The products encompassed by this request are intended for in vitro diagnostic use and are intended for use in the quantitative determinations of Nat K . Cl . and CO., Beckman Instrument is the Original Equipment Manufacturer of the Chemistry Analyzers and of the predicate Reagents. The Beckman Chemistry Analyzers perform a broad array of tests. ALKO manufactures the ISE Reagents, wherein samples are analyzed for quantitative determinations of Nat, K, Cl and CO2 by ISE method. These Reagents are intended to be used with equivalent Beckman Chemistry Analyzers. As such, ALKO products are intended to serve as direct replacements to like named products manufactured by Beckman Instrument Inc.

The Electrolyte Buffer is intended to provide constant ionic strength for measuring electrolytes in the samples. As such, it is diluted with Wash Solution and introduced into the sample and/or calibrator, for quantitative determination of Nat, K*, Cl and CO., The Electrolyte Reference Reagent is intended to provide reference points for Na , K , Cl and CO2. The CO2 Acid Reagent is intended to release CO2 from serum and plasma samples and/or calibrators. The CO, Alkaline Buffer is to provide a constant CO, concentration as reference for the CO, Electrode. The Wash Concentrate is intended to be diluted with deionized water. The prepared Wash Solution is used to wash the systems sample flow path and to dilute reagents on equivalent Beckman CX® Systems.

Device Description

The products encompassed by this 510(k) submission are Class II (75JIX) In Vitro Diagnostic Solutions manufactured by ALKO Diagnostic Corporation, 333 Fiske Street, Holliston, MA 01746. The Reagents are intended for use on equivalent Beckman Analyzers. Beckman Instrument is the original equipment manufacturer (OEM) of the analyzers and of predicate reagents which are necessary for the continued operation and use of the analyzers.

Information herein will support ALKO's position for the intended use of these products to the equivalent Beckman Chemistry Analyzers. The Beckman Chemistry Añalyzers perform a broad array of tests. ALKO manufactures the ISE Reagents, wherein samples are analyzed for quantitative determinations of Nat, K', Cl ' and CO, by ISE method. These Reagents are intended to be used with equivalent Beckman Chemistry Analyzers. As such, ALK O products are intended to serve as direct replacements to like named products manufactured by Beckman Instrument Inc.

The Electrolyte Buffer is intended to provide constant ionic strength for measuring electrolytes in the samples. As such, it is diluted with Wash Solution and introduced into the sample and/or calibrator, for quantitative determination of Nat, K., Cl - and CO2. The Electrolyte Reference Reagent is to provide reference points for Nat, K*, Cl and CO, The CO, Acid Reagent is to release CO, from serum and plasma samples and/or librators. The CO, Alkaline Buffer is to provide a constant CO2 concentration as reference for the CO2 * Electrode. The Wash Concentrate is intended to be diluted with de-ionized water. The prepared Wash Solution is used to wash the systems sample probe and to dilute reagents on equivalent Beckman CX® Systems.

ALKO product A443-325 (Electrolyte Buffer) is equivalent to Beckman Instrument product 443325 . (Electrolyte Buffer).
ALKO product A443-315 (Electrolyte Reference Reagent), is equivalent to Beckman Instrument product . 443315 (Electrolyte Reference Reagent).
ALKO product A443-330 (CO2 Acid Reagent), is equivalent to Beckman Instrument product 443330 . (CO2 Acid Reagent).
ALKO product A443-320 (CO2 Alkaline Buffer), is equivalent to Beckman Instrument product 443320 . (CO2 Alkaline Buffer).
ALKO product A443-335 (Wash Concentrate), is equivalent to Beckman Instrument product 443335 . (Wash Concentrate).

ALKO uses a similar composition, description and packaging design as that used by Beckman Instrument Inc. in its products.

AI/ML Overview

Acceptance Criteria and Study for ALKO Reagents on Beckman CX® Series Analyzers

This document describes the acceptance criteria and study proving equivalence for ALKO Reagents when used on Beckman CX® Series and equivalent analyzers. The goal is to demonstrate that ALKO products can serve as direct replacements for Beckman Instrument Inc. reagents for quantitative determination of Na+, K+, Cl-, and CO2 by ISE method.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the performance characteristics demonstrated to be equivalent to the predicate Beckman reagents. For the purposes of this summary, the key performance characteristics are precision and correlation with Beckman reagents.

Acceptance Criteria for Precision (implicitly defined by demonstrated performance)

The acceptance criteria for precision are implicitly based on the observed Coefficient of Variation (CV%) values, which are considered acceptable for quantitative electrolyte measurement in clinical diagnostics.

Analyte	Sample Type/Level	Metric	Acceptance Criteria (Implied)	Reported Performance (Total CV%)
Na+	Serum (Normal)	CV%	Clinically acceptable range	0.9596%
Na+	Serum (Abnormal)	CV%	Clinically acceptable range	0.7698%
Na+	Urine (Level 1)	CV%	Clinically acceptable range	1.2544%
Na+	Urine (Level 2)	CV%	Clinically acceptable range	1.0267%
K+	Serum (Normal)	CV%	Clinically acceptable range	1.1071%
K+	Serum (Abnormal)	CV%	Clinically acceptable range	0.8462%
K+	Urine (Level 1)	CV%	Clinically acceptable range	1.2944%
K+	Urine (Level 2)	CV%	Clinically acceptable range	1.2567%
Cl-	Serum (Normal)	CV%	Clinically acceptable range	1.2643%
Cl-	Serum (Abnormal)	CV%	Clinically acceptable range	0.8451%
Cl-	Urine (Level 1)	CV%	Clinically acceptable range	1.3918%
Cl-	Urine (Level 2)	CV%	Clinically acceptable range	1.0690%
CO2	Serum (Normal)	CV%	Clinically acceptable range	4.0549%
CO2	Serum (Abnormal)	CV%	Clinically acceptable range	1.9268%

Acceptance Criteria for Correlation with Beckman Reagents (implicitly defined by demonstrated performance)

The acceptance criteria for correlation are implicitly based on high R-squared values (close to 1), slopes close to 1, and intercepts close to 0, indicating strong agreement and similar performance to the Beckman reagents.

Analyte	Analyzer (CX®3)	Acceptance Criteria (Implied)	Reported Performance (R-Squared)	Reported Performance (Slope)	Reported Performance (Intercept)
Na+	CX®3	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9992	1.0048	-0.6344
K+	CX®3	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9995	0.9840	0.0846
Cl-	CX®3	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9991	0.9801	1.5534
CO2	CX®3	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9956	0.9738	0.6117
Na+	CX®5	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9961	0.9727	3.7055
K+	CX®5	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9993	0.9807	0.0447
Cl-	CX®5	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9991	0.9369	5.0960
CO2	CX®5	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9988	0.9885	0.2429
Na+	Urine (CX®3)	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9997	0.9984	0.0968
K+	Urine (CX®3)	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9991	0.9602	1.0587
Cl-	Urine (CX®3)	R² > 0.99, Slope ≈ 1, Intercept ≈ 0	0.9978	0.9764	1.7695

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

Precision Study:

Sample Size (Test Set): For each analyte (Na+, K+, Cl-, CO2), there were 60 measurements for each control level (serum normal, serum abnormal, urine level 1, urine level 2) for "Total" precision, derived from 20 runs performed in triplicate per run. For "Run to Run" precision, N=20 (representing 20 individual runs).
Data Provenance: The document does not explicitly state the country of origin. Given the FDA 510(k) submission, it is likely that the study was conducted in the US or under US regulatory standards. The study appears to be prospective as it involved measurements over a defined period (20 runs over 30 days).

Correlation Study:

Serum/Plasma Samples (Beckman CX®3): 68+ serum and plasma samples were used across the analytes, with specific N values: Na+ (72), K+ (74), Cl- (77), CO2 (68).
Serum Samples (Beckman CX®5): 34+ serum samples were used across the analytes, with specific N values: Na+ (38), K+ (40), Cl- (34), CO2 (38).
Urine Samples (Beckman CX®3): 54+ urine samples were used across the analytes, with specific N values: Na+ (54), K+ (54), Cl- (55).
Data Provenance: The document does not explicitly state the country of origin. This study appears to be prospective as it involved measuring samples with ALKO reagents and comparing them to measurements with Beckman reagents on the same analyzers.

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

This type of study (comparative performance of IVD reagents) does not typically involve human experts establishing "ground truth" in the same way imaging or clinical decision support AI devices do. The "ground truth" or reference standard for this study is the performance of the predicate Beckman reagents on the same analyzer. There are no human experts involved in determining the analytical accuracy or precision of the measurements.

4. Adjudication Method for the Test Set

Not applicable. As described above, this study focuses on analytical performance characteristics (precision, correlation) of diagnostic reagents, not clinical interpretation that would require expert adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This study pertains to in vitro diagnostic reagents, which measure analytes (Na+, K+, Cl-, CO2) directly. MRMC studies are typically performed for clinical decision support or imaging interpretation devices where human interpretation is a critical component influencing diagnostic accuracy.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, this study presents standalone performance of the ALKO reagents in conjunction with the Beckman analyzers. The measurements are performed by the automated ISE module of the analyzers, calibrated with either ALKO or Beckman reagents, without human interpretation of the raw analytical results being the primary endpoint of the study. The performance characteristics (precision, correlation) are inherent to the reagent-analyzer system.

7. The Type of Ground Truth Used

The "ground truth" for the correlation study is established by the measurements obtained using the predicate Beckman reagents on the same Beckman CX® Series analyzers. The study aims to show that the ALKO reagents produce results that are statistically equivalent and highly correlated with those from the established and legally marketed Beckman reagents. For the precision study, there is no external "ground truth"; rather, the assay's own reproducibility is assessed.

8. The Sample Size for the Training Set

This document describes a performance validation study for in vitro diagnostic reagents. In this context, there isn't a "training set" in the sense of machine learning algorithms. The reagents themselves are "trained" or optimized during their development and manufacturing process to meet certain specifications. The data presented here are validation data used to demonstrate that the final manufactured product performs as intended and equivalently to the predicate.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" in the context of a machine learning algorithm. The "ground truth" for the development of ALKO reagents would involve internal R&D and quality control processes to ensure the chemical properties and performance characteristics meet design specifications and are comparable to market leaders like Beckman.

Summary

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SEP 1998

K982501

510(k) Summary for ALKO Reagents on Beckman CX® Series and Equivalent Analyzers

The Electrolyte Buffer is intended to provide constant ionic strength for measuring electrolytes in the samples. As such, it is diluted with Wash Solution and introduced into the sample and/or calibrator, for quantitative determination of Nat, K., Cl - and CO2. The Electrolyte Reference Reagent is to provide reference points for Nat, K*, Cl and CO, The CO, Acid Reagent is to release CO, from serum and plasma samples and/or librators. The CO, Alkaline Buffer is to provide a constant CO2 concentration as reference for the CO2 * Electrode. The Wash Concentrate is intended to be diluted with de-ionized water. The prepared Wash Solution is used to wash the systems sample probe and to dilute reagents on equivalent Beckman CX® Systems.

ALKO product A443-325 (Electrolyte Buffer) is equivalent to Beckman Instrument product 443325 . (Electrolyte Buffer).
ALKO product A443-315 (Electrolyte Reference Reagent), is equivalent to Beckman Instrument product . 443315 (Electrolyte Reference Reagent).
ALKO product A443-330 (CO2 Acid Reagent), is equivalent to Beckman Instrument product 443330 . (CO2 Acid Reagent).
ALKO product A443-320 (CO2 Alkaline Buffer), is equivalent to Beckman Instrument product 443320 . (CO2 Alkaline Buffer).
ALKO product A443-335 (Wash Concentrate), is equivalent to Beckman Instrument product 443335 . (Wash Concentrate).

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ALKO uses a similar composition, description and packaging design as that used by Beckman Instrument Inc. in its products. ALKO has shown performance equivalence of its products to Beckman Instrument products in the following manner:

Through a method comparison where results obtained on an equivalent Beckman Chemistry O Analyzer, calibrated with ALKO products and compared with results obtained on the same Analyzer calibrated with Beckman Instrument products; and
Through a precision study where ALKO products were installed on an equivalent Beckman o Chemistry Analyzer and samples were measured one run per day for a defined period as stated below. A summary of the results of these studies follows:

PERFORMANCE CHARACTERISTICS

Precision Data

Precision data were collected from the analysis of two levels of serum and urine controls, measured in triplicate per run, one run per day for a total of 20 runs over 30 days on the ISE Module of Beckman CX®3, calibrated with all ALKO reagents.

		N	Mean	STD	CV%	Min	Max
Na+	Total	60	137.4	1.3186	0.9596	135.1	140.0
	Run to Run	20	137.4	1.2477	0.9080	135.5	139.7
K+	Total	60	4.17	0.0461	1.1071	4.08	4.28
	Run to Run	20	4.17	0.0430	1.0323	4.11	4.24
Cl-	Total	60	100.5	1.2705	1.2643	97.0	103.1
	Run to Run	20	100.5	1.0149	1.0099	98.5	102.3
CO2	Total	60	15.1	0.6136	4.0549	14.1	16.6
	Run to Run	20	15.1	0.5805	3.8425	14.3	16.4

Serum Level : Normal

Serum Level : Abnormal

		N	Mean	STD	CV%	Min	Max
Na+	Total	60	151.2	1.1638	0.7698	147.5	153.1
	Run to Run	20	151.2	1.0763	0.7119	148.7	152.7
K+	Total	60	7.32	0.0620	0.8462	7.12	7.42
	Run to Run	20	7.32	0.0594	0.8120	7.14	7.40
Cl-	Total	60	112.1	0.9476	0.8451	109.6	113.9
	Run to Run	20	112.1	0.8375	0.7468	110.4	113.4
CO2	Total	60	25.5	0.4917	1.9268	24.5	26.8
	Run to Run	20	25.5	0.4393	1.7214	24.9	26.4

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		N	Mean	STD	CV%	Min	Max
Na+	Total	60	81.0	1.0163	1.2544	79.4	83.6
	Run to Run	20	81.0	0.9591	1.1838	79.7	82.9
K+	Total	60	30.2	0.3910	1.2944	29.3	30.9
	Run to Run	20	30.2	0.3799	1.2576	29.5	30.9
Cl-	Total	60	81.3	1.1310	1.3918	78.5	83.4
	Run to Run	20	81.3	0.9046	1.1133	79.6	82.7

Urine Level 2

		N	Mean	STD	CV%	Min	Max
Na+	Total	60	175.5	1.8021	1.0267	171.8	179.6
	Run to Run	20	175.5	1.7356	0.9888	172.3	179.1
K+	Total	60	100.4	1.2619	1.2567	97.0	103.2
	Run to Run	20	100.4	1.2280	1.2229	97.1	102.9
Cl-	Total	60	203.4	2.1740	1.0690	199.5	209.0
	Run to Run	20	203.4	2.0802	1.0228	200.5	208.7

Correlation with Beckman Reagents

Linear Regression Analyses were performed using the Beckman data as the Independent X Variable and ALKO Data as the Dependent Y Variable in the equation Y = a + bX.

Serum(Plasma) Samples (Beckman CX®3):

Correlation data were collected from 68+ serum and plasma samples for Nat/K+/C1/CO2, measured on the ISE Module of the Beckman CX®3 System, calibrated with ALKO as compared with Beckman reagents separately.

	Na	K	Cl	CO2
N	72	74	77	68
Slope	1.0048	0.9840	0.9801	0.9738
Intercept	-0.6344	0.0846	1.5534	0.6117
R Squared	0.9992	0.9995	0.9991	0.9956
Range	100 - 200	1 - 15	50 - 200	5 - 40

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Serum (Plasma) Samples (Beckman CX®5):

Correlation data were collected from 34+ serum samples for Na+/K+/Cl-/CO2, measured on the ISE Module of the leckman CX®5 System, calibrated with ALKO as compared with Beckman reagents separately.

	Na	K	Cl	CO2
N	38	40	34	38
Slope	0.9727	0.9807	0.9369	0.9885
Intercept	3.7055	0.0447	5.0960	0.2429
R Squared	0.9961	0.9993	0.9991	0.9988
Range	100 - 200	1 - 15	50 - 200	5 - 40

Urine Samples (Beckman CX®3):

Correlation data were collected from 54+ urine samples for Na+/K+/ C1', measured on the ISE Module of the Beckman CX®3 System, calibrated with ALKO as compared with Beckman reagents separately.

	Na	K	Cl
N	54	54	55
Slope	0.9984	0.9602	0.9764
Intercept	0.0968	1.0587	1.7695
R Squared	0.9997	0.9991	0.9978
Range	10 - 200	2 - 200	15 - 300

I hope you find this information useful and informative.

Janet C. Metcalf

7/6/92
(date prepared)

Yanet A, McGrath Regulatory Affairs

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Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with three lines forming the snake and staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the emblem.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 1998 SEP

Janet A. McGrath . Regulatory Affairs Specialist Alko Diagnostic Corporation 333 Fiske Street 01746 Holliston, Massachusetts

K982501 Re : Electrolyte Buffer A443-325, and Reference Reagent Requlatory Class: II Product Code: JIX Dated: July 16, 1998 Received: July 20, 1998

Dear Ms. McGrath:

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 requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. पै 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 requlation (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 requlations.

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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 onthe 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 Litman

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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510(k) Number (if known):

Device Name: Reagents on Equivalent Beckman Chemistry Analyzers

Indication For Use:

Concurrence of CDRH, Office of Device Evaluation (ODE (Division Sign-Off Division of Clinical Laboratory بارا vice 510(k) Number Prescription Use OR Over-The-Counter Use (Per 21 CFR 801.109) (Optional Format 1-2-96)

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

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Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special 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.