(41 days)
HiChem Phosphorus Reagent is intended for the quantitative determination of inorganic phosphorus in serum, plasma and urine for the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance.
The HiChem Phosphorus Reagent determines phosphorus by its reaction with molybdate in an acidic solution to form a phosphomolybdate complex. The resulting increase in absorbance at 340 nm is proportional to the phosphorus concentration in the sample.
The HiChem Phosphorus Reagent is an adaptation of the method first described by Simonsen and is intended for use with manual spectrophotometers or clinical analyzers which can automate the required manipulations.
Here's a breakdown of the HiChem Phosphorus Reagent device's acceptance criteria and the study information as detailed in the provided document:
This document describes a diagnostic reagent, not an AI/ML powered device, therefore some of the requested information (like MRMC studies, number of experts for ground truth, adjudication methods) is not applicable. I will provide the information that is applicable based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Manual Procedure) | Reported Device Performance (Manual Procedure) | Acceptance Criteria (SYNCHRON CX® Systems) | Reported Device Performance (SYNCHRON CX® Systems) |
|---|---|---|---|---|
| Linearity Range | 0.1 - 15 mgP/dL | 0.1 - 15 mgP/dL (Linear) | 1.0 - 12.0 mgP/dL | At least 1.0 - 12.0 mgP/dL (Linear) |
| r² (Correlation) | Implied high correlation | 1.000 (Manual) | Implied high correlation | 1.000 (SYNCHRON CX®) |
| Sensitivity | 0.1 mgP/dL (Claimed) | 0.05 mgP/dL (Observed, < 0.1 mgP/dL) | 0.1 mgP/dL (Claimed) | 0.3 mgP/dL (Observed, > 0.1 mgP/dL, but sensitivity claim is 1.0 mgP/dL. There seems to be a discrepancy in the original text where it states "well below the claimed limit of 0.1 mgP/dL" after stating the sensitivity claim is 1.0 mgP/dL. I will assume the 1.0 mgP/dL is the correct claim for the SYNCHRON CX® system and 0.3 mgP/dL is well below that.) |
| Precision (Within-run SD) | Implied low variation | 0.02 - 0.07 mgP/dL (Serum) 0.00 - 0.06 mgP/dL (Urine) | Implied low variation | 0.08 - 0.11 mgP/dL (Serum) 0.08 - 0.11 mgP/dL (Urine) |
| Precision (Total SD) | Implied low variation | 0.03 - 0.08 mgP/dL (Serum) 0.00 - 0.07 mgP/dL (Urine) | Implied low variation | 0.09 - 0.13 mgP/dL (Serum) 0.11 - 0.13 mgP/dL (Urine) |
| Comparison to Predicate (r²) | Implied high correlation to predicate | 0.985 (Serum/Plasma), 0.999 (Urine) | Implied high correlation to predicate | 0.972 (Serum/Plasma), 0.996 (Urine) |
| Chemical Additive Bias | < 0.1 mgP/dL | < 0.1 mgP/dL | < 0.15 mgP/dL | < 0.15 mgP/dL |
| Calibration/Reagent Stability | Not explicitly stated in criteria for manual, but demonstrated. | Documented via assay of controls/pools | Implied stable results over claimed periods | Imprecision < 0.3 mgP/dL or 3% (manufacturer's claim) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Linearity Standards:
- Manual procedure: Data from "linearity standards" (number not explicitly stated, but regression done with df = 23, suggesting 24 data points or more).
- SYNCHRON CX® Systems: 6 linearity standards were used.
- Precision Studies:
- Manual procedure: 30 replicates for each of 2 serum controls and 2 urine pools.
- SYNCHRON CX® Systems: 60 replicates for each of 3 serum controls and 2 urine pools.
- Sensitivity determination: 30 replicates of a diluted serum control.
- Comparison to Predicate Device:
- Manual procedure: 95 mixed serum and plasma specimens, and 44 urine specimens.
- SYNCHRON CX® Systems: 153 mixed serum and plasma specimens.
- Chemical Additives: Spiked and unspiked serum pools (number not specified).
- Calibration/Reagent Stability (SYNCHRON CX® Systems): Serum controls and urine pools were assayed over claimed periods (number of samples/pools not specified).
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, such studies for in vitro diagnostics are typically conducted in a laboratory setting under controlled conditions. The studies are prospective in the sense that they are specifically designed to test the performance of the new reagent.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
Not applicable. This is a chemical reagent, and the "ground truth" for phosphorus concentration is established by the reference method (predicate device, or the actual concentration of spiked standards), not by expert consensus or interpretation.
4. Adjudication Method for the Test Set
Not applicable. The comparisons are quantitative measurements against either known standards or a legally marketed predicate device, not subjective interpretations requiring adjudication.
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 reagent, not an AI-powered diagnostic imaging or interpretation tool. There are no human readers involved in the "interpretation" of the phosphorus concentration in the same way there would be for an AI-assisted diagnostic.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, in essence, the entire study is "standalone" performance. The HiChem Phosphorus Reagent, once integrated with a spectrophotometer or clinical analyzer, performs its function (quantifying phosphorus) without human intervention in the measurement process itself. The performance data presented (linearity, precision, correlation to predicate) is the standalone performance of the reagent.
7. The Type of Ground Truth Used
The ground truth for this device is established by:
- Known concentrations: For linearity standards and sensitivity studies, the ground truth is the known, pre-determined concentration of phosphorus in the prepared standards.
- Reference method/device: For comparison studies, the "ground truth" (or reference) is the measurements obtained from the legally marketed predicate devices (BMD® Phosphorus Reagent on the Hitachi® 704 and Beckman® SYNCHRON® Systems Phosphorus Reagent on the SYNCHRON CX® Systems). The comparison aims to show substantial equivalence to these established methods.
8. The Sample Size for the Training Set
Not applicable. This is a chemical reagent and does not involve AI/Machine Learning models that require training sets in the computational sense. The "training" in developing such a reagent would be chemical formulation and optimization, not data-driven model training.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" in the context of AI/ML for this device.
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Image /page/0/Picture/1 description: The image shows the logo for HiChem Diagnostics. The logo consists of a black circle at the top, followed by the words "Smart Solutions" in a smaller font. Below that is the word "HiChem" in a bold, sans-serif font, and below that is the word "DIAGNOSTICS" in a smaller, sans-serif font.
SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS INFORMATION
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
HiChem Phosphorus Reagent is intended for the quanitiation of inorganic phosphorus in serum, plasma and urine. Measurements of inorganic phosphorus are used in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance.
The HiChem Phosphorus Reagent determines phosphorus by its reaction with molybdate in an acidic solution to form a phosphomolybdate complex. The resulting increase in absorbance at 340 nm is proportional to the phosphorus concentration in the sample.
The HiChem Phosphorus Reagent is an adaptation of the method first described by Simonsen and is intended for use with manual spectrophotometers or clinical analyzers which can automate the required manipulations.
The HiChem Phosphorus Reagent is substantially equivalent to the BMD® Phosphorus Reagent, product no. 857427, manufactured by Boehringer Mannheim Corp., Indianapolis, IN., and the Beckman® SYNCHRON® Systems Phosphorus Reagent, product no. 465145, manufactured by Beckman® Instruments, Brea, CA. All three reagents support the same intended use and produce equivalent results with the same clinical purpose. In addition, they are all based on the same methodology which determines inorganic phosphorus through the colorimeric measurement of the phosphomolybdate complex produced in an acidic reagent.
The effectiveness of the manual procedure is shown by the recovery of linearity standards, the precision of control recoveries, the comparison of serum, plasma and urine recoveries to the BMD® Phosphorus Reagent and the validation of the chemical additives and sensitivity claims.
The recovery of inorganic phosphorus using HiChem Phosphorus Reagent as a manual procedure is linear between 0.1 and 15 mgP/dL as shown by the recovery of linearity standards which span the claimed linear range. Regression statistics are shown below.
(HiChem Recoveries) = 0.1 mgP/dL + 1.004 × (Standard Conc.), r2 = 1.000, sv.x = 0.10 mgP/dL, df = 23
Precision, demonstrated by replicate assay of urine pools and commercially available control sera, is shown below.
| Specimen | n | mean | within-run SD | total SD |
|---|---|---|---|---|
| Serum control 1 | 30 | 2.09 mgP/dL/L | 0.02 mgP/dL | 0.03 mgP/dL |
| Serum control 2 | 30 | 6.17 mgP/dL/L | 0.07 mgP/dL | 0.08 mgP/dL |
| Urine Pool 1 | 30 | 2.10 mgP/dL/L | 0.00 mgP/dL | 0.00 mgP/dL |
| Urine Pool 2 | 30 | 10.43 mgP/dL/L | 0.06 mgP/dL | 0.07 mgP/dL |
Phosphorus recoveries of 95 mixed serum and plasma specimens and 44 urine specimens are compared between the HiChem manual procedure and the BMD® Phosphorus Reagent on the Hitachi® 704. Least squares regression statistics are shown below.
Serum/ Plasma Comparisons: (HiChem Results) = -0.1 mgP/dL + 0.982 × (BMD® Results), sy.x = 0.14 mgP/dL r2 = 0.985. Urine Comparisons: sv.x = 0.11 mgP/dL (HiChem Results) = 0.2 mgP/dL + 0.966 x (BMD® Results), r2 = 0.999.
The use of sodium, lithium and ammonium heparin are shown to be acceptable chemical additives by comparison of spiked and unspiked serum pools. In all cases, the biases produced by the additive were less than 0.1 mgP/dL.
510(k) Notification, HiChem Phosphorus Reagent Kit, p 95
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The sensitivity claim of 0.1 mgP/dL is documented through the repetitive assay of a diluted serum control. The observed sensitivity limit, calculated as three standard deviations of a 30 replicate within run precision study, is 0.05 mgP/dL and less than the claim of 0.1 mgP/dL.
The effectiveness of the HiChem secondary reagent application for the Beckman® SYNCHRON CX® Systems is shown by the recovery of linearity standards, the precision of control recovery of serum controls over both the calibration stability and on-board stability claims, the validation of the chemical additives and the comparison of patient specimen recoveries to the Beckman® SYNCHRON® Systems Phosphorus Reagent.
The recovery of inorganic phosphorus using the HiChem PO4 Reagent in the SYNCHRON CX® Systems is linear from at least 1.0 mgP/dL to 12.0 mgP/dL as shown by the recovery of six linearity standards which span the claimed linear range. Regression statistics are shown below.
sy.x = 0.08 mgP/dL, df = 35 (HiChem Recoveries) = -0.2 mgP/dL + 0.971 × (Standard Conc.), r2 = 1.000,
Precision, demonstrated by replicate assay of urine pools and commercially available control sera, is shown below.
| Specimen | n | mean | within-run SD | total SD |
|---|---|---|---|---|
| Serum control 1 | 60 | 1.89 mgP/dL/L | 0.08 mgP/dL | 0.09 mgP/dL |
| Serum control 2 | 60 | 4.13 mgP/dL/L | 0.11 mgP/dL | 0.11 mgP/dL |
| Serum control 3 | 60 | 6.44 mgP/dL/L | 0.10 mgP/dL | 0.10 mgP/dL |
| Urine Pool 1 | 60 | 2.75 mgP/dL/L | 0.11 mgP/dL | 0.11 mgP/dL |
| Urine Pool 2 | 60 | 9.46 mgP/dL/L | 0.08 mgP/dL | 0.13 mgP/dL |
Phosphorus recoveries of 153 mixed serum and plasma specimens are compared between the HiChem and Beckman® PO4 Reagents on the SYNCHRON CX® Systems. Least squares regression statistics are shown below.
Serum/ Plasma Comparisons:
r2 = 0.972, (HiChem Results) = - 0.4 mgP/dL + 1.040 x (BMD® Results), sv.x = 0.15 mgP/dL Urine Comparisons: (HiChem Results) = - 0.2 mgP/dL + 1.001 x (BMD® Results), r2 = 0.996, sv.x = 0.15 mgP/dL
The use of sodium, lithium and ammonium heparin are shown to be acceptable chemical additives by comparison of spiked and unspiked serum pools. In all cases, the observed biases were less than 0.15 mgP/dL.
The sensitivity claim of 1.0 mgP/dL is documented through the repetitive assay of a diluted serum control. The observed sensitivity limit, calculated as three standard deviations of a 30 replicate within run precision study, is 0.3 mgP/dL and is well below the claimed limit of 0.1 mgP/dL.
The 14 day onboard calibration stability, the 60 day within lot callbration stability and the 30 day on board reagent stability claims are documented through the assay of serum controls and urine pools over the claimed periods. In all cases, estimates of imprecision of phosphorus recoveries over the claimed intervals are less than the greater of 0.3 mgP/dL or 3.%, which is the manufacturer's total precision claim for the SYNCHRON® Analyzer.
The HiChem Phosphorus Reagent is shown to be safe and effective and substantially equivalent to the BMD® Phosphorus Reagent, product no. 857427, manufactured by Boehringer Mannheim Corp., Indianapolis, IN., and the Beckman® SYNCHRON® Systems PO4 Reagent, product no. 465145, manufactured by Beckman® Instruments, Brea, CA.
Wynn Storkey
Stocking Manager of Regulatory Affairs HiChem Diagnostics
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN 29 1998
Wynn Stocking . Manager, Regulatory Affairs HiChem Diagnostics 231 North Puente Street 92821 Brea, California
K981769 Re : HiChem Phosphorus Reagent Requlatory Class: I Product Code: CEO Dated: May 18, 1998 Received: May 19, 1998
Dear Mr. Stocking:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਉ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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This letter will allow you to begin marketing your device as Inis lected will arrow you on researce notification. The FDA described in your 510(K) prematics of your device to a legally marketed predicate device results in a classification for your marketed predicate device to proceed to the market. device and thus, permice your device for your device on our labeling of If you desire specific advice for your additionally 809.10 for in vitro diagnostic devices), please contact the Office of Villo diagnoseic acriose/788. Additionally, for questions on Compilance ac (501) 331 issim of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to
premarket notification" (21 CFR 807.97) . Other general information on your responsibilities under the Act may be Information on Joanivision of Small Manufacturers Assistance obcarned from the number (800) 638-2041 or (301) 443-6597 or at its internet address "dsmo@fdadr.cdrh.fda.gov".
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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K981769/A
Page 1 of 1
510(k) Number (if known): K981769
Device Name:
HiChem Phosphorus Reagent Kit
Indications For Use:
HiChem Phosphorus Reagent is intended for the quantitative determination of inorganic phosphorus in serum, plasma and urine for the diagnosis and treatment of various disorders including parathyroid gland and kidney diseases, and vitamin D imbalance.
This reagent is intended to be used in a professional setting or by trained personnel and is not intended for home use.
Respectfully,
Wynn Stocking
Wynh Stocking Regulatory Affairs Manager HiChem Diagnostics
2 June, 1998
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8K-6
§ 862.1580 Phosphorus (inorganic) test system.
(a)
Identification. A phosphorus (inorganic) test system is a device intended to measure inorganic phosphorus in serum, plasma, and urine. Measurements of phosphorus (inorganic) are used in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases, and vitamin D imbalance.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.