The product encompassed by this 510(k) submission is a Class II (81KRZ) In Vitro Diagnostic Solution manufactured by ALKO Diagnostic Corporation. The tHb Cal Standard is intended to serve as direct replacement to like named product manufactured by Instrumentation Laboratory Company. ALKO Product A331-50 (tHb Cal Standard) is equivalent to Instrumentation Laboratory product 33150-50 (Cal Dye and Reference Standard). ALKO uses a similar composition, description and packaging design as that used by Instrumentation Laboratory Company in its products.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study findings for the ALKO Diagnostics Corporation's tHb Cal Standard, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the ALKO tHb Cal Standard are implicitly defined by its equivalence to the predicate device, Instrumentation Laboratory's Cal Dye™ Reference Standard, and its ability to consistently calibrate CO-Oximeters and Oximeters within acceptable ranges. The performance metrics reported are precision (as Total and Run-to-Run CV%) and comparative agreement with assayed values and the predicate device.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance and Comparisons
Precision	The ALKO tHb Cal Standard should demonstrate precision comparable to or better than established industry standards for similar calibrators and allow the CO-Oximeter/Oximeter to maintain precision for control analyses. (Specific numerical criteria are not explicitly stated, but typical expectations for calibrators in high-precision medical devices are very low CV%).	Precision Data (IL 482 analyzer, calibrated with ALKO tHb Cal Standard, using IL CO-OX controls):- Level 1 (Mean 16.9): Total CV% 0.6993, Run to Run CV% 0.3826- Level 2 (Mean 13.8): Total CV% 0.8340, Run to Run CV% 0.5857- Level 3 (Mean 7.2): Total CV% 1.0758, Run to Run CV% 0.7435These CV% values are very low, indicating high precision.
Comparative Data (tHb Cal Standard vs. Predicate)	The ALKO tHb Cal Standard should yield total hemoglobin (tHb) values that are effectively equivalent to those obtained with the IL Cal Dye™ Reference Standard when measured on the same IL CO-Oximeters/Oximeters. The mean tHb values, standard deviations, and CV% should be very similar, and the measured range (min-max) should encompass or align closely with the assayed values and the predicate's performance. Consistency across different instrument models (IL 282, IL 482) is also a criterion.	On IL 282:- IL 33150 (Predicate): Mean 14.7, STD 0.0653, CV% 0.4450, tHb min.-max. 14.6-14.8, Assay Value 14.8- ALKO A331-50: Mean 15.0, STD 0.0499, CV% 0.3316, tHb min.-max. 15.0-15.1, Assay Value 15.0On IL 482:- IL 33150 (Predicate): Mean 14.9, STD 0.0730, CV% 0.4901, tHb min.-max. 14.8-15.0, Assay Value 14.9- ALKO A331-50: Mean 14.8, STD 0.0442, CV% 0.2993, tHb min.-max. 14.7-14.8, Assay Value 14.8The mean tHb values, SDs, and CV% are very close between the ALKO and IL products on both instruments, demonstrating strong agreement and comparability. The measured ranges are also consistent with the respective assayed values.
Functional Equivalence (with predicate)	When used to calibrate IL CO-Oximeters/Oximeters, the ALKO tHb Cal Standard should enable the instrument to produce mean values for various blood gas parameters (tHb, %O2Hb, %COHb, %MetHb, O2 Ct, %RHb) from control samples that fall within the assayed control ranges and are comparable to results obtained when the instrument is calibrated with the predicate IL Cal Dye™ Reference Standard.	On IL 282 & IL 482: For all three control levels and across all measured parameters (tHb, %O2Hb, %COHb, %MetHb, O2 Ct, %RHb), the mean values obtained when calibrating with ALKO tHb Cal Standard are very similar to those obtained with the IL Cal Dye™ Reference Standard. Critically, these mean values consistently fall within the specified "Assayed Control Values" ranges, which broadens the acceptance window. The results demonstrate that the ALKO calibrator allows the instruments to perform functionally equivalently to calibration with the predicate.

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

Precision Test Set: The precision study used three levels of IL CO-OX controls. Each level was analyzed 3 times per run, for 5 runs, after a separate calibration for each run. This totals 15 data points (N=15) for each level for "Total" precision, and 5 data points (N=5) for "Run to Run" precision (representing the 5 runs).
Comparative Data Test Set: For both the IL 282 and IL 482 analyzers, 15 measurements (N=15) were taken for both the IL predicate product and the ALKO product.
Functional Tests Test Set: Three levels of IL CO-OX controls were measured in triplicate (meaning 3 measurements per level). This was done after calibrating separately with the ALKO standard and the IL predicate standard. (The exact total number of individual measurements for functional tests across all parameters is not explicitly stated as 'N' in a table, but it implies 3 measurements * 3 levels * 2 calibration methods * number of parameters).
Data Provenance: The data was generated by ALKO Diagnostic Corporation, 333 Fiske Street, Holliston, MA 01746, USA. This indicates the testing was done in the USA. The study appears to be prospective as it involves direct testing and comparison of the ALKO product against the predicate and control materials with specific measurement protocols.

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

The document does not mention the use of experts to establish ground truth for the test set. Instead, the ground truth is established through:

Assayed values: For the comparative data and functional tests, "Assay Value" or "Assayed Control Values" are provided, which represent the target or expected values for the control materials. These values are typically established by the control manufacturer using reference methods or multiple laboratory testing, not by ad-hoc experts for this specific study.

4. Adjudication Method for the Test Set

There is no mention of an adjudication method in the context of expert review. The study relies on direct quantitative comparison of instrument readings against established assay values or predicate device performance.

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

This is not applicable as the device is an in-vitro diagnostic solution (calibrator) for an instrument, not an AI-powered diagnostic imaging or decision support tool that is interpreted by human readers.

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

This is standalone performance in the context of an IVD calibrator. The performance of the ALKO tHb Cal Standard is assessed by its direct functional impact on the IL CO-Oximeters/Oximeters, allowing them to accurately measure control samples. There is no "human-in-the-loop" interpretation beyond the operation of the instrument itself. The study objective is to show the calibrator functions on its own to enable accurate instrument readings.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth used consists of:

Assayed Values: These are reference values provided by the manufacturer of the IL CO-OX controls for specific parameters (tHb, %O2Hb, etc.). These are typically established through rigorous analytical testing using reference methods.
Predicate Device Performance: The performance of the Instrumentation Laboratory Cal Dye™ Reference Standard is used as a direct benchmark, as the ALKO product is intended to be a direct replacement and functionally equivalent. The equivalence to an already marketed and presumably validated product serves as a form of "ground truth" for comparative studies.

8. The Sample Size for the Training Set

This is not applicable. The ALKO tHb Cal Standard is an in-vitro diagnostic reagent (calibrator), not an algorithm or AI model that requires a training set. The "composition, description and packaging design" mention indicates a manufacturing process, not a machine learning process.

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

This is not applicable as there is no training set mentioned for this product.

Summary

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DEC 1 8 1996

Image /page/0/Picture/1 description: The image shows the logo for ALKO Diagnostic Corporation. The logo consists of a black triangle with the word "ALKO" underneath it. Below the company name is the text "A Life Sciences International Company".

A Life Sciences International Company

K962864

510(k) Summary

tHb Cal Standard

for Instrumentation Laboratory CO-Oximeters and Oximeters.

The product encompassed by this 510(k) submission is a Class II (81KRZ) In Vitro Diagnostic Solution manufactured by ALKO Diagnostic Corporation, 333 Fiske Street, Holliston, MA 01746. The tHb Cal Standard is intended for use in calibrating the total hemoglobin channel of the IL CO-Oximeters and Oximeters. Instrumentation Laboratory Company is the original equipment manufacturer (OEM) of the analyzer and of predicate Cal Dye™ Reference Standard which is necessary for calibrating the total hemoglobin channel on the IL CO-Oximeters and/Oximeters.

The tHb Cal Standard is intended to serve as direct replacement to like named product manufactured by Instrumentation Laboratory Company. ALKO Product A331-50 (tHb Cal Standard) is equivalent to Instrumentation Laboratory product 33150-50 (Cal Dyeand Reference Standard).

ALKO uses a similar composition, description and packaging design as that used by Instrumentation Laboratory Company in its products. ALKO has shown performance equivalence of its product to Instrumentation Laboratory Company's product in the following manner:

O Through functional tests where results were obtained on Instrumetation Laboratory CO-Oximeters/Oximeters with ALKO product and were compared with results obtained on the same analyzer calibrated with Instrumentation Labratory product.
Through a precision study where ALKO product was used on an Instrumetation Laboratory O Analyzer and samples were measured over _ 5 _ runs.
O Through a comparative analysis where tHb Cal Standard and IL Cal Dye™ Reference Standard were measured and compared with the assayed tHb values.

A summary of the results of these studies follows:

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Page 2/ ALKO 510 (k) Summary for IL Cal Dye™ Reference Standard

PERFORMANCE CHARACTERISTICS

1. Precision Data

Precision data were collected from the analysis of three levels of IL CO-OX controls (Human Hemoglobin based), 3 times per run, one run per day for 5 days, on a 482 analyzer calibrated with ALKO tHb Cal Standard. A separate calibration was performed prior to each run.

tHb
Level		N	Mean	STD	CV%	Min	Max
1	Total	15	16.9	0.1181	0.6993	16.8	17.2
	Run to Run	5	16.9	0.0646	0.3826	16.8	17.0
2	Total	15	13.8	0.1147	0.8340	13.6	13.9
	Run to Run	5	13.8	0.0806	0.5857	13.6	13.9
3	Total	15	7.2	0.0772	1.0758	7.1	7.4
	Run to Run	5	7.2	0.0533	0.7435	7.1	7.3

2. Comparative Data

Comparative data were collected from the analysis of ALKO and IL tHb Cal Standards measured on IL 282 and 482 Analyzers.

Instrument	Product P/N, Lot No	N	Mean	STD	CV%	tHb min.- max.	Assay Value
on IL 282	IL 33150, lot N0931981	15	14.7	0.0653	0.4450	14.6 - 14.8	14.8
	ALKO A331-50, lot 10624	15	15.0	0.0499	0.3316	15.0 - 15.1	15.0
on IL 482	IL 33150, lot N1257163	15	14.9	0.0730	0.4901	14.8 - 15.0	14.9
	ALKO A331-50, lot 50128	15	14.8	0.0442	0.2993	14.7 - 14.8	14.8

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3. Functional Tests

Functional tests of ALKO tHb Cal Standard were performed on IL 282 and 482 Analyzers and compared to IL Cal Dye™ Reference Standard. Both analyzers were calibrated with ALKO and IL tHb Standards separately. Three levels of IL CO-OX controls (Human Hemoglobin based) were measured in triplicate. The mean values are shown below.

		tHb(g/dL)	%O2Hb	%COHb	%MetHb	O2 Ct(Vol%)
Calibratedwith IL CalDye™ReferenceStandard	Level 1	17.2	39.3	60.4	0.2	9.4
	Level 2	12.8	96.3	3.7	0.5	17.2
	Level 3	6.4	76.0	24.1	0.2	6.7
Calibratedwith ALKOtHb CalStandard	Level 1	17.4	39.4	60.4	0.3	9.5
	Level 2	13.0	96.1	4.0	0.5	17.4
	Level 3	6.5	75.8	24.3	0.4	6.8
AssayedControlValues	Level 1	16.6-17.6	37.1-41.1	58.6-62.0	-0.9-3.1	8.5-10.5
	Level 2	12.3-13.3	93.5-98.5	1.9-5.3	-1.1-2.9	16.3-18.7
	Level 3	6.0-7.0	73.7-77.7	22.1-25.5	-1.0-3.0	6.2-7.4

a) IL 282 Analyzer

b) IL 482 analyzer

		tHb(g/dL)	%O2Hb	%COHb	%MetHb	O2 Ct (Vol%)	% RHb
Calibratedwith IL CalDye™ReferenceStandard	Level 1	16.8	39.0	60.5	0.1	9.1	0.4
	Level 2	13.7	97.3	2.2	0.2	18.5	0.3
	Level 3	7.1	77.3	22.4	0.2	7.6	0.1
Calibratedwith ALKOtHb CalStandard	Level 1	16.9	39.1	60.1	0.4	9.2	0.4
	Level 2	13.8	97.1	2.1	0.3	18.6	0.4
	Level 3	7.1	77.2	22.4	0.2	7.6	0.3
AssayedontrolValues	Level 1	16.6 to17.6	35.6 to39.6	59.6 to63.0	-0.8 to3.2	8.1 to10.1	-1.3 to1.1
	Level 2	13.3 to14.3	93.4 to98.4	1.5 to4.9	-0.9 to3.1	17.4 to19.8	-1.5 to0.9
	Level 3	6.7 to 7.7	74.1 to78.1	21.0 to24.4	-0.6 to3.4	7.1 to8.3	-1.5 to0.9

A Worldwide Supplier of Blood Gas and ISE

ALKO Diagnostic Corporation . 333 Fiske Street . Holliston, MA . 01746-2048 . USA . Phone: (508) 429-4600 . Fax: (508) 429-4900

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Conclusion

ALKO manufactures products that serve as functional equivalents to consumable distributed by Original Equipment Manufacturer. All such products are manufactured with the intent of complying with the Good Manufacturing Practice Regulations.

As previously stated the product encompassed by this request serves as a functional equivalent to the product currently manufactured and marketed by Instrumentation Laboratory of Lexington, MA USA. We believe that Instrumentation Laboratory has received 510 (k) market approval given that they are currently distributing the IL CO-Oximeter instruments and related consumable domestically. The previously described labeling and performance verification should provide adequate documentation as to the equivalence of the ALKO Product.

I hope you find the documentation provided informative and helpful.

Janet A. McGrath

Regulatory Affairs

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Regulation Number and Section

§ 864.8165 Calibrator for hemoglobin or hematocrit measurement.

(a)
Identification. A calibrator for hemoglobin or hematocrit measurement is a device that approximates whole blood, red blood cells, or a hemoglobin derivative and that is used to set instruments intended to measure hemoglobin, the hematocrit, or both. It is a material whose characteristics have been precisely and accurately determined.(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 § 864.9.