HiChem® ISE Electrolyte Buffer, when used in conjunction with the HiChem® ISE Electrolyte Reference, 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 Buffer 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 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 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

HiChem® ISE Electrolyte Buffer is intended for the quantitative determination of sodium, potassium, chloride, and total CC2 in serum and plasma, and sodium, potassium 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 Buffer will also determine calcium in serum, plasma and urine.

AI/ML Overview

The provided document describes the safety and effectiveness information for the HiChem® ISE Electrolyte Buffer, which is intended for the quantitative determination of various electrolytes in biological fluids. The study aims to demonstrate substantial equivalence to a predicate device, the SYNCHRON® CX® Systems ISE Electrolyte Buffer Kit.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for "substantial equivalence" are implicitly demonstrated through performance comparable to a legally marketed predicate device. This is evaluated through precision studies (imprecision, expressed as %CV) and patient comparison studies (linear regression analysis, including slope 'b', intercept 'a', and correlation coefficient 'r'). The device is considered to meet acceptance criteria if its performance is comparable to or better than the predicate device across various analytes and sample types.

Precision Study Acceptance Criteria (Implicit for Substantial Equivalence):
The HiChem® Reagents should show similar or better precision (lower %CV) compared to the Beckman® Reagents for all analytes and sample types.

Analyte	Sample	HiChem® Reagents - Total %CV (Reported)	Beckman® Reagents - Total %CV (Predicate)	Acceptance Met? (HiChem ≤ Beckman)
Calcium in mg/dL	Serum 1	1.9%	2.0%	Yes
	Serum 2	1.0%	1.1%	Yes
	Serum 3	1.1%	1.1%	Yes
	Urine 1	3.9%	4.2%	Yes
	Urine 2	2.8%	2.8%	Yes
Chloride in mmol/L	Serum 1	1.4%	1.5%	Yes
	Serum 2	1.0%	1.0%	Yes
	Serum 3	1.1%	0.8%	No (HiChem higher)
	Urine 1	1.9%	1.9%	Yes
	Urine 2	2.4%	2.2%	No (HiChem higher)
	CSF 1	1.4%	1.5%	Yes
	CSF 2	1.5%	1.5%	Yes
Potassium in meq/L	Serum 1	1.3%	1.4%	Yes
	Serum 2	0.8%	0.8%	Yes
	Serum 3	1.1%	0.8%	No (HiChem higher)
	Urine 1	1.0%	1.2%	Yes
	Urine 2	1.4%	1.7%	Yes
Sodium in meq/L	Serum 1	1.3%	1.5%	Yes
	Serum 2	0.7%	0.8%	Yes
	Serum 3	0.9%	0.8%	No (HiChem higher)
	Urine 1	3.9%	4.7%	Yes
	Urine 2	1.2%	1.5%	Yes
Total CO2 in mmol/L	Serum 1	3.0%	2.9%	No (HiChem higher)
	Serum 2	1.6%	1.7%	Yes
	Serum 3	2.1%	1.5%	No (HiChem higher)

Patient Comparison Study Acceptance Criteria (Implicit for Substantial Equivalence):
The linear regression parameters (slope 'b', intercept 'a', and correlation coefficient 'r') for HiChem® vs. Beckman® results should ideally be close to b=1, a=0, and r=1, indicating close agreement between the two reagent systems. There are no explicit numerical thresholds stated, but typical acceptance ranges for such studies would be, for example, a slope between 0.95 and 1.05 and a correlation coefficient (r) above 0.975 (or 0.98), though these are not formally defined in the document.

Analyte	Specimen	Unit	n	Slope 'b' (Reported)	Intercept 'a' (Reported)	Correlation 'r' (Reported)	Acceptance Met? (Implicit: b near 1, a near 0, r near 1)
Calcium	Serum/Plasma	mg/dL	160	0.989	0.0	0.985	Yes (appears good)
	Urine	mg/dL	74	1.007	-0.2	0.998	Yes (appears very good)
Chloride	Serum/Plasma	mmol/L	160	0.988	1.0	0.935	Moderately good correlation, intercept slightly high.
	Urine	mmol/L	78	1.049	-5.1	0.999	Very good correlation, but intercept is somewhat large.
	CSF	mmol/L	44	1.024	-3.4	0.985	Good correlation, but intercept is somewhat large.
Potassium	Serum/Plasma	meq/L	160	0.969	0.13	1.000	Very good (perfect correlation reported).
	Urine	meq/L	80	0.993	0.01	1.000	Very good (perfect correlation reported).
Sodium	Serum/Plasma	meq/L	160	0.930	9.1	0.938	Lower correlation and larger intercept.
	Urine	meq/L	78	1.000	-0.3	1.000	Very good (perfect correlation reported).
Total CO2	Serum/Plasma	mmol/L	160	0.949	1.2	0.953	Good, but slightly lower correlation and higher intercept.

Summary of Acceptance: While there are a few instances where the HiChem® Reagents show slightly higher %CV in the precision study, these differences are generally small. The patient comparison study generally shows good agreement (high 'r' values and 'b' values close to 1), although some intercepts ('a') are noticeable, and the correlation for Chloride and Sodium in Serum/Plasma is somewhat lower than other analytes. Overall, the provided data aims to demonstrate "substantial equivalence", and the FDA's clearance (K992844) indicates that these results were considered acceptable.

2. Sample Size Used for the Test Set and the Data Provenance

Precision Study Test Set:
- For calcium, chloride, potassium, sodium, and total CO2, 60 replicates (n=60) were performed for most serum and urine samples with HiChem reagents, and 59 or 58 for some CSF and urine samples. The same applies to Beckman reagents.
- Data collection occurred twice per day in triplicate over ten different days (totaling 30 days time frame).
- Data Provenance: Not explicitly stated, but the study was conducted using the Beckman® SYNCHRON® CX® DELTA System. It is likely that the controls and pools used were standard laboratory materials, not patient samples specifically.
Patient Comparison Study Test Set:
- Calcium: Serum/Plasma (n=160), Urine (n=74)
- Chloride: Serum/Plasma (n=160), Urine (n=78), CSF (n=44)
- Potassium: Serum/Plasma (n=160), Urine (n=80)
- Sodium: Serum/Plasma (n=160), Urine (n=78)
- Total CO2: Serum/Plasma (n=160)
- Data Provenance: "Serum, plasma, cerebrospinal fluid and urine specimens, collected from adult patients" were used. The country of origin for these patients is not specified, but it's implied to be retrospective as they are "collected specimens."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

This document describes the performance of a diagnostic reagent kit, not a device requiring human interpretation of results. The "ground truth" for the precision study would be the true concentration of the analytes in the controlled samples (controls, urine pools). For the patient comparison study, the "ground truth" for evaluating the HiChem® device's performance is the results obtained from the predicate Beckman® reagent system. No human experts are used for establishing ground truth in this type of in vitro diagnostic device study; the "ground truth" is established by the reference method (the predicate device) or by the known concentrations of quality control materials.

4. Adjudication Method for the Test Set

Not applicable. This is an in vitro diagnostic (IVD) device measuring quantitative analytes. Results are numerical and compared directly to a predicate device's numerical results or to known concentrations for quality control. There is no human interpretation or adjudication involved in determining the "truth."

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

No, an MRMC study was not done. This type of study is relevant for imaging devices or other diagnostics where human readers interpret results, often with and without AI assistance, to assess the impact of the AI on diagnostic accuracy or efficiency. This document concerns an in vitro diagnostic reagent kit, which does not involve human readers in the interpretation of raw data.

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

Yes, implicitly. The performance data presented for the HiChem® ISE Electrolyte Buffer is its "standalone" performance when run on the specified Beckman® SYNCHRON® CX® and CX® DELTA Systems. The device itself is a reagent and operates automatically once specimens are introduced to the analyzer. The results are generated directly by the analytical system using the reagent, without human intervention in the result calculation or interpretation beyond operating the instrument and ensuring quality control.

7. The type of ground truth used

Precision Study: The ground truth for evaluating imprecision is the mean concentration of the analyte within the control material or urine pools, and then the variability (SD, %CV) around that mean is calculated. The "true" concentration of these controls/pools serves as a reference.
Patient Comparison Study: The ground truth for evaluating agreement is the results obtained from the predicate device (Beckman® reagents). The HiChem® results are compared against these predicate results via linear regression to demonstrate substantial equivalence, not against an external, independent "gold standard" truth like pathology or patient outcomes.

8. The Sample Size for the Training Set

The document describes a 510(k) submission for a new reagent kit, demonstrating its performance. It does not utilize machine learning or AI that would require a distinct "training set" in the computational sense. The "training" for such a system would typically refer to the internal development and calibration of the reagent and the analytical device itself, which is not detailed here. The studies described (precision, patient comparison) are validation studies.

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

As there is no "training set" in the conventional AI/ML sense for this type of IVD device, this question is not applicable. The device's calibration and performance characteristics would have been established by the manufacturer through rigorous internal development and testing, likely using certified reference materials and established analytical methods.

Summary

{0}------------------------------------------------

V 26 1999

élan diagnostics

K992844

Summary of 510(k) Safetv 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 HiChem® ISE Electrolyte Buffer Kit is substantially equivalent to the SYNCHRON® CX® Systems ISE Electrolyte Buffer Kit, product no. 472095, manufactured by Beckman Coulter, Inc.

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

Precision

Serum and CSF controls, and urine pools were each assayed for calcium, chioride, potassium, sodium, 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

	HiChem® Reagents							Beckman® Reagents
Analyte		Within Run		Total			Within Run		Total
Sample	n	mean	1SD	%CV	1SD	%CV	n	mean	1SD	%CV	1SD	%CV
Calcium in mg/dL
Serum 1	60	7.9	0.16	2.1%	0.15	1.9%	60	7.9	0.16	2.0%	0.15	2.0%
Serum 2	60	11.1	0.09	0.8%	0.11	1.0%	60	11.2	0.09	0.8%	0.12	1.1%
Serum 3	60	14.2	0.13	0.9%	0.16	1.1%	60	14.4	0.10	0.7%	0.16	1.1%
Urine 1	59	3.4	0.12	3.5%	0.13	3.9%	60	3.5	0.12	3.5%	0.14	4.2%
Urine 2	60	10.9	0.33	3.1%	0.30	2.8%	60	11.1	0.33	2.9%	0.31	2.8%
Chloride in mmol/L
Serum 1	60	84.5	1.16	1.4%	1.21	1.4%	60	84.6	0.86	1.0%	1.27	1.5%
Serum 2	60	103.2	0.60	0.6%	1.04	1.0%	60	103.4	0.74	0.7%	1.01	1.0%
Serum 3	60	122.6	1.01	0.8%	1.34	1.1%	60	122.2	0.77	0.6%	1.00	0.8%
Urine 1	59	64.1	1.16	1.8%	1.21	1.9%	60	64.1	1.28	2.0%	1.24	1.9%
Urine 2	60	235.6	2.33	1.0%	5.67	2.4%	60	229.6	2.61	1.1%	5.07	2.2%
CSF 1	58	117.5	1.37	1.2%	1.65	1.4%	59	117.3	1.57	1.3%	1.73	1.5%
CSF 2	58	99.1	1.00	1.0%	1.45	1.5%	58	99.2	1.37	1.4%	1.50	1.5%
Potassium in meq/L
Serum 1	60	2.64	0.021	0.8%	0.034	1.3%	60	2.59	0.019	0.8%	0.035	1.4%
Serum 2	60	5.21	0.031	0.6%	0.040	0.8%	60	5.22	0.037	0.7%	0.043	0.8%
Serum 3	60	7.88	0.074	0.9%	0.083	1.1%	60	7.93	0.057	0.7%	0.065	0.8%
Urine 1	59	27.1	0.23	0.9%	0.27	1.0%	60	27.3	0.31	1.1%	0.32	1.2%
Urine 2	60	123.7	1.67	1.4%	1.67	1.4%	60	124.5	2.22	1.8%	2.10	1.7%

{1}------------------------------------------------

Precision Statistics (continued)

HiChem® Reagents								Beckman® Reagents
Analyte	Sample	n	Within Run		Total			n	Within Run		Total
			mean	1SD	%CV	1SD	%CV			mean	1SD	%CV	1SD	%CV
Sodium in meq/L	Serum 1	60	114.7	1.71	1.5%	1.51	1.3%		60	114.9	1.72	1.5%	1.69	1.5%
	Serum 2	60	144.4	0.87	0.6%	0.94	0.7%		60	144.9	0.97	0.7%	1.22	0.8%
	Serum 3	60	173.3	1.54	0.9%	1.59	0.9%		60	174.0	1.08	0.6%	1.31	0.8%
	Urine 1	59	45.7	2.02	4.4%	1.78	3.9%		59	45.8	2.51	5.5%	2.15	4.7%
	Urine 2	60	159.9	2.19	1.4%	1.98	1.2%		60	160.4	2.67	1.7%	2.39	1.5%
Total CO2 in mmol/L	Serum 1	60	12.6	0.40	3.2%	0.38	3.0%		60	12.7	0.38	3.0%	0.36	2.9%
	Serum 2	60	22.2	0.32	1.4%	0.36	1.6%		60	22.3	0.33	1.5%	0.37	1.7%
	Serum 3	60	30.9	0.53	1.7%	0.66	2.1%		60	31.1	0.36	1.2%	0.48	1.5%

Patient Comparison

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

Analyte	Specimen	Unit	n	a	b	r	range	mean X	mean Y
Calcium	Serum/Plasma	mg/dL	160	0.0	0.989	0.985	7.1 - 10.6	9.26	9.13
	Urine	mg/dL	74	-0.2	1.007	0.998	2.4 - 15.2	8.45	8.3
Chloride	Serum/Plasma	mmol/L	160	1.0	0.988	0.935	98.2 - 127.5	107.3	107.0
	Urine	mmol/L	78	-5.1	1.049	0.999	22.4 - 289	126.8	127.9
	CSF	mmol/L	44	-3.4	1.024	0.985	113.8 - 152.4	126.5	126.1
Potassium	Serum/Plasma	meq/L	160	0.13	0.969	1.000	3.20 - 10.82	5.02	5.00
	Urine	meq/L	80	0.01	0.993	1.000	3.48 - 136.0	50.5	50.2
Sodium	Serum/Plasma	meq/L	160	9.1	0.930	0.938	131.8 - 159.1	141.0	140.3
	Urine	meq/L	78	-0.3	1.000	1.000	16.9 - 288.1	118.2	117.8
Total CO2	Serum/Plasma	mmol/L	160	1.2	0.949	0.953	9.5 - 29.1	23.3	23.2

Wynn Stocking

Wynn Stocking Manager of Regulatory Affairs Elan Diagnostics

20 August, 1999

{2}------------------------------------------------

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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling a stylized caduceus or a series of flowing ribbons.

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: K992844

Trade Name: HiChem® ISE Electrolyte Buffer Regulatory Class: II Product Code: JGS, CEM, CGE, 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 Putman

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

{4}------------------------------------------------

510(k) Number (if known): K992844

Device Name:

HiChem® ISE Electrolyte Buffer

Indications For Use:

This reagent is intended for professional use only.

Respectfully.

Wynn Stocking Regulatory Affairs Manager Elan Diagnostics

10 November, 1999

Jean Coopr

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K992844

(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

§ 862.1665 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.