1310
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.
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(152 days)
GSP Neonatal Total Galactose kit (3309-001U) Common Name: Galactose test system Regulation: 21 CFR 862.1310
MA 02451
Rc: K133652
Trade/Device Name: GSP Neonatal Total Galactose Kit Regulation Number: 21 CFR 862.1310
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.
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(435 days)
Name of the Device
Product Classification
| Regulation Number | 21 CFR 862.1310
Product Classification
| Regulation Number | 21 CFR 862.1310 |
|---|---|
| Trade/Device Name: SPOTCHECK Neonatal Total Galactose Microplate Reagent Kit Regulation Number: 21 CFR 862.1310 |
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
-
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.
-
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.
-
Analytical Sensitivity (LoD/LoQ): 180 determinations were used to calculate LoD.
-
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.
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(416 days)
| Galactose Test System (21 CFR 862.1310
20750, Finland
Re: K071649
Trade/Device Name: Neonatal Total Galactose Kit Regulation Number: 21 CFR 862.1310
This 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.
The Neonatal Total Galactose kit makes use of a fluorescent galactose oxidase method. The assay measures total galactose, i.e. both galactose and galactose-1-phosphate.
The provided information describes a medical device called the "Neonatal Total Galactose Kit" and its performance in a substantial equivalence study as submitted for 510(k) clearance (K071649).
Here's an analysis of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The submission focuses on demonstrating substantial equivalence to a predicate device (BioRad QuantaseTM Neonatal Total Galactose Screening Assay, K990654) rather than explicit acceptance criteria for a novel performance claim alone. However, performance characteristics are compared, which implicitly serve as acceptance benchmarks against the predicate.
For the purpose of this analysis, "acceptance criteria" are interpreted as the comparable performance metrics of the predicate device that the new device aims to match or demonstrate equivalency to. "Reported device performance" refers to the results obtained for the Neonatal Total Galactose Kit.
| Performance Metric | Predicate Device Performance | Neonatal Total Galactose Kit Performance | Acceptance Criteria (implied, based on predicate) |
|---|---|---|---|
| Analytical Sensitivity | 0.60 mg/dL | 1.3 mg/dL | Performance comparable to 0.60 mg/dL |
| Linearity | 0.6 to 55 mg/dL | 1.3 to 56 mg/dL | Performance comparable to 0.6 to 55 mg/dL |
| Measuring Range | 0.6 to 50 mg/mL | 1.3 to 40 mg/mL | Performance comparable to 0.6 to 50 mg/mL |
| Specificity/Recovery (D(+) galactose) | Mean recovery: 95.07% (S.D: 7.49%) in presence of various sugars/metabolites | Mean recovery: 79-81% in presence of galactose, galactose-1-phosphate or both | High recovery and low interference. Results within a clinically acceptable range compared to predicate. |
| Interference | No interference with known antibiotics, non-antibiotics, and metabolites | No interference with glucose, mannose, fructose, ascorbate, bilirubin, hemoglobin, protein BSA, and acetaminophen. Interference with Glutathione (60 mg/dL) and lipemic samples (0.25 - 1 g/dL). | Comparable lack of significant interference with common substances. Specific identified interferences for the new device must be manageable. |
| Intra-assay Precision (%CV) | Low: 3.94% (at 33.96 mg/dL) | Low: 5.3% (at 20.2 mg/dL) | Comparable or improved precision. |
| Total Assay Precision (%CV) | Low: 6.27% (at 6.97 mg/dL) | Low: 8.4% (at 23 mg/dL) | Comparable or improved precision. |
| Method Comparison (Correlation) | N/A (this is the predicate) | y = 0.6Sx + 1.73, r = 0.87 (n = 842) | Sufficient correlation with the predicate device (r > 0.85 is often considered acceptable). |
| Screening Summary (95th percentile) | Overall Percent Agreement: N/A | Positive agreement: 64% (73/114). Overall percent agreement: 95.9% ((73+1956)/2116). | High agreement with predicate for screening purposes. |
| Screening Summary (99th percentile) | Overall Percent Agreement: N/A | Positive agreement: 72.4% (21/29). Overall percent agreement: 99.2% ((21+2078)/2116). | High agreement with predicate for screening purposes, particularly at higher cut-offs. |
| True Positive Detection | Detected 3/3 true positives | Detected 3/3 true positives (at varying concentrations) | Detection of all known true positive cases. |
Note: The analytical sensitivity, linearity, and measuring range are numerically different between the predicate and the new device. The acceptance is implicitly based on these ranges being clinically acceptable for newborn screening and demonstrating equivalence in the overall clinical screening performance.
2. Sample Size Used for the Test Set and Data Provenance
Sample Size:
- Method Comparison: 842 samples for correlation analysis.
- Cut-off Value Determination & Screening Summary: 2109 routine newborn screening dried blood specimens + 7 retrospective specimens (3 diagnosed true positives for galactosemia), totaling 2116 samples.
Data Provenance:
- Country of Origin: The samples represented an "US population."
- Retrospective/Prospective: Primarily retrospective, using "routine newborn screening dried blood spot specimens" and "retrospective specimens."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The documentation does not specify the number or qualifications of experts used to establish the ground truth for the test set.
4. Adjudication Method for the Test Set
The documentation does not describe an adjudication method for the test set. The "ground truth" for the test set appears to be based on "diagnosed galactosemia" and routine screening results (implied by the comparison against a predicate device's findings).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study concerns an in-vitro diagnostic kit for measuring an analyte, not typically a visual interpretation task where human readers are involved. Therefore, there's no "human readers improve with AI vs. without AI assistance" effect size to report.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the study describes a standalone device performance. The Neonatal Total Galactose Kit is an in-vitro diagnostic assay. Its performance (analytical sensitivity, linearity, precision, method comparison, and screening summaries) is evaluated as the device itself, separate from human interpretation, although the results would be used by clinicians for decision-making.
7. The Type of Ground Truth Used
The ground truth implicitly used for the screening summary tables (which included "Diagnosed galactosemia") seems to be clinical diagnosis or outcomes data for the "true positives." For the majority of routine samples, the ground truth for comparison is the result obtained from the predicate device.
8. The Sample Size for the Training Set
The documentation does not explicitly mention a separate "training set" or its sample size. The studies described are performance evaluation studies for regulatory submission, typically focusing on validation rather than algorithm training for AI/ML devices. For IVD kits, the "development" or "optimization" phase might use internal samples, but these are not usually referred to as a "training set" in the context of the 510(k) submission.
9. How the Ground Truth for the Training Set Was Established
As no training set is explicitly mentioned, the method for establishing its ground truth is also not described. For a traditional IVD kit, the "ground truth" for calibrators and controls (which might be seen as analogous to training data in a broader sense) would be established through a traceable reference method or gravimetric preparation with certified materials.
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