HICHEM CALCIUM REAGENT KIT by HICHEM DIAGNOSTICS

HiChem Calcium Reagent is intended for the quantitative determination of total calcium in serum, plasma and urine. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Device Description

The HiChem Calcium Reagent determines calcium by its reaction with arsenazo III to form a blue complex. The resulting increase in absorbance at 650 nm is proportional to the calcium concentration in the sample. The HiChern Calcium Reagent is an adaptation of the arsenazo III calcium method, first reported by Michaylova and Illikova and is intended to be used either as a manual procedure or on clinical analyzers which can automate the required manipulations.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the HiChem Calcium Reagent, based on the provided text:

Acceptance Criteria and Device Performance

The provided text describes two main scenarios for the HiChem Calcium Reagent: the manual procedure and its use on the Beckman® SYNCHRON CX® Systems (secondary reagent application). The acceptance criteria are largely implied by the reported performance, as the study aims to demonstrate substantial equivalence to an existing predicate device.

Table of Acceptance Criteria and Reported Device Performance

Performance Measure	Acceptance Criteria (Implied)	HiChem Calcium Reagent (Manual Procedure) Reported Performance	HiChem Calcium Reagent (SYNCHRON CX® Systems) Reported Performance
Linearity	Demonstrate linearity over a specific range.	Linear between 0.1 to 16 mg/dL. Regression: (HiChem) = -0.1 + 0.980 x (Standard Conc.), r² = 1.000, sy.x = 0.14 mg/dL.	Linear from at least 2.0 mg/dL to 15.0 mg/dL. Regression: (HiChem) = 0.0 + 0.967 x (Standard Conc.), r² = 1.000, sy.x = 0.08 mg/dL.
Precision	Meet specified SD for various control levels.	Serum Control 1 (6.69 mg/dL): within-run SD 0.21 mg/dL, total SD 0.24 mg/dL Serum Control 2 (12.68 mg/dL): within-run SD 0.29 mg/dL, total SD 0.30 mg/dL Urine Pool 1 (2.41 mg/dL): within-run SD 0.11 mg/dL, total SD 0.11 mg/dL Urine Pool 2 (11.10 mg/dL): within-run SD 0.13 mg/dL, total SD 0.16 mg/dL	Serum Control 1 (6.89 mg/dL): within-run SD 0.056 mg/dL, total SD 0.064 mg/dL Serum Control 2 (10.03 mg/dL): within-run SD 0.085 mg/dL, total SD 0.089 mg/dL Serum Control 3 (13.21 mg/dL): within-run SD 0.088 mg/dL, total SD 0.090 mg/dL Urine Pool 1 (3.24 mg/dL): within-run SD 0.048 mg/dL, total SD 0.059 mg/dL Urine Pool 2 (11.64 mg/dL): within-run SD 0.075 mg/dL, total SD 0.095 mg/dL
Method Comparison (Serum/Plasma)	Substantial equivalence to Beckman® SYNCHRON® Calcium Reagent.	n=92. Regression: (HiChem) = -0.3 + 1.020 × (BMD® Results), r² = 0.887, s(y.x) = 0.21 mg/dL.	n=153. Regression: (HiChem) = -0.3 + 1.005 x (Beckman® Results), r² = 0.924, s(y.x) = 0.20 mg/dL.
Method Comparison (Urine)	Substantial equivalence to Beckman® SYNCHRON® Calcium Reagent.	Regression: (HiChem) = 0.2 + 1.022 × (BMD® Results), r² = 0.998, s(y.x) = 0.15 mg/dL.	Regression: (HiChem) = 0.1 + 1.031 x (Beckman® Results), r² = 0.996, s(y.x) = 0.16 mg/dL.
Chemical Additives (Interference)	Biases less than a specified threshold (e.g., < 0.1-0.2 mg/dL).	Biases less than 0.1 mg/dL for sodium heparin, lithium heparin, lithium iodoacetate.	Biases less than 0.2 mg/dL for sodium heparin, lithium heparin, lithium iodoacetate.
Sensitivity	Achieves claimed sensitivity (e.g., 0.2 mg/dL).	Claimed: 0.2 mg/dL. Observed sensitivity limit: 0.15 mg/dL (based on 3 SD of 30 replicate study).	Claimed: 2.0 mg/dL. Observed sensitivity limit: < 0.15 mg/dL (based on 3 SD of 30 replicate within-run precision study).
Calibration Stability (SYNCHRON CX®)	Imprecision < 0.26 mg/dL or 2.6% (Beckman's claim).	Not applicable to manual procedure.	14 days, imprecision < 0.26 mg/dL or 2.6%.
Onboard Reagent Stability (SYNCHRON CX®)	Imprecision < 0.26 mg/dL or 2.6% (Beckman's claim).	Not applicable to manual procedure.	30 days, imprecision < 0.26 mg/dL or 2.6%.

Study Details

The studies described are primarily designed to demonstrate substantial equivalence to the predicate device, the Beckman® Systems Calcium Reagent. This means the new device performs similarly enough to the legally marketed device that it is considered safe and effective for the same intended use.

Sample Size used for the test set and the data provenance:
- Manual Procedure:
  - Linearity: 23 data points (df) for linearity standards spanning 0-18 mg/dL.
  - Precision: 30 replicates (n) for each of 4 control specimens (2 serum, 2 urine).
  - Method Comparison: 92 mixed serum and plasma specimens.
  - Sensitivity: 30 replicates for a diluted serum control.
- SYNCHRON CX® Systems Application:
  - Linearity: 29 data points (df) for six linearity standards spanning "at least 2.0 mg/dL to 15.0 mg/dL."
  - Precision: 60 replicates (n) for each of 5 control specimens (3 serum, 2 urine).
  - Method Comparison: 153 mixed serum and plasma specimens.
  - Sensitivity: 30 replicates for a diluted serum control.
- Data Provenance: Not explicitly stated but implied to be laboratory-generated data for performance characteristics and potentially patient samples for method comparisons. No specific country of origin is mentioned, nor is it explicitly stated as retrospective or prospective, though the nature of laboratory validation studies often implies prospective data collection for the specific tests performed.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This type of study for a laboratory reagent does not typically involve human experts establishing ground truth in the same way as, for example, an imaging AI study. The "ground truth" for these tests comes from:
  - Assigned values of linearity standards: These are precisely manufactured solutions with known calcium concentrations.
  - Assigned values of control sera/urine: These are commercially available reference materials with established target values.
  - Results from the predicate device (Beckman® SYNCHRON® Calcium Reagent): For method comparison studies, the predicate device's results serve as the reference standard against which the new device is compared.
- Therefore, no information on "number of experts" or their "qualifications" is provided or relevant in this context.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This is a quantitative reagent study, not an imaging or qualitative diagnostic study requiring expert adjudication of results. The results are numerical measurements.
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 is a study of a laboratory reagent's performance in quantitative measurement, not an AI-assisted diagnostic tool involving human readers.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance data presented (linearity, precision, method comparison, sensitivity, stability) for both the manual procedure and the automated SYNCHRON CX® Systems application represent the standalone performance of the HiChem Calcium Reagent. While a human initiates the tests and interprets the results, the data itself reflects the reagent's analytical capability. There is no "human-in-the-loop" interaction in the sense of an AI interpreting images for a human.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- Reference Method/Comparator: The primary "ground truth" for comparison is the Beckman® SYNCHRON® Calcium Reagent, which is the legally marketed predicate device. The study aims to show that the HiChem reagent produces results substantially equivalent to this established method.
- Known Reference Values: For linearity and precision studies, the ground truth is based on known, pre-assigned concentrations in linearity standards and commercial control materials. These values are derived through rigorous analytical methods by the manufacturers of these standards/controls.
The sample size for the training set:
- Not applicable. This is a chemical reagent, not a machine learning algorithm that requires a "training set" in the computational sense. The "development" or "formulation" of the reagent would involve extensive R&D and optimization, but it's not parallel to training a neural network on a dataset.
How the ground truth for the training set was established:
- Not applicable for the reason stated above.

Summary

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JUL 20 1998

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9817-94

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.

The HiChern Calcium Reagent is an adaptation of the arsenazo III calcium method, first reported by Michaylova and Illikova and is intended to be used either as a manual procedure or on clinical analyzers which can automate the required manipulations.

The HiChern Calcium Reagent is substantially equivalent to the Beckman® Systems Calcium Reagent, product no. 442755, manufactured by Beckman® Instruments, Brea, CA. Both reagents support the same intended use and produce substantially equivalent results with the same clinical purpose. In addition, they are methodology which determines total calcium through the colorimetric measurement the calcium - arsenazo III complex.

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 Beckman® Calcium Reagent and the validation of the chemical additives and sensitivity claims.

The recovery of total calcium using HiChem Calcium Reagent as a manual procedure is linear between 0.1 to 16 mg/dL as shown by the recovery of linearity standards which span 0 to 18 mg/dL. Regression statistics are shown below.

sy.x = 0.14 mg/dL., (HiChem Recoveries) = - 0.1 mg/dL + 0.980 x (Standard Conc.), r2 = 1.000, 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	6.69 mg/dL	0.21 mg/dL	0.24 mg/dL
Serum control 2	30	12.68 mg/dL	0.29 mg/dL	0.30 mg/dL
Urine Pool 1	30	2.41 mg/dL	0.11 mg/dL	0.11 mg/dL
Urine Pool 2	30	11.10 mg/dL	0.13 mg/dL	0.16 mg/dL

Calcium recoveries of 92 mixed serum and plasma specimens are compared between the HiChem manual procedure and the Beckman® SYNCHRON® Calcium Reagent, used on the SYNCHRON CX® Systems. Least squares regression statistics are shown below.

Serum/ Plasma Comparisons:
(HiChem Results) = -0.3 mg/dL + 1.020 × (BMD® Results)	r² = 0.887	s(y.x) = 0.21 mg/dL
Urine Comparisons:
(HiChem Results) = 0.2 mg/dL + 1.022 × (BMD® Results)	r² = 0.998	s(y.x) = 0.15 mg/dL

The use of sodium heparin, lithium heparin and lithium iodoacetate are shown to be acceptable chemical additives by comparison of spiked serum pools. In all cases, the biases produced by the additive were less than 0.1 mg/dL.

The sensitivity claim of 0.2 mg/dL is documented through the repettive assay of a diluted serum control. The observed sensitivity limit, calculated as three standard deviations of a 30 recision study, is 0.15 mg/dl. and is below the claimed limit of 0.2 mg/dL.

510(k) Notification, HiChem Calcium Reagent Kit, p 61

20 May, 1998

2024 Native Student Orientation Schedule: August 18, 2024

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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 sensitivity claims, and the comparison of patient specimen recoveries to the Beckman® SYNCHRON® Systems Calcium Reagent.

The recovery of total calcium using the HiChem CA Reagent on the SYNCHRON CX® Systems is linear from at least 2.0 mg/dL to 15.0 mg/dL as shown by the recovery of six linearity standards which span the claimed linear range. Regression statistics are shown below.

(HiChem Recoveries) = 0.0 mg/dL + 0.967 × (Standard Conc.), r2 = 1.000. sy.x = 0.08 mg/dL, df = 29

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	6.89 mg/dL	0.056 mg/dL	0.064 mg/dL
Serum control 2	60	10.03 mg/dL	0.085 mg/dL	0.089 mg/dL
Serum control 3	60	13.21 mg/dL	0.088 mg/dL	0.090 mg/dL
Urine Pool 1	60	3.24 mg/dL	0.048 mg/dL	0.059 mg/dL
Urine Pool 2	60	11.64 mg/dL	0.075 mg/dL	0.095 mg/dL

Calcium recoveries of 153 mixed serum and plasma specimens are compared between the HiChem and Beckman® CA Reagents on the SYNCHRON CX® Systems. Least squares regression statistics are shown below.

Serum/ Plasma Comparisons:

(HiChem Results) = -0.3 mg/dL + 1.005 x (Beckman® Results) $r^2$ = 0.924	s(y.x) = 0.20 mg/dL
Urine Comparisons:
(HiChem Results) = 0.1 mg/dL + 1.031 x (Beckman® Results) $r^2$ = 0.996	s(y.x) = 0.16 mg/dL

The use of sodium heparin, lithium heparin and lithium iodoacetate are shown to be acceptable chemical additives by comparison of spiked serum pools. In all cases, the observed biases were less than 0.2 mg/d..

The sensitivity claim of 2.0 mg/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 less than 0.15 mg/dL and is well below the claimed limit of 2.0 mg/dL.

The 14 day onboard calibration 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 calcium recoveries over the claimed intervals are less than the greater of 0.26 mg/dL or 2.6%, which is the manufacturer's total precision claim for the SYNCHRON® Analyzer.

The HiChem Calcium Reagent is shown to be safe and effective and substantially equivalent to the Beckman® SYNCHRON® Systems Calcium Reagent, product no. 442755, manufactured by Beckman® Instruments, Brea, CA.

Wynne Stocking

Manager of Regulatory Affairs HiChem Diagnostics

510(k) Notification, HiChem Calcium Reagent Kit, p 62

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 2 9 1998

Wynn Stocking . Manager, Regulatory Affairs HiChem Diagnostics 231 North Puente Street Brea, California 92821

K981794 Re : HiChem Calcium Reagent Regulatory Class: II Product Code: CJY Dated: May 20, 1998 Received: May 21, 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, Druq, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions 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 requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A 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 Reqister. 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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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising 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 obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

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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K981794 510(k) Number (if known):

Device Name:

HiChem Calcium Reagent Kit

Indications For Use:

HiChem Calcium Reagent is intended for the quantitative determination of total calcium in serum, Hichent Calcioin Reagent is mended for the qualifical disease, a variety of bone plasma and unne for the the tradinons and telany (intermittent muscular contractions or spasms).

This reagent is intended to be used in a professional setting or by trained personnel and Is not intended for home use.

Respectfully.

Wynn Stordins

Regulatory Affairs Manager HiChem Diagnostics

2 Juno, 1998

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use __
(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1145 Calcium test system.

(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.