The products encompassed by this request are intended for in-vitro diagnostics use and for use in calibrating the electrodes and flushing the sample flow path of the equivalent Corning 6X4 Series Electrolyte Analyzers. Corning (undergone several owner and name changes incl.: Corning Glass, Ciba-Corning, Chiron, and currently Bayer) is the Original Equipment Manufacturer (OEM) of the analyzers and the predicate reagents. Mission reagents are intended to serve as direct replacements to like named products manufactured by Corning (under the label of current owner, Bayer). The products encompassed are to be handled using normal laboratory precautions.

Device Description

The Calibrators for the Corning Electrolyte Instruments are aqueous reagents with salts added to obtain desired analyte levels to provide calibration of the electrodes and rinse the sample path. Mission uses a similar composition, description and packaging as that used by Corning in its products.

AI/ML Overview

This medical device submission (K020596) describes the performance of Mission Diagnostic Reagents for Corning 6X4 Electrolyte Analyzers. The submission establishes substantial equivalence to existing Corning calibrators.

Here's an analysis of the provided text to answer your questions:

Acceptance Criteria and Device Performance Study

The study evaluates the performance of Mission Diagnostic reagents (calibrators) as direct replacements for Corning's original calibrators on Corning 6X4 Electrolyte Analyzers. The acceptance criteria are implicitly defined by demonstrating "performance equivalence" through precision data and correlation with Corning reagents. The study aims to show that the Mission reagents produce results comparable to the predicate Corning reagents.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Analyte	Device	Acceptance Criteria (Implicit)	Reported Performance (Mission Reagents)
Precision	Na	614	CV% within acceptable range for clinical use (not explicitly stated, but inferred from predicate device performance)	QC1: 0.79%, QC2: 0.50%, QC3: 0.50%
	K	614	CV% within acceptable range for clinical use	QC1: 1.67%, QC2: 0.46%, QC3: 0.92%
	Na	644	CV% within acceptable range for clinical use	QC1: 0.56%, QC2: 0.85%, QC3: 0.72%
	K	644	CV% within acceptable range for clinical use	QC1: 1.13%, QC2: 0.40%, QC3: 0.68%
	Cl	644	CV% within acceptable range for clinical use	QC1: 1.40%, QC2: 1.99%, QC3: 1.85%
	Na	654	CV% within acceptable range for clinical use	QC1: 1.75%, QC2: 1.06%, QC3: 1.32%
	K	654	CV% within acceptable range for clinical use	QC1: 1.49%, QC2: 0.65%, QC3: 1.14%
	Li	654	CV% within acceptable range for clinical use	QC1: 8.89%, QC2: 3.27%, QC3: 3.75%
Correlation	Na	All	Slopes of ~1.0 and R² ≥ 0.99	614: Slope 1.00, R² 1.00; 644: Slope 1.03, R² 1.00; 654: Slope 0.97, R² 1.00
	K	All	Slopes of ~1.0 and R² ≥ 0.99	614: Slope 1.01, R² 1.00; 644: Slope 1.04, R² 1.00; 654: Slope 1.07, R² 1.00
	Cl	644	Slopes of ~1.0 and R² ≥ 0.99	Slope 0.97, R² 1.00
	Li	654	Slopes of ~1.0 and R² ≥ 0.99	Slope 0.96, R² 0.99

Note: The acceptance criteria for precision are not explicitly stated as numerical cut-offs but are implied by demonstrating performance equivalence with the predicate device, which would typically involve showing CV% values are within clinically acceptable limits for the analytes and the instrument type.

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

Precision Data (Test Set):
- Sample Size: For each analyte and QC level across the different Corning instruments (614, 644, 654), N typically ranged from 21 to 24 measurements. For example, for Na on Corning 614, N=24 for each of the three QC levels.
- Data Provenance: The data was collected from "QC samples (or control material)" measured over a minimum of 7 days on equivalent Corning analyzers where Mission products were installed. The control materials are standardized solutions, not patient data from a specific country. This is prospective data collection focused on the device's performance.
Correlation Data (Test Set):
- Sample Size:
  - Na: 50 human serum samples per instrument type (614, 644, 654).
  - K: 60 human serum samples per instrument type (614, 644, 654).
  - Cl: 50 human serum samples on Corning 644.
  - Li: 30 human serum samples on Corning 654.
- Data Provenance: The data used "human serum samples." These samples were "spiked with LiCl to obtain a base Li concentration" and then further "spiked to yield varying concentrations of each of the measuring analytes." This setup indicates a controlled laboratory study using prepared samples, not necessarily from a specific country of origin in a retrospective manner. It appears to be prospective data collection for this comparison.

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

This type of submission for in-vitro diagnostic reagents does not typically involve human experts establishing "ground truth" in the way a diagnostic imaging study (e.g., radiologists interpreting images) would. The "ground truth" for the correlation study is implicitly established by the predicate Corning reagents run on the same analyzer. The study design involves comparing the results from the new Mission reagents against the results from the established Corning reagents, with the latter serving as the reference for equivalence. No information on experts is provided for this type of test.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

Not applicable to this type of in-vitro diagnostic reagent study. The "adjudication" is a direct numerical comparison of results between the test (Mission) and predicate (Corning) reagents on the same samples and instruments.

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 an in-vitro diagnostic device (reagent) and does not involve human readers interpreting cases or AI.

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

This is a standalone performance demonstration of the reagents themselves in an automated system, without human intervention needed for interpretation. The instrument (Corning 6X4 Electrolyte Analyzer) operates automatically once calibrated, and the reagents are a component of that automatic system. The study evaluates the performance of the reagents as an algorithm-only component of the analyzer.

7. The Type of Ground Truth Used

For Precision Data: The ground truth is the expected target concentration of the analyte in the control materials (QC1, QC2, QC3). The "Mean" values in the precision tables likely reflect the observed values relative to these expected targets.
For Correlation Data: The "ground truth" for comparison is the measurement obtained when the Corning reagents are used to calibrate the analyzer and measure the same human serum samples. This is a comparative ground truth established by the predicate device performance.

8. The Sample Size for the Training Set

There is no explicit mention of a "training set" in the context of machine learning. This submission is for reagents, not an AI/ML algorithm that requires training. The "performance characteristics" and "correlation" data described here are for the validation of the reagents. For the development of the reagents themselves, Mission Diagnostics would have conducted internal R&D, but that is not detailed as a "training set" in this regulatory submission.

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

Not applicable, as there is no "training set" in the context of an AI/ML algorithm being developed or assessed here. The submission is for chemical reagents.

Summary

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Page 27 of 45

510(k) Summary for Mission Diagnostic Reagents on Corning 6X4 Electrolyte Analyzers

K020596

1. Submitter's Name & Address Mission Diagnostics 331 Fiske St Holliston MA 01746 FAX: 508-429-0452
  MAR 2 6 2002

508-429-0450

In Process Establishment Registration Number:

Date of Preparation:

February, 19, 2002

Contact Person:

Linda Stundtner

QA/RA Manager

2. Identification of the Device:

Proprietary/Trade name:	Calibrating Material, Cal-Pak, Cal & Slope Standards
Common or usual name	Calibrators for ISE and/or pH/Blood Gas automated systems
Classification name:	Calibrator, secondary
Device Classification	II
Regulation Number:	21 CFR § 862.1150
Panel:	Chemistry (75)
Product Code:	JIT

1.

Predicate Device: 2.

Mission claims substantial equivalence to the Corning Calibrators listed below:

Mission Product	Corning Equivalent
CD-478541AD Cal-Pak for Corning 614	478541 614 Cal-Pak Na+/K+
CD-478548AD Cal Pak for Corning 634	478548 634 Cal-Pak Ca++/pH
CD-473510AD Cal-Pak for Corning 644	473510 644 Cal-Pak Na+/K+/Cl-
CD-473605AD Cal-Pak for Corning 654	473605 654 Cal-Pak Na+/K+/Li+

Device Description: 3.

The Calibrators for the Corning Electrolyte Instruments are aqueous reagents with salts added to obtain desired analyte levels to provide calibration of the electrodes and rinse the sample path.

4. Intended Use:

The reagents are intended for use on equivalent Corning Electrolyte Instruments to calibrate the . electrodes and flush the sample flow path.
Corning is the original equipment manufacturer (OEM) of the instruments and the predicate . reagents which are necessary for the continued operation and use of the instruments.
The Mission reagents are intended to serve as direct replacements to like named products . manufactured by Corning.
- The OEM products were originally released under the Corning name. .

510(k) Submission for Mission Diagnostics Reagents on Corning 6X4 Electrolyte Analyzers

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Corning has under gone several owner and name changes: . Corning Glass, Ciba-Corning, Chiron, and currently Bayer.
For the purposes of this 510(k) the OEM will be referred to as Corning. .
Mission uses a similar composition, description and packaging as that used by Corning in its . products, as shown in the packaging section of this submission.
Performance equivalence was shown in the following manner: .
- Precision data was collected from QC samples (or control material) measured over a o minimum of 7 days on an equivalent Corning analyzer where Mission products were installed.
- Correlation of serum sample results obtained on an equivalent Corning analyzer, o calibrated with Mission reagents and on the same analyzer calibrated with Corning reagents

A summary of the results of these studies follows:

Performance Characteristics:

Precision Data

Precision data were collected from the analysis of three levels of control materials, measured three r roolsion actu word over a minimum of 7 days on each Corning analyzer calibrated with all Mission reagents.

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Corning 614 Electrolyte Instrument Precison Data Table 1

Three levels of QC Material, Na, K precision values with Mission reagents.

Corning	614	Na
	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	24	112	0.9	110	113	0.79%
QC2	24	136	0.7	134	137	0.50%
QC3	24	159	0.8	158	161	0.50%

614 Corning

	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	24	1.93	0.032	1.85	1.99	1.67%
QC2	24	4.17	0.019	4.13	4.20	0.46%
QC3	24	6.58	0.060	6.49	6.72	0.92%

Corning 644 Electrolyte Instrument Precison Data Table 2

Three levels of QC Material, Na, K, CI precision values with Mission reagents.

Corning 644 Na

Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	24	108	0.6	107	109	0.56%
QC2	24	133	1.1	132	138	0.85%
QC3	23	157	1.1	155	159	0.72%

644 Corning

	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	24	1.93	0.022	1.89	1.98	1.13%
QC2	24	4.10	0.016	4.08	4.14	0.40%
QC3	23	6.51	0.044	6.45	6.60	0.68%

Corning 644 Cl

	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	24	81	1.1	79	84	1.40%
QC2	24	97	1.9	95	103	1.99%
QC3	23	128	2.4	125	135	1.85%

510(k) Submission for Mission Diagnostics Reagents on Corning 6X4 Electrolyte Analyzers

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Corning 654 Electrolyte Instrument Precison Data Table 3

Three levels of QC Material, Na, K, Li precision values with Mission reagents.

Corning	654

	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	21	109	1.9	104	113	1.75%
QC2	24	135	1.4	133	140	1.06%
QC3	24	159	2.1	154	163	1.32%

654 Corning

	Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	21	1.87	0.028	1.82	1.92	1.49%
QC2	24	4.10	0.027	4.04	4.16	0.65%
QC3	24	6.54	0.074	6.36	6.65	1.14%

654 Corning

Mission
Level	N	Mean	StdDev	Min	Max	%CV
QC1	21	0.29	0.026	0.24	0.35	8.89%
QC2	24	0.99	0.032	0.90	1.03	3.27%
QC3	24	2.24	0.084	2.05	2.36	3.75%

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Correlation with Corning Reagents

Correlation data were obtained from human serum samples for Na, K, Cl, Ca, and Li.

Serum was first spiked with LiCI to obtain a base Li concentration. .
- Samples were then spiked to yield varying concentrations of each of the measuring o analytes.
. Not all runs were specific for all analytes.
Serum samples were measured each test day on Corning analyzers calibrated with . Mission reagents for 1 run then measured in a comparative run on Corning analyzers calibrated with Corning reagents.

Linear regression analysis was performed using Mission data as the independent X variable and Corning as the dependent Y variable in the equation Y = mX +b

Na
	N	Slope	Intercept	R2	Range
614	50	1.00	1.72	1.00	105 - 187
644	50	1.03	0.25	1.00	100 - 190
654	50	0.97	4.41	1.00	102 - 189

Correlation Data Table 1

K
N	N	Slope	Intercept	R2	Range
614	60	1.01	-0.01	1.00	2.53 - 6.31
644	60	1.04	-0.11	1.00	2.47 - 6.24
654	60	1.07	-0.20	1.00	2.43 - 6.45

N		Slope	Intercept	R2	Range
644	Cl	50	0.97	6.20	1.00	81 - 187
654	Li	30	0.96	0.06	0.99	0.32 - 1.54

Correlations demonstrated slopes of 1.0 and R2 's of ≥ 0.99, which support a claim of . substantial equivalence.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or clothing.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 2 6 2002

Diamond Diagnostics Inc. c/o Ms. Linda Stundtner QA/RA Manager Mission Diagnostics 333 Fiske Street Holliston, MA 01746

K020596 Re:

Trade/Device Name: Mission Diagnostic Calibrating Reagents for Corning 6X4 Electrolyte Analyzers

Regulation Number: 21 CFR 862.1150

Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT Dated: February 19, 2002 Received: February 22 2002

Dear Ms. Stundtner:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), 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 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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

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510(k( Number

Device Name: Mission Diagnostic Calibrating Reagetns for Corning 6X4 Electrolyte Analyzers

Kozo596

Indication For Use:

The products encompassed by this request are intended for in-vitro diagnostics use and for use in r rie products enompassou by the route flow path of the equivalent Corning 6X4 Series Canbrating the Clectrodos and nashing the new changes inch.: Corning Glass, Ciba-Corning, Chiron, and currently Bayer) is the Original Equipment Manufacturer (OEM) of the analyzers and the predicate reagents.

Mission Product	CorningInstrument Usedon
CD-478541AD	Cal-Pak for Corning 614	614
CD-478548AD	Cal Pak for Corning 634	634
CD-473510AD	Cal-Pak for Corning 644	644
CD-473605AD	Cal-Pak for Corning 654	654

Mission reagents are intended to serve as direct replacements to like named products manufactured by Corning (under the label of current owner, Bayer).

The products encompassed are to be handled using normal laboratory precautions.

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

Concurrence of CDRH, Office of the Device Evaluation (ODE)

prescription use ✓

Carol C. Benson for Jean Cooper

ision Sian-

(Optional format 3-10-98)

510(k) Submission for Mission Diagnostics Reagents on Corning 6X4 Electrolyte Analyzers

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.