(279 days)
The Healgen Series Urine Reagent Strips and Urine Analyzers are in-vitro test systems intended for qualitative and semi-quantitative analysis of Urobilinogen, Bilirubin, Ketone, Blood, Protein, Nitrite, Leucocytes, Glucose, Specific gravity, pH and Ascorbic Acid in urine. The test systems consist of the Healgen Series Reagent Strips (Healgen 10 and Healgen 11) and the Healgen 500 or Healgen 800 Urine Analyzers. The Healgen 10 and 11 strips can be read visually and instrumentally with the Healgen 500 and 800 Analyzers. The Healgen 4 reagent strip can be read visually only. The Healgen Series Urine Reagent Strips and Urine Analyzers are intended for use to detect conditions indicating possible diabetes, metabolic abnormalities, liver diseases, kidney function, and urinary tract infections. Test results can be used along with other diagnostic information to rule out certain disease states and to determine if microscopic analysis is needed.
Healgen Series Reagent strips for Urinalysis and urine analyzers are in vitro diagnostic test devices that use reagents for qualitative and semiquantitative urinalysis.
The device is composed of several color pads aligned on a strip. Each pad is employed for testing one assay item by visually or instrumentally reading the color change of the pad and comparing with the corresponding blocks on a color chart.
Healgen Series Reagent Strip provides tests for Glucose, Bilirubin, Ketone, Specific Gravity, Blood, pH, Protein, Urobilinogen, Nitrite, Ascorbic Acid and Leukocytes in Urine.
Here's an analysis of the provided text regarding the acceptance criteria and study data for the Healgen Series Reagent Strips and Analyzers for Urinalysis:
Overview:
The submission (K111999) describes the Healgen Series Reagent Strips and Analyzers, in-vitro diagnostic devices for qualitative and semi-quantitative urinalysis of various analytes. The primary goal of the submission appears to be demonstrating substantial equivalence to a predicate device (URISTK H Series Reagent Strips for Urinalysis and Dirui H-50, H-100, or H-500 Urine Analyzer). The information provided largely focuses on the analytical performance of the device rather than a clinical outcome study.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes analytical performance characteristics but does not explicitly state acceptance criteria for a "device meets acceptance criteria" study in the typical sense of a clinical trial with predefined end-points for sensitivity/specificity. Instead, it demonstrates the analytical capabilities and equivalence to a predicate device.
The tables below summarize the reported analytical performance related to:
- Analytical Limits (Cutoff): These are the thresholds at which a positive or negative result is typically determined.
- Reportable Ranges: These define the concentration ranges within which the device can provide meaningful qualitative or semi-quantitative results.
- Analytical Specificity (Interference Study): This identifies substances and their concentrations that do not affect the test results.
Table 1: Analytical Limits (Cutoffs)
| Analyte | Unit | Cutoff |
|---|---|---|
| Urobilinogen | mg/dl | 0.7 |
| Bilirubin | mg/dl | 0.7 |
| Ketone | mg/dl | 3.5 |
| Blood | cells/µL | 6.5 |
| Protein | mg/dl | 7.2 |
| Nitrite | µg/dL | 50 |
| Leukocytes | cells /µL | 10 |
| Glucose | mg/dl | 65 |
| Ascorbic Acid | mg/dl | 6.5 |
| pH | 5.6 | |
| Specific Gravity | 1.003 |
Table 2: Reportable Ranges
| Analyte | Unit | Lab Assay Range | Reportable Range |
|---|---|---|---|
| Urobilinogen | mg/dl | 0.01-18.75 | 0.2-8 |
| Bilirubin | mg/dl | 0-18.8 | 0-6 |
| Ketone | mg/dl | 0.2-350 | 0-160 |
| Blood | cells/μL | 0-350 | 0-200 |
| Protein | mg/dl | 0.3-5000 | 0-2000 |
| Nitrite | mg/dl | 5.0-2000 | Neg-Pos |
| Leukocytes | cells/μL | 0-800 | 0-500 |
| Glucose | mg/dl | 0-5500 | 0-2000 |
| Specific Gravity | 1.000-1.040 | 1.000-1.030 | |
| pH | 0-14.0 | 5.0-8.5 | |
| Ascorbic Acid | mg/dl | 1-230 | 0-100 |
Table 3: Analytical Specificity - Non-Interfering Concentrations of Substances
| Potential Interfering Substance | Concentration Not Affecting Test |
|---|---|
| Albumin | 800 mg/dL |
| Ascorbic Acid | 50 mg/dL |
| Hemoglobin | 50 mg/dL |
| Citric Acid | 50 mg/dL |
| Bilirubin | 3.0 mg/dL |
| Creatine | 8 mg/dL |
| Acetoacetate Acid | 1 mmol/L |
| Ammonium Chloride | 189 mg/dL |
| Calcium Chloride | 50 mg/dL |
| Creatinine | 800 mg/dL |
| Glucose | 2000 mg/dL |
| Glycine | 1000 mg/dL |
| KCL | 550 mg/dL |
| NaCl | 2800 mg/dL |
| Oxalic Acid | 70 mg/dL |
| Sodium Acetate | 1200 mg/dL |
| Sodium Bicarbonate | 1500 mg/dL |
| Sodium Nitrate | 0.26 mg/dL |
| Sodium Nitrite | 0.3 mg/dL |
| Sodium Phosphate | 16 mg/dL |
| Urobilinogen | 3.0 mg/dL |
| Urea | 3000 mg/dL |
| Riboflavin | 100 mg/L |
| Theophylline | 100 mg/L |
| Phenolphthalein | 1200 mg/L |
| pH | 9.0 |
| Specific gravity | 1.030 |
| Glutathione | 200mg/dL |
| Hypochlorite | 10mg/L |
| Chlorine | 1mg/dL |
| Peroxide | 1mg/L |
| Atropine | 300mg/L |
| Fructose | 5000 mg/dL |
| Lactose | 5000 mg/dL |
| Leucocytes | 800 Cell/ μL |
| Ketone | 200 mg/dL |
| Blood | 300 Cell/ μL |
| Mesna | 50mg/dL |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Precision (repeatability/reproducibility):
- Within-run: 20 replicates for each of 3 urine control levels, using strips from 3 lots.
- Within-day: 3 urine control levels analyzed in duplicate, once a day, for 10 days, using strips from 3 lots.
- Analytical Specificity: 5 test strips from each of 3 lots for each interference test.
- Sample Size for Clinical Comparison Studies: Not explicitly stated with a specific number of clinical specimens. The text only mentions "clinical comparison studies were conducted in 3 sites using the Healgen 11 Reagent Strip for Urinalysis and the predicate devices."
- Data Provenance: Not explicitly stated (e.g., country of origin). The document implies the studies were conducted to support a submission to the US FDA, but does not specify the geographic location of the clinical sites or specimen collection. The study appears to be prospective for the analytical performance evaluations (precision, specificity) as these were performed as part of the validation. The "clinical comparison studies" also imply prospective data collection for comparison purposes.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Experts: The precision study involved "6 technicians" across 3 clinical sites. No specific qualifications (e.g., years of experience, specific certifications) are provided for these technicians, nor are they explicitly stated as "experts establishing ground truth."
- Ground Truth Qualification: For the precision and analytical specificity studies, the ground truth was established by using urine controls (Bio-Rad Level 1 and Level 2) and a 3rd control with analyte concentrations around cutoff, which was created by pooling Bio-Rad controls and spiking with pure analytes. For the clinical comparison study, the "ground truth" was implicitly the result obtained by the predicate device, as the study aimed to show comparability. There is no mention of external expert consensus or a gold standard method separate from the predicate for establishing ground truth for the clinical specimens.
4. Adjudication Method for the Test Set
- No explicit adjudication method (e.g., 2+1, 3+1) is mentioned. The analytical studies used technical replication (e.g., 20 replicates, duplicates over 10 days). For the clinical comparison, the comparison was made against the predicate device, suggesting the predicate's results served as the reference for comparability.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement
- No, an MRMC comparative effectiveness study was not explicitly described in the provided text in the typical sense of measuring human reader improvement with AI assistance.
- The document mentions "visual reading" alongside "instrumental reading" for the Healgen strips and states that "comparable testing data could be obtained by intended users when using the Healgen 11 Reagent Strip for Urinalysis and the legally marketed URISTK H Series Reagent Strips for Urinalysis from Dirui." This indicates a comparison between visual and instrumental readings, and between the new device and the predicate. However, it does not detail a study specifically designed to assess human reader improvement with AI (in this case, the analyzer acting as an 'AI' for reading strips) versus without it.
- The effect size of how much human readers improve with AI vs without AI assistance is not provided or discussed. The focus is on the performance comparability of the device (both visual and instrumental readings) to a predicate device.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, a form of standalone performance was implicitly studied for the instrumental reading. The Healgen 500 and 800 Urine Analyzers use "reflectance photometry to quantitate analyte values" and provide "instrumental reading." Precision, analytical limits, and reportable ranges are characteristics of the instrument's performance (the "algorithm") when reading the strips. The "analytical specificity" study also evaluates the instrument's performance in the presence of interfering substances. While not strictly an "AI algorithm" in the modern interpretative sense, the analyzers are automated systems that perform the reading without human interpretation beyond initiating the test and reading the display.
7. The Type of Ground Truth Used
- For analytical performance (precision, reportable ranges, analytical specificity): The ground truth was based on controlled lab-prepared samples using Bio-Rad urinalysis controls and custom-spiked controls with known analyte concentrations.
- For clinical comparison studies: The ground truth was the results obtained from the predicate device (URISTK H Series Reagent Strips for Urinalysis and Dirui H-50, H-100, or H-500 Urine Analyzer).
8. The Sample Size for the Training Set
- The document does not explicitly mention a separate "training set" for an AI or machine learning model. This is consistent with the nature of reflectance photometry-based devices, which typically rely on calibrated physics-based models rather than data-driven machine learning for their primary function of quantifying color changes. The development of the reagents and the instrumental reading parameters would be based on chemical principles and extensive analytical validation rather than a distinct machine learning training set.
9. How the Ground Truth for the Training Set Was Established
- As a distinct "training set" for AI/ML is not described, the concept of establishing ground truth for it is not applicable in the context of this submission. The device's operational parameters and measurement accuracy are established through the analytical performance studies rather than a machine learning training process.
§ 864.6550 Occult blood test.
(a)
Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is blood present in such small quantities that it can be detected only by chemical tests of suspected material, or by microscopic or spectroscopic examination.)(b)
Classification. Class II (special controls). A control intended for use with an occult blood test is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.