K Number
K992842
Date Cleared
1999-11-26

(94 days)

Product Code
Regulation Number
862.1665
Reference & Predicate Devices
N/A
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

HiChem® ISE Electrolyte Reference, when used in conjunction with the HiChem® ISE Electrolyte Buffer, HiChem® CO2 Acid Reagent, HiChem® CO2 Alkaline Buffer, HiChem® Wash Concentrate, and HiChem® Calibration Standards, is intended for the quantitative determination of sodium, chloride, and total CO2 in serum and plasma, and sodium, potassium and chloride in urine, and chloride in cerebrospinal fluid on the Beckman® CX® and CX® DELTA Systems. On appropriately configured SYNCHRON® CX® DELTA Systems, HiChem® ISE Electrolyte Reference will also determine calcium in serum, plasma and urine.

Sodium results are for the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insigidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiurelic hormone secretion, or other diseases involving electrolyte balance. Potassium results are used to monitor electrolyte imbalance in the diagnosis and treatment of diseases and conditions characterized by low or high blood potassium levels. Chloride results are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis. Carbon dioxide results are used in the diagnosis and treatment of numerous and potentially senous disorders associated with changes in the body's acid-base balance. Calcium results are used in the diagnosis and treatment of parathyroid diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

This reagent is intended for professional use only.

Device Description

Not Found

AI/ML Overview

The provided document describes the safety and effectiveness information for the HiChem® ISE Electrolyte Reference kit. The study compares the performance of the HiChem® kit to a predicate device, the SYNCHRON® CX® Systems ISE Electrolyte Reference Kit, manufactured by Beckman Coulter, Inc.

Here's an analysis of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a numerical or categorical format with pass/fail thresholds. Instead, it demonstrates performance by showing the precision and patient comparison results of the HiChem® reagents alongside the predicate Beckman® reagents. The implicit acceptance criterion is that the HiChem® reagents perform comparably to the legally marketed predicate device.

Precision Statistics (HiChem® Reagents vs. Beckman® Reagents)

AnalyteSampleHiChem® Within Run %CV (Max)HiChem® Total %CV (Max)Beckman® Within Run %CV (Max)Beckman® Total %CV (Max)
Calcium in mg/dLSerum 12.1%1.9%2.0%2.0%
Serum 20.8%1.0%0.8%1.1%
Serum 30.9%1.1%0.7%1.1%
Urine 13.5%3.9%3.5%4.2%
Urine 23.1%2.8%2.9%2.8%
Chloride in mmol/LSerum 11.4%1.4%1.0%1.5%
Serum 20.6%1.0%0.7%1.0%
Serum 30.8%1.1%0.6%0.8%
Urine 11.8%1.9%2.0%1.9%
Urine 21.0%2.4%1.1%2.2%
CSF 11.2%1.4%1.3%1.5%
CSF 21.0%1.5%1.4%1.5%
Potassium in meq/LSerum 10.8%1.3%0.8%1.4%
Serum 20.6%0.8%0.7%0.8%
Serum 30.9%1.1%0.7%0.8%
Urine 10.9%1.0%1.1%1.2%
Urine 21.4%1.4%1.8%1.7%
Sodium in meq/LSerum 11.5%1.3%1.5%1.5%
Serum 20.6%0.7%0.7%0.8%
Serum 30.9%0.9%0.6%0.8%
Urine 14.4%3.9%5.5%4.7%
Urine 21.4%1.2%1.7%1.5%
Total CO2 in mmol/LSerum 13.2%3.0%3.0%2.9%
Serum 21.4%1.6%1.5%1.7%
Serum 31.7%2.1%1.2%1.5%

Patient Comparison (Linear Regression of HiChem® vs. Beckman® Results)

AnalyteSpecimenUnitna (Intercept)b (Slope)r (Correlation)
CalciumSerum/Plasmamg/dL1600.00.9890.985
Urinemg/dL74-0.21.0070.998
ChlorideSerum/Plasmammol/L1601.00.9880.935
Urinemmol/L78-5.11.0490.999
CSFmmol/L44-3.41.0240.985
PotassiumSerum/Plasmameq/L1600.130.9691.000
Urinemeq/L800.010.9931.000
SodiumSerum/Plasmameq/L1609.10.9300.938
Urinemeq/L78-0.31.0001.000
Total CO2Serum/Plasmammol/L1601.20.9490.953

The implicit acceptance criteria for this type of submission (510(k)) is substantial equivalence. This means the device must perform as safely and effectively as a legally marketed predicate device. The tables above demonstrate this by showing very similar precision and correlation values between the HiChem® device and the Beckman® predicate device across all analytes and sample types.

2. Sample sizes used for the test set and the data provenance

  • Precision Test Set Sample Sizes:
    • For calcium, chloride, potassium, sodium, and total CO2 across serum, CSF controls, and urine pools:
      • n values varied slightly, mostly around n=60 for each sample type and analyte combination. The exact n values are listed in the precision tables (e.g., Serum 1 for Calcium has n=60 for both HiChem® and Beckman®).
  • Patient Comparison Test Set Sample Sizes:
    • Calcium (Serum/Plasma): 160; Calcium (Urine): 74
    • Chloride (Serum/Plasma): 160; Chloride (Urine): 78; Chloride (CSF): 44
    • Potassium (Serum/Plasma): 160; Potassium (Urine): 80
    • Sodium (Serum/Plasma): 160; Sodium (Urine): 78
    • Total CO2 (Serum/Plasma): 160
  • Data Provenance: The document states "Serum and CSF controls, and urine pools were each assayed..." for precision. For patient comparison, "Serum, plasma, cerebrospinal fluid and urine specimens, collected from adult patients, were assayed..."
    • Country of Origin: Not specified in the provided text.
    • Retrospective or Prospective: Not explicitly stated as retrospective or prospective. However, tests of method comparison for 510(k) are typically prospective or newly acquired samples. The "collected from adult patients" suggests freshly collected samples for the patient comparison study.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This study is for an In Vitro Diagnostic (IVD) device that measures analyte concentrations. The "ground truth" for such devices is typically established through a reference method or by comparing the test device's results with a well-established, legally marketed predicate device (as is the case here).

  • Number of Experts: Not applicable in the context of human expert review for image interpretation or diagnosis. The "ground truth" is the measurement obtained from the predicate device (Beckman® SYNCHRON® CX® DELTA Systems).
  • Qualifications of Experts: Not applicable.

4. Adjudication method for the test set

Not applicable. This is not an imaging or diagnostic device that requires human adjudication of interpretations. The comparison is between quantitative measurements from two different reagent sets on the same analyzer system.

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 is not a study involving human readers or AI assistance. It is a comparison of in vitro diagnostic reagents.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Not applicable in the sense of an algorithm. This is a standalone performance study of the HiChem® reagent kit (without "human-in-the-loop" in the algorithm sense, but human operation of the analyzer is inherent). The study evaluates the performance of the HiChem® reagents directly against the predicate Beckman® reagents.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" in this context is the results obtained from the predicate device (SYNCHRON® CX® Systems ISE Electrolyte Reference Kit manufactured by Beckman Coulter, Inc.) running on the specified Beckman® SYNCHRON® CX® and CX® DELTA Systems. The goal is to show the HiChem® kit yields results substantially equivalent to the established predicate.

8. The sample size for the training set

Not applicable. This represents a traditional IVD device submission, not a machine learning/AI device that typically involves distinct training and test sets. The data presented are for performance validation (equivalent to a test set in ML terms, but focused on demonstrating equivalence).

9. How the ground truth for the training set was established

Not applicable, as there is no training set in this context.

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NOV 26 1999

Image /page/0/Picture/1 description: The image is a logo for "élan". The logo features a stylized letter "e" formed by several parallel lines, with a wing-like shape extending from the left side of the "e". Below the symbol is the word "élan" in a sans-serif font, with an acute accent over the "e". The logo is black and white.

élan diagnostics

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® ISE Electrolyte Reference is intended for the quantitative determination of sodium, chloride, and total CO2 in serum and plasma, and sodium and chloride in urine, and chloride in cerebrospinal fluid on the Beckman® SYNCHRON® CX® and CX® DELTA Systems. On appropriately configured SYNCHRON® CX® DELTA Systems, HiChem® ISE Electrolyte Reference will also determine calcium in serum, plasma and urine.

The HiChem® ISE Electrolyte Reference Kit is substantially equivalent to the SYNCHRON® CX® Systems ISE Electrolyte Reference Kit, product no. 450214, manufactured by Beckman Coulter, Inc.

The effectiveness of the ISE Electrolyte Reference Kit is shown by the following studies.

Precision

Serum and CSF controls, and urine pools were each assayed for calcium, chloride, potassium, and total CO2 twice per day in triplicate on a SYNCHRON® CX® DELTA System using both HiChem® and Beckman® flow cell reagents, wash solutions and calibrators. Data were collected on ten different days over a thirty day period. Estimates of within run and total imprecision were calculated as described in NCCLS publication EP3-T.

Precision Statistics

AnalyteSamplenHiChem® ReagentsWithin RunTotalnBeckman® ReagentsWithin RunTotal
mean1SD%CV1SD%CVmean1SD%CV1SD%CV
Calcium in mg/dL
Serum 1607.90.162.1%0.151.9%607.90.162.0%0.152.0%
Serum 26011.10.090.8%0.111.0%6011.20.090.8%0.121.1%
Serum 36014.20.130.9%0.161.1%6014.40.100.7%0.161.1%
Urine 1593.40.123.5%0.133.9%603.50.123.5%0.144.2%
Urine 26010.90.333.1%0.302.8%6011.10.332.9%0.312.8%
Chloride in mmol/L
Serum 16084.51.161.4%1.211.4%6084.60.861.0%1.271.5%
Serum 260103.20.600.6%1.041.0%60103.40.740.7%1.011.0%
Serum 360122.61.010.8%1.341.1%60122.20.770.6%1.000.8%
Urine 15964.11.161.8%1.211.9%6064.11.282.0%1.241.9%
Urine 260235.62.331.0%5.672.4%60229.62.611.1%5.072.2%
CSF 158117.51.371.2%1.651.4%59117.31.571.3%1.731.5%
CSF 25899.11.001.0%1.451.5%5899.21.371.4%1.501.5%
Potassium in meq/L
Serum 1602.640.0210.8%0.0341.3%602.590.0190.8%0.0351.4%
Serum 2605.210.0310.6%0.0400.8%605.220.0370.7%0.0430.8%
Serum 3607.880.0740.9%0.0831.1%607.930.0570.7%0.0650.8%
Urine 15927.10.230.9%0.271.0%6027.30.311.1%0.321.2%
Urine 260123.71.671.4%1.671.4%60124.52.221.8%2.101.7%

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K992842

Precision Statistics (continued)

AnalyteSampleHiChem® ReagentsBeckman® Reagents
nmean1SD%CV1SD%CVnmean1SD%CV1SD%CV
Sodium in meq/LSerum 160114.71.711.5%1.511.3%60114.91.721.5%1.691.5%
Serum 260144.40.870.6%0.940.7%60144.90.970.7%1.220.8%
Serum 360173.31.540.9%1.590.9%60174.01.080.6%1.310.8%
Urine 15945.72.024.4%1.783.9%6045.82.515.5%2.154.7%
Urine 260159.92.191.4%1.981.2%60160.42.671.7%2.391.5%
Total CO2 in mmol/LSerum 16012.60.403.2%0.383.0%6012.70.383.0%0.362.9%
Serum 26022.20.321.4%0.361.6%6022.30.331.5%0.371.7%
Serum 36030.90.531.7%0.662.1%6031.10.361.2%0.481.5%

Patient Comparison

Serum, plasma, cerebrospinal fluid and urine specimens, collected from adult patients, were assayed for calcium, chloride, potassium, sodium, and total CO2 on a SYNCHRON® CX® DELTA System using HiChem® and Beckman® low cell reagents, wash solutions and calibrators. Results were compared by least squares linear regression where X = Beckman® Results and Y = HiChem® Results.

AnalyteSpecimenUnitnabrrangemean Xmean Y
CalciumSerum/Plasmamg/dL1600.00.9890.9857.1 - 10.69.269.13
Urinemg/dL74-0.21.0070.9982.4 - 15.28.458.3
ChlorideSerum/Plasmammol/L1601.00.9880.93598.2 - 127.5107.3107.0
Urinemmol/L78-5.11.0490.99922.4 - 289126.8127.9
CSFmmol/L44-3.41.0240.985113.8 - 152.4126.5126.1
PotassiumSerum/Plasmameq/L1600.130.9691.0003.20 - 10.825.025.00
Urinemeq/L800.010.9931.0003.48 - 136.050.550.2
SodiumSerum/Plasmameq/L1609.10.9300.938131.8 - 159.1141.0140.3
Urinemeq/L78-0.31.0001.00016.9 - 288.1118.2117.8
Total CO2Serum/Plasmammol/L1601.20.9490.9539.5 - 29.123.323.2

Wynn Stocking
Wynn Stocking

Manager of Regulatory Affairs Elan Diagnostics

20 August, 1999

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the top half of the circle. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 26 1999

Mr. Wynn Stocking Manager, Regulatory Affairs Elan Diagnostics 231 N. Puente Street Brea, California 92821

Re: K992842

Trade Name: HiChem® ISE Electrolyte Reference Regulatory Class: II Product Code: JGS, CEM, CGZ, JFL, JFP Dated: November 10, 1999 Received: November 12, 1999

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 legally marketed predicate 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 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 regulations affecting your device can be found in the Code of Federal Regulations, 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 action. In addition, FDA may publish further announcements 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.

{3}------------------------------------------------

Page 2

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/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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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K992842 510(k) Number (if known):

HiChem® ISE Electrolyte Reference Device Name:

Indications For Use:

HiChem® ISE Electrolyte Reference, when used in conjunction with the HiChem® ISE Electrolyte Buffer, HiChem® CO2 Acid Reagent, HiChem® CO2 Alkaline Buffer, HiChem® Wash Concentrate, and HiChem® Calibration Standards, is intended for the quantitative determination of sodium, chloride, and total CO2 in serum and plasma, and sodium, potassium and chloride in urine, and chloride in cerebrospinal fluid on the Beckman® CX® and CX® DELTA Systems. On appropriately configured SYNCHRON® CX® DELTA Systems, HiChem® ISE Electrolyte Reference will also determine calcium in serum, plasma and urine.

Sodium results are for the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insigidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiurelic hormone secretion, or other diseases involving electrolyte balance. Potassium results are used to monitor electrolyte imbalance in the diagnosis and treatment of diseases and conditions characterized by low or high blood potassium levels. Chloride results are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis. Carbon dioxide results are used in the diagnosis and treatment of numerous and potentially senous disorders associated with changes in the body's acid-base balance. Calcium results are used in the diagnosis and treatment of parathyroid diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

This reagent is intended for professional use only.

Respectfully,

Wynn Stocking Requiatory Affairs Manager Elan Diagnostics

10 November, 1999

Dean Cooper

Division of Clinical Laboratory Devices
510(k) Number K992842

(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)

OR

Over-The-Counter Use __

(Optional Format 1-2-96)

§ 862.1665 Sodium test system.

(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.