(312 days)
The Miris Human Milk Analyzer (HMA) quantitatively measures the concentration of fat, carbohydrate, and protein in human milk. The Miris HMA also provides calculated values for total solids and energy. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of newborns, including preterm, and infants. This device is intended for use in healthcare by trained healthcare personnel at clinical laboratories.
The Miris Human Milk Analyzer (HMA) is a system for the quantitative measurement of fat, protein, and total carbohydrate content in human milk. The measurements of fat, protein and carbohydrate are also used in calculating the total solids and the energy content of human milk samples. The HMA unit includes a mid-infrared (mid-IR) spectroscopy system and a user interface. The user is guided by the interactive interface, via the screen, through the measurement process by use of the six-button controlled menu system. Milk samples (3 mL) are injected into the measuring unit (cuvette) via the instrument inlet using a syringe, with excess sample and waste exiting via the outlet.
The HMA device is comprised of a sample cuvette, hardware consisting of a mainboard and central processing unit (CPU) board, a display, touch button, fan, case, and consumables. The hardware consists of a mainboard with a CPU-board, detector board, and emitter board.
Here's a breakdown of the acceptance criteria and the study details for the Miris Human Milk Analyzer, based on the provided document:
Acceptance Criteria and Device Performance
The acceptance criteria are generally implied by the various performance studies conducted and the statements regarding the device's suitability for its intended use. The performance characteristics sections (L.1 and L.2) provide the reported device performance.
| Acceptance Criterion | Reported Device Performance (Summary) |
|---|---|
| Precision | Fat: Total CV% ranges from (b)(4)% to 18.66% across different samples and sites. |
| Crude Protein: Total CV% ranges from 3.00% to 9.78% across different samples and sites. | |
| True Protein: Total CV% ranges from (b)(4)% to (b)(4)% across different samples and sites. | |
| Carbohydrates: Total CV% ranges from (b)(4)% to (b)(4)% across different samples and sites. | |
| (Detailed SD and %CV for each sample at each site are provided in the document for Between Day, Within Run, Between Run, and Total precision.) | |
| Linearity/Assay Reportable Range | Fat: R² = 0.9972, Slope = 1.0119, Intercept = -0.0724 (Claimed Range: 0.6-4.0 g/100mL) |
| Crude Protein: R² = 0.9964, Slope = 0.9925, Intercept = 0.0364 (Claimed Range: 0.8-3.0 g/100mL) | |
| True Protein: R² = 0.9967, Slope = 0.9811, Intercept = 0.0647 (Claimed Range: 0.6-2.4 g/100mL) | |
| Carbohydrates: R² = 0.9854, Slope = 0.9457, Intercept = 0.5095 (Claimed Range: 6.6-8.7 g/100mL) | |
| Calibration Stability | Calibration stable for up to (b)(4) weeks. |
| Detection Limits (LoB, LoD, LoQ) | Fat: LoB=0.06, LoD=0.11, LoQ=0.41 g/100mL |
| Crude Protein: LoB=0.06, LoD=0.25, LoQ=0.42 g/100mL | |
| True Protein: LoB=0.05, LoD=0.20, LoQ=0.34 g/100mL | |
| Carbohydrate: LoB=0.04, LoD=0.35, LoQ=3.00 g/100mL | |
| Analytical Specificity (Interference) | Identified maximum concentrations for 20+ substances that do not interfere. Identified 7 substances (Citalopram, Sertraline, Ampicillin, Vancomycin, Clindamycin, Cephalexin, Pseudoephedrine) and (b)(4) which do interfere with specific analytes. |
| Accuracy (Method Comparison with Reference Method) | Fat: N=80, R²=0.99, Slope=1.11, Intercept=-0.11 |
| Crude Protein: N=112, R²=0.96, Slope=1.19, Intercept=-0.33 | |
| True Protein: N=112, R²=0.96, Slope=1.19, Intercept=-0.27 | |
| Carbohydrates: N=106, R²=0.85, Slope=0.90, Intercept=0.62 | |
| Total Solids: N=112, R²=0.96, Slope=0.97, Intercept=0.32 | |
| Bias values (g/100mL) and 95% CI are provided for low, medium, and high concentrations for each analyte. | |
| Energy Accuracy (Bomb Calorimetry) | Bias (kcal/100mL) and 95% CI are provided for energy values at 45, 70, and 110 kcal/100mL. |
| Carryover | Specific carry-over for water to milk and milk to water determined as (b)(4) and (b)(4) respectively. |
Study Details for Miris Human Milk Analyzer
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Sample size used for the test set and the data provenance:
- Precision Studies:
- Site 1: Minimum of 3 milk samples, 80 measurements per sample (20 days, 2 runs/day, 2 replicates/run).
- Sites 2 & 3: Milk samples (number not specified, but at least 4-5 based on table rows), 30 measurements per sample (5 days, 2 runs/day, 3 replicates/run).
- Provenance: "Native human milk samples." No specific country of origin is mentioned, but it's implied to be retrospective as samples are collected and then tested.
- Linearity Studies: Minimum of 12 samples of known relative concentration. Provenance not specified.
- Detection Limit Studies:
- LoB: 4 blank samples, 60 measurements (5 days, 3 replicates/day/sample).
- LoD & LoQ: 7 milk samples with low fat, and 7 samples with low protein/carbohydrate levels, 105 replicates per variable (5 days, 3 replicates/day/sample). Provenance not specified.
- Analytical Specificity (Interference) Studies: 2 milk sample pools. Provenance not specified.
- Accuracy (Method Comparison): 112 native human milk samples. Provenance not specified; implied retrospective.
- Energy Accuracy (Bomb Calorimetry): (b)(4) native human milk samples. Provenance not specified.
- Precision Studies:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- No information is provided about experts establishing ground truth. Instead, reference laboratory methods were used. The document states: "The Miris Human Milk Analyzer is traceable to certified reference materials and validated chemical methods. The validation of these chemical methods was reviewed and found to be acceptable." For the accuracy studies, "validated comparative chemical methods" and a "validated bomb calorimetric method" were used.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- There was no mention of an adjudication method in the context of expert review. For the method comparison studies, the reference method results were often a "mean of the triplicates results."
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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:
- No MRMC comparative effectiveness study was conducted. This device is an analyzer for macronutrient composition, not an AI-assisted diagnostic device for human readers.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this entire evaluation describes the performance of the device in a standalone capacity. It quantitatively measures analytes in human milk directly, without human interpretation of raw data for results. The results are then used by healthcare providers.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth was established by validated chemical reference methods and certified reference materials. For energy, a validated bomb calorimetric method was used.
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The sample size for the training set:
- The document states that the instrument is "calibrated at the manufacturer site" using "(b)(4) calibration samples designed to cover the instrument calibration range." The specific number of samples beyond this redacted information is not provided.
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How the ground truth for the training set was established:
- For the training (calibration) set, "The calibration samples are prepared, and values are assigned using validated methods." This implies that the ground truth for calibration samples is also established using reference chemical methods, similar to the method comparison studies.
§ 862.1493 Breast milk macronutrients test system.
(a)
Identification. A breast milk macronutrients test system is a device intended to quantitatively measure fat, protein, and total carbohydrate content in human breast milk. These measurements, in conjunction with other clinical assessments, may be used to aid in the nutritional management of infants.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include the following:
(i) An appropriate traceability plan, as determined by FDA, to minimize the risk of drift in the breast milk macronutrient test system results over time.
(ii) Data that demonstrate appropriate precision, as determined by FDA, of the breast milk macronutrients test system. Precision studies must include assessment of a minimum of three breast milk specimens containing different concentrations (low, medium, and high levels) of fat, carbohydrates, and protein. Precision data must include breast milk specimen measurements that are collected at a minimum of three laboratory sites.
(iii) Data that demonstrate appropriate measurement accuracy, as determined by FDA, of fat, carbohydrates, and protein in breast milk. Measurement accuracy data must include breast milk specimen measurements that are collected at a minimum of one laboratory site.
(iv) Data from studies appropriate, as determined by FDA, to demonstrate that the device is free from significant interference from substances that could be present in human milk, including hemoglobin, and medications that are used by breastfeeding subjects.
(2) The labeling required under § 809.10 of this chapter must include a limiting statement indicating that the results should be used only as an aid in the nutritional management of infants and not as the sole basis for making nutrition decisions.