HICHEM PHOSPHORUS REAGENT KIT

K981769 · Elan Pharma, Inc. · CEO · Jun 29, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981769
• Device Name: HICHEM PHOSPHORUS REAGENT KIT
• Applicant: Elan Pharma, Inc.
• Product Code: CEO · Clinical Chemistry
• Decision Date: Jun 29, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1580
• Device Class: Class 1

Intended 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.

Device Story

HiChem Phosphorus Reagent is an in vitro diagnostic chemical reagent kit. It utilizes a molybdate-based colorimetric method to measure inorganic phosphorus in serum, plasma, or urine samples. The reagent reacts with phosphorus in an acidic solution to form a phosphomolybdate complex; the resulting increase in absorbance at 340 nm is measured via spectrophotometry. The device is intended for use in clinical laboratories by trained personnel using manual spectrophotometers or automated clinical analyzers (e.g., Hitachi 704, Beckman SYNCHRON CX Systems). Healthcare providers use the resulting phosphorus concentration values to diagnose and monitor metabolic, parathyroid, and renal disorders. The reagent provides a standardized, automated, or manual method for quantitative analysis, facilitating clinical decision-making regarding patient treatment plans.

Clinical Evidence

Bench testing only. Performance validated via linearity studies (0.1–15 mgP/dL manual; 1.0–12.0 mgP/dL automated), precision studies (within-run and total SD), and method comparison studies. Serum/plasma/urine recoveries compared to predicate reagents using least squares regression (r2 values 0.972–0.999). Sensitivity limits documented via repetitive assay of diluted serum controls. Chemical additive interference (heparin) evaluated with bias <0.15 mgP/dL.

Technological Characteristics

Colorimetric reagent kit; molybdate-based chemistry; acidic solution; spectrophotometric detection at 340 nm. Compatible with manual spectrophotometers and automated clinical analyzers (Hitachi 704, Beckman SYNCHRON CX). Reagent stability validated for 30 days on-board; calibration stability validated for 14-60 days. No electronic components; software-independent reagent chemistry.

Indications for Use

Indicated for quantitative determination of inorganic phosphorus in serum, plasma, and urine to aid diagnosis/treatment of parathyroid gland disease, kidney disease, and vitamin D imbalance. For professional use only; not for home use.

Regulatory Classification

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.

Predicate Devices

• BMD Phosphorus Reagent (product no. 857427)
• Beckman SYNCHRON Systems Phosphorus Reagent (product no. 465145)

Submission Summary (Full Text)

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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.

K981769

## 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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Image /page/2/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three bars representing its wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.

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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Page 2

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 [phone]. 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 [phone] or [phone] or at its internet address "[e-mail]".

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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