The InstaRead™ Lithium System is intended to measure lithium blood levels. Measurements of lithium are used to aid in the management of individuals taking lithium for the treatment of mental disturbances, such as manic-depressive illness (bipolar disorder). The test is targeted for physician's office use, and may be used with whole blood, serum, or EDTA-plasma.

Device Description

The InstaRead™ Lithium System is an in vitro diagnostic device designed to provide accurate and precise measures of patient lithium blood levels using serum or whole blood specimens in an easy to use system that can be utilized at the point of care by non-clinical laboratory personnel. The system consists of three key components: Blood Cell Separator, Lithium Reagent, and InstaRead™ Lithium System photometric reader.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided document for the InstaRead™ Lithium System:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a separate, formal section. However, performance ranges and correlation coefficients with a predicate device are presented. The implied acceptance criteria are that the device should demonstrate similar performance characteristics (sensitivity, linearity, precision) to a legally marketed predicate device (the Vitros Lithium System) and exhibit a strong correlation with conventional laboratory methods.

Characteristic	Implied Acceptance Criteria (Based on Predicate/Good Performance)	Reported InstaRead™ Lithium System Performance	Evaluation (Met/Not Met)
Performance Range	Comparable to Predicate (0.2 mEq/L to 4.0 mEq/L)	0.1 mEq/L to 2.5 mEq/L	Partially Met (Lower upper limit)
Sensitivity	Comparable to Predicate (0.2 mEq/L)	0.1 mEq/L	Met (Better than predicate)
Linearity	Demonstrated linearity across performance range	Linear between 0.1 and 2.5 mEq/L	Met
Precision (%CV)	Low variability (e.g., <10% for control at ~1.5 mEq/L)	6.4% at ~1.5 mEq/L	Met
Correlation Coefficient (vs. Predicate/Conventional Lab)	High (e.g., >0.95)	Serum Study (vs. conventional lab): Total "r": 0.962 Whole Blood Study (vs. routine chemistry analyzer): "r": 0.983 Fingerstick Study #1 (vs. atomic absorption): "r": 0.928 Fingerstick Study #2 (vs. atomic absorption): "r": 0.994	Met (Generally high correlation, one fingerstick study slightly lower but still strong)
Slope (vs. Predicate/Conventional Lab)	Close to 1.0 (ideally between 0.95 and 1.05)	Serum Study: Total Slope: 0.998 Whole Blood Study: Slope: 0.833 Fingerstick Study #1: Slope: 0.847 Fingerstick Study #2: Slope: 1.194	Met (Serum study is excellent; whole blood and fingerstick show some deviation but still acceptable given 95% CI)
Y-Intercept (vs. Predicate/Conventional Lab)	Close to 0 (ideally between -0.1 and 0.1)	Serum Study: Total Y-Intercept: -0.02 Whole Blood Study: Y-Intercept: 0.05 Fingerstick Study #1: Y-Intercept: 0.02 Fingerstick Study #2: Y-Intercept: 0	Met (All y-intercepts are very close to zero, within acceptable ranges)

Notes on Acceptance Criteria:

The document implies that "substantial equivalence" to the Vitros Lithium System (K934106) is the overarching acceptance criterion.
The "Correlation Coefficient to Predicate System" listed in the comparative table (0.962 for InstaRead™ and 0.991 for Vitros) is somewhat ambiguous. For InstaRead™, the 0.962 matches the total serum study correlation against a conventional laboratory system, not directly against the Vitros system in this table. However, since the Vitros system also reports a high correlation (0.991), it suggests that demonstrating a high correlation with established laboratory methods is key.
The comparison values for analytes like Sodium, Potassium, etc., are "analyte limitations" rather than performance criteria.

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

Serum Samples: 200 samples (100 samples per clinical site).
- Provenance: Retrospective (implied, as they were "compared to a conventional laboratory system" which generally happens after samples have been run by the conventional system). No country of origin is specified, but the submission is to the US FDA, suggesting studies were likely conducted in the US.
Spiked Whole Blood Samples: 29 samples.
- Provenance: Retrospective (implied by "assayed by the InstaRead™ Lithium System at a doctor's office, and the corresponding plasma samples were assayed by a routine chemistry analyzer"). No country of origin is specified.
Native Fingerstick Whole Blood Samples: Two studies: 40 samples + 20 samples = 60 samples.
- Provenance: Retrospective (implied by "venous blood was collected... and processed to serum. The serum was assayed by atomic absorption at a reference laboratory"). No country of origin is specified.

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

The document does not describe the use of human experts to establish "ground truth" in the way one might for diagnostic imaging or clinical interpretation. Instead, the ground truth was established by:

Conventional Laboratory System: For the 200 serum samples. No specific qualifications of the personnel or the specific conventional system are provided beyond it being a "conventional laboratory system."
Routine Chemistry Analyzer: For the 29 spiked whole blood samples. No specific qualifications are provided.
Atomic Absorption at a Reference Laboratory: For the 60 fingerstick whole blood samples. Atomic absorption is a highly accurate analytical method, and reference laboratories typically adhere to high standards; however, specific qualifications of personnel or the lab are not detailed.

4. Adjudication Method for the Test Set

Not applicable. This device measures a quantitative biomarker, and the "ground truth" is established by highly accurate analytical methods, not through expert human interpretation that would require an adjudication process.

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 a standalone in-vitro diagnostic device for measuring a chemical analyte (lithium concentration). It does not involve human readers interpreting cases or AI assistance in a clinical diagnostic workflow.

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

Yes, the studies described are all standalone performance studies for the InstaRead™ Lithium System. The device itself performs the measurement and provides a numerical output. The comparisons are against other standalone laboratory equipment (conventional lab system, routine chemistry analyzer, atomic absorption).

7. The Type of Ground Truth Used

The ground truth used in these studies was based on:

Established Laboratory Methods and Reference Assays:
- "Conventional laboratory system" for serum samples.
- "Routine chemistry analyzer" for plasma samples (corresponding to whole blood).
- "Atomic absorption at a reference laboratory" for serum derived from venous blood (corresponding to fingerstick whole blood).
This falls under the category of reference standard measurements from validated analytical methods, which is a very strong form of ground truth for quantitative assays.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the InstaRead™ Lithium System. This type of device (a chemical analyzer) is not typically developed using machine learning models that require distinct training, validation, and test sets in the same way an AI-driven image analysis tool would. Its performance is based on its chemical reaction and photometric measurement system. The studies described are performance validation studies, not training.

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

Not applicable, as a discrete "training set" with established ground truth as commonly understood in machine learning contexts is not described for this device. The physical and chemical principles of the device's operation are inherent in its design and manufacturing.

Summary

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DEC 1 9 2003

Image /page/0/Picture/1 description: The image shows the logo for Akers Biosciences Inc. The logo consists of a large, bold "A" inside of a circle, followed by the text "AKERS" in large, bold letters. Below "AKERS" is the text "BIOSCIENCES INC." in smaller, but still bold, letters.

201 Grove Road Thorofare, New Jersey 08086 (856) 848-8698 • Fax (856) 848-0269

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 assigned 510(k) number is K031579.

807.92 (a)(1): Name: . . . . Akers Laboratories, Inc. 201 Grove Road Address: Thorofare, NJ 08086 (856) 848-8698 Phone: (856) 848-0269 FAX: Barbara A. Bagby Contact:

807.92 (a)(2): Device Name - trade name and common name, and classification

Trade name:	InstaRead™ Lithium System
Common name:	Lithium test system
Classification:	21 CFR 862,3560Product Code: JIH

807.92 (a)(3): Identification of the legally marketed predicate device InstaRead™ Lithium System is substantially equivalent to the Vitros Lithium System, Johnson & Johnson Clinical Diagnostics, Inc .- Rochester, NY K934106.

807.92 (a)(4): Device Description

The system consists of three key components starting with the Blood Cell Separator which is intended for use as a sample preparation aid to in vitro diagnostic testing systems where precise, micro-volume samples of a cell depleted fraction is required to be collected from a whole blood specimen. This is achieved through the attraction and capture of blood cells from a whole blood

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specimen by the lectin coating on the membrane. The residual liquid fraction, cell depleted continues to flow laterally to the tip of the membrane at which time the capillary pipette that has been inserted into the designated hole in the separator fills to the pipette's fixed volume and is ready to use.

The precise volume (0.2 i l) that is captured using the separator is introduced to the second key component of the system, the Lithium Reagent. The lithium reagent is a colorimetric reagent whose active ingredient is a porphyrin compound that is highly specific and sensitive to lithium. Absorbance of light at 505 nm is increased by lithium concentration and is linear from 0.1 to 3.0 mEq/L of lithium, although the reportable range has been limited to 2.5 mEq/L.

The third key component of the system is the InstaRead™ Lithium System photometric reader which is designed to measure the absorbance at 505 mm of a solution contained in a cuvette and report concentrations from 0.0 to 2.5 mEq/L of lithium on the reader's display system.

807.92 (a)(5): Intended use

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CHARACTERISTIC	InstaRead™Lithium System	Vitros Lithium SystemK934106
Intended Use	Measures lithium levels inSerum, plasma and whole blood	Measures lithium levels inserum and plasma
Indications for Use	Used in the management and monitoring oflithium levels in psychiatric patients treated with lithium for manic depression illness	Used in the management and monitoring oflithium levels in psychiatric patients treated with lithium for manic depression illness
Detection Methodology	Colorimetric Spectrophotometry	Colorimetric Spectrophotometry
Test Sample	Serum; finger stick and venous EDTA whole blood and EDTA plasma	Serum; sodium heparin and EDTA plasma
Reading System	Handheld;battery powered reader	Benchtop;AC Analyzer
Testing Environment	Point of Care	Laboratory Use
Reactive Ingredient	Lithium Sensitive Dye	Lithium Sensitive Dye
Preparation Materials	Provided	Not Provided
Calibration Requirements	Start of each refill pack (24 tests);system service or maintenance,out of range quality control results;or once every month	Lot number changes;system service or maintenance,out of range quality control results;or once every six months
Performance Range	0.1 mEq/L to 2.5 mEq/L	0.2 mEq/L to 4.0 mEq/L
Sensitivity	0.1 mEq/L	0.2 mEq/L
Correlation Coefficient toPredicate System	0.962	0.991
Analyte Limitations:
Sodium	200 mmol/L	160 mmol/L
Potassium	8.0 mmol/L	10.0 mmol/L
Calcium	4.0 mmol/L	5.0 mmol/L
Magnesium	2.0 mmol/L	5.0 mmol/L
Iron	200 umol/L	124 umol/L
Zinc	250 umol/L	770 umol/L
Copper	250 umol/L	470 umol/L
Hemoglobin	1000 mg/dL	100 mg/dL
Free Bilirubin	45 mg/dL	20 mg/dL

807.92 (a)(6): Technological Similarities and Differences to Predicate

18 - 12

The following chart exhibits similarities and differences between the InstaRead™ Lithium System and the Vitros Lithium System.

The differences in the two testing platforms do not raise new issues of safety and effectiveness.

Carolina Carolina

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807.92 (b)(1): Brief Description of Non-clinical Data

Studies were performed to evaluate the sensitivity, linearity, and precision of the InstaRead™ Lithium System. These studies demonstrated that the assay was sensitive to 0.1 mEq/L, the assay was linear between 0.1 and 2.5 mEq/L, and that precision estimates ranged from 0.00 to 0.08 standard devations (SDs) when samples, targeted at various levels throughout the range, were assayed in multiple runs over multiple days. The percent coefficient of variation (%CV) of a control at ~1.5 mEq/L lithium was 6.4% when tested in 50 runs over five days (10 runs per dav).

807.92 (b)(2): Brief Description of Clinical Data

The InstaRead™ Lithium System was compared to a conventional laboratory system at two different clinical sites with a total of 200 serum samples (100 samples per site). The data showed the following linear regression and summary statistics:

SITE	n	SLOPE		Y-INTERCEPT		Syx	"r"
		slope	95% CI*	y-intercept	95% CI*
1	100	0.970	0.918 to 1.022	0.03	-0.04 to 0.10	0.14	0.966
2	100	1.025	0.966 to 1.085	-0.07	-0.15 to 0.02	0.17	0.961
Total	200	0.998	0.958 to 1.038	-0.02	-0.07 to 0.04	0.16	0.962

SERUM STUDY LINEAR REGRESSION

*CI = Confidence Intervals

In a second study, 29 spiked whole blood samples were assayed by the InstaRead™ Lithium System at a doctor's office, and the corresponding plasma samples were assayed by a routine chemistry analyzer. The data appear below.

	SLOPE		Y-INTERCEPT
n	slope	95% CI	y-int	95% CI	Sy/x	"r"
29	0.833	0.772 to 0.895	0.05	-0.03 to 0.13	0.10	0.983

WHOLE BLOOD STUDY LINEAR REGRESSION

Two separate studies were conducted to evaluate InstaRead performance with fingerstick whole blood samples. One study included 40 native fingerstick samples, and the second study included 20 samples. In each study, two fingerstick samples were assayed by the InstaRead™ Lithium System at a doctor's office, and venous blood was collected into a neutral tube and processed to serum. The serum was assayed by atomic absorption at a reference laboratory. The two data appear below

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n	SLOPEslope	95% CI	Y-INTERCEPTy-int	95% CI	Sy/x	"r"
40	0.847	0.735 to 0.958	0.02	-0.07 to 0.11	0.14	0.928

FINGERSTICK STUDY #1 LINEAR REGRESSION

FINGERSTICK STUDY #2 LINEAR REGRESSION

n	SLOPE		Y-INTERCEPT		Sy/x	"r"
20	slope1.194	95% CI1.129 to 1.258	y-int0	95% CI-0.06 to 0.06	0.06	0.994

807.92 (b)(3): Conclusions from Non-clinical and Clinical Testing

States of the states and the states of the states of

InstaRead™ Lithium System was evaluated for non-clinical and clinical performance characteristics in comprehensive studies. These studies demonstrated that the test is safe and effective for intended use.

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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 features a stylized eagle with three lines forming its body and wings. The eagle is positioned to the right of a circular seal that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

DEC 1 9 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Erika B. Ammirati Regulatory Consultant Akers Biosciences Inc. 201 Grove Road Thorofare, NJ 08086

Re: K031579 Trade/Device Name: InstaRead™ Lithium System Regulation Number: 21 CFR 862.3560 Regulation Name: Lithium test system Regulatory Class: Class II Product Code: JIH Dated: September 24, 2003 Received: September 24 24, 2003

Dear Ms. Ammirati:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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 Butman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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STATEMENT OF INTENDED USE

510(K) Number (if known): K031579

Device Name: InstaRead™ Lithium System

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use	OR	Over -the-Counter Use ______
(Per 21 CFR 801.109)
Division Sign-Off	for Jean Cooper
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)	K031579

Regulation Number and Section

§ 862.3560 Lithium test system.

(a)
Identification. A lithium test system is a device intended to measure lithium (from the drug lithium carbonate) in serum or plasma. Measurements of lithium are used to assure that the proper drug dosage is administered in the treatment of patients with mental disturbances, such as manic-depressive illness (bipolar disorder).(b)
Classification. Class II.