For in vitro diagnostic use with the CARESIDE Analyzer to measure LDH activity from anti-coagulated whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with certain liver diseases, heart diseases, and tumors of the lung, kidneys, and liver.

Device Description

CARESIDE LDH cartridges are used with the CARESIDE, Inc. CARESIDE Analyzer to measure LDH activity in anti-coagulated whole blood, serum or plasma specimens. The CARESIDE LDH cartridge, a single use disposable in vitro diagnostic test cartridge, delivers a measured volume of serum or plasma to a dry film to initiate the measurement of LDH activity. The patented film cartridge contains all reagents necessary to measure LDH activity.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the CARESIDE LDH device, based on the provided text:

Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implicit, based on predicate)	Reported CARESIDE LDH Performance	Predicate Device (Vitros LDH DT Slides) Performance
Detection Limit	Not explicitly stated, implied to be comparable to predicate or better	50 U/L	100 U/L
Reportable Range	Not explicitly stated, implied to be clinically useful	50 - 650 U/L	100 - 1750 U/L
Recovery	Not explicitly stated (predicate data not available)	Mean: 103%	Not available
Linearity	Acceptable slope and correlation coefficient	Yielded slope and correlation coefficient within acceptable limits	Not available
Interference	No significant interference at specified concentrations	No significant interference observed at tested concentrations of interferents: Ascorbic Acid: 20 mg/dL, Bilirubin: 20 mg/dL, Triglycerides: 3000 mg/dL	Not available
Precision (Total CV)	Not explicitly stated, implied to be clinically acceptable	335 U/L, 7.2%	649 U/L, 2.9%
Relative Accuracy	High correlation and minimal bias to a reference method (BM/Hitachi 902)	Careside = 0.97 (BM/Hitachi 902) + 9.1 U/L, r = 0.99	Not available

Study Information

Sample sizes used for the test set and data provenance:
- The document does not explicitly state the sample size for the test set used for the performance characteristics reported (Detection Limit, Reportable Range, Recovery, Linearity, Interference, Precision, Relative Accuracy).
- The document does not explicitly state the data provenance (e.g., country of origin, retrospective or prospective) for the test set. It can be inferred that the testing was performed by the manufacturer, CARESIDE, Inc., prior to submission.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. The performance characteristics seem to be based on laboratory measurements against reference instruments or calibrated standards rather than expert consensus on diagnostic images or clinical outcomes.
Adjudication method for the test set:
- This information is not applicable or provided. The performance assessment for this in vitro diagnostic device does not involve adjudication by multiple experts in the way clinical diagnostic imaging studies might.
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:
- No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging or interpretation tool for human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the reported performance characteristics (Detection Limit, Reportable Range, Recovery, Linearity, Interference, Precision, Relative Accuracy) likely represent the standalone performance of the CARESIDE LDH system (cartridge + analyzer) as an in vitro diagnostic test. There is no human-in-the-loop component in the analytical measurement itself; the analyzer quantifies LDH activity.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the analytical performance appears to be established through:
  - Reference Methods/Instruments: For relative accuracy, it was compared to a "BM/Hitachi 902" analyzer.
  - Calibrated Standards: Linearity and recovery assays typically use samples with known, precisely measured concentrations.
  - Controlled Samples: Interference studies use samples spiked with known interferents at specific concentrations.
The sample size for the training set:
- The document does not directly mention a "training set" in the context of an AI/algorithm. For an in vitro diagnostic device like this, method development and calibration would be performed using various samples, but these are not typically referred to as a "training set" in the machine learning sense. The device uses lot-specific standard curves, which are established during manufacturing.
How the ground truth for the training set was established:
- Not applicable as there isn't a "training set" for an AI algorithm. For the device's internal calibration, the instrument uses "lot-specific standard curve" information, which is "bar-coded on each cartridge." This implies that during the manufacturing of each batch (lot) of cartridges, their performance is characterized against known standards to create a unique calibration curve that ensures accurate readings for that specific lot.

Summary

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Page 1

3 200-JUL

May 14, 2002
K020484

510(K) SUMMARY: CARESIDE LDH SAFETY AND EFFECTIVENESS

I. Applicant Information

Applicant Name A. B. Applicant/Manufacturer Address
Telephone Number

CARESIDE, Inc.

6100 Bristol Parkway Culver City, CA 90230 310-338-6767 Renate A. MacLaren, Ph.D. 310-670-6986 rmaclaren@CARESIDE.com May 14, 2002

G. Date 510(k) Summary prepared
Contact Person

e-Mail Address

FAX Number

II. Device Information

A. Device Name (Trade) CARESIDE LDH Device Name B. LDH test system (Classification) C. Device Classification Clinical chemistry panel LDH test system Regulation Number: 21 CFR 862.1440 Regulatory Class II Classification Number: 75CFH D. Special controls and None applicable performance standards

III. Substantial Equivalence Claim

A. General Equivalency Claim

The ability to monitor analyte-specific biochemical reactions in dry film and other formats is widely recognized and has gained widespread acceptance for use in chemistry assays.

LDH in vitro diagnostic products, in both dry film and other formats, are legally marketed in the United States.

B. Specific equivalency claim
The CARESIDE LDH test is substantially equivalent in principle, intended use, and clinical performance to the currently marketed Vitros slides for the quantitative measurement of LDH on the Vitros DT 60 II.

Name of Predicate Device:	Johnson and Johnson's (formerly Eastman Kodak, Inc.) Vitros LDH DT Slides forJohnson and Johnson's Vitros DT 60(formerly Eastman Kodak's DT 60 II).
Predicate Device 510K number:	K912844/A
Product Code:	75CFJ

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IV. Device Description

Explanation of Device Function A.

The activity of the CARESIDE LDH test measures LDH activity in the direction of the conversion of lactate to pyruvate. Some other LDH tests measure the activity of the enzyme in the direction of the conversion of pyruvate to lactate. The two different methods yield clinically equivalent results when interpreted with respect to their own reference ranges although the results are different quantitatively.

Each CARESIDE LDH cartridge consists of an LDH-specific multi-layer reagent film mounted in a plastic base with a hinged lid. The user introduces the specimen into the cartridge sample deposition well, closes the lid and inserts the cartridge into the CARESIDE Analyzer.

Once loaded, the CARESIDE Analyzer scans the cartridge barcode, brings the cartridge and the contained specimen to 37℃, and spins the cartridge to move the sample from the sample deposition well into the cartridge channels and chambers. Approximately 8.5 microliters of sample remains in the metering passage. Any excess sample flows into an overflow well.

The sample is automatically dispensed onto the multi-layer reagent film. The spreading and substrate layer distributes the LDH containing specimen uniformly. The sample moves through a reagent layer where the NADH formed in the LDH catalyzed reaction of lactate and NAD reacts with nitrotetrazolium blue (NTB) in a diaphorase catalyzed reaction to produce a bluish formazan dve. The rate of change of the dye's color intensity, as measured by the amount of reflected light at 570 nanometers, directly relates to the specimen LDH activity.

Test Reaction Sequence:
L-Lactate + NAD+ -------------------------------------------------------------------------------------------------------------------------------------------------------------
NTB + NADH -------------------------------------------------------------------------------------------------------------------------------------------------------------------

As the cartridges spin, a photodiode measures reflectance of light emitted by a wavelength-specific light emitting diode (LED) over a fixed time period. The instrument uses the reflectance measurements and the lot-specific standard curve to calculate LDH activity.

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B. Test Summary

Lactate dehydrogenase (LDH) is distributed very widely in the body and is found in the in very high activities in the cytoplasm of cells in the heart, liver, kidney, and skeletal muscle, and in lesser amounts in lung, smooth muscle, erythrocytes, brain and pancreas. Because activities of LDH are much higher in tissues than in plasma, injury to tissue, with accompanying leakage of the cytoplasm into the peripheral blood, can increase the blood LDH dramatically. At least five forms of LDH are separable by electrophoresis. The predominant form in the blood varies with the tissue of origin, and therefore, LDH sub-typing may have diagnostic value.

Above-normal LDH activities in blood (> 220 U/L) are seen in several hematologic, neoplastic, cardiac, hepatic, skeletomuscular, and renal diseases. Very high elevations (> 500 U/L) of LDH activity have been seen in megaloblastic anemia, extensive carcinomatosis, viral hepatitis, shock, hypoxia, and extreme hyperthermia. Somewhat lower elevations (>300 U/L) occur after myocardial or pulmonary infarction, leukemia, and hemolytic anemia. Moderate elevations occur in cirrhosis, obstructive jaundice, and neoplastic diseases. Thus, an elevated LDH activity is only a nonspecific finding.

V. Intended Use

Intended Use A.
The CARESIDE LDH cartridge is intended for in vitro diagnostic use in conjunction with the CARESIDE Analyzer to quantitatively measure LDH activity in anti-coagulated whole blood, serum or plasma.
B. Indications for Use
For in vitro diagnostic use with the CARESIDE Analyzer to measure LDH activity from anti-coagulated whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with certain liver diseases, heart diseases, and tumors of the lung, kidneys, and liver.

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Technological Characteristics VI.

Similarities A.

	CARESIDE LDH	Vitros LDH DT Slides
Intended Use	For in vitro diagnostic use	Same
Indications	Primarily to aid in the diagnosisand treatment of patients withcertain liver diseases, heart disease,and tumors of the lung, kidneys,and liver.	Same
Measurement	Quantitative	Quantitative
MethodPrinciple	Dry film based reflectancemeasurement of NAD reduction toNADH consequent to conversion oflactate to pyruvate.	Dry film based reflectancemeasurement of NADH oxidation toNAD consequent to conversion ofpyruvate to lactate.
SpecimenDilution	Not required	Not required
Materials	Lithium lactate, NAD+,nitrotetrazolium blue, anddiaphorase	NADH and sodium pyruvate
Detector	Reflectance (570 nm)	Reflectance (340 nm)
Test time	Approx. 4-minute warm-up (on-board) plus 4 minute test time.	15 minutes slide warm-up (off-line)plus 5 minutes test time.
Sample Type	Anti-coagulated wholeblood,serum or plasma	Serum or plasma
SpecimenVolume	8.5 μl test volume(90 ± 10 μl applied volume)	10 μl
Calibration	Calibration information bar-codedon each cartridge. Calibrationinformation may change with eachlot.	Run Vitros DT II calibratorswhenever a new slide lot is used orwhen necessary.
QualityControl	2 levels	2 levels
ReportingUnits	U/L	U/L
ReactionTemp.	37 °C	37 °C
	CARESIDE LDH	Vitros LDH DT Slides
Specimen Pre-treatment	Not Required	Not Required
ReportableRange	50 to 650 U/L	100 to 1750 U/L
Accuratepipetting	Not required	Required
Reagent pre-warming	Not required	Required

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B. Differences

C. Comparative Performance Characteristics

	CARESIDE LDH	Vitros LDH DT Slides
Detection limit	50 U/L	100 U/L
Reportable range	50 - 650 U/L	100 - 1750 U/L
Recovery (Mean)	103%	Not available
Linearity	Linearity by dilution yielded slope and correlation coefficient within acceptable limits
Interference	No significant interference observed at tested concentration of interferent:Ascorbic Acid, 20 mg/dLBilirubin, 20 mg/dLTriglycerides 3000 mg/dL
Precision	Total CV, 335 U/L, 7.2%	Total CV, 649 U/L, 2.9%
Rel. Accuracy	Careside = 0.97 (BM/Hitachi 902) + 9.1 U/L r = 0.99

D. Conclusion

The nonclinical and clinical data provided demonstrate that the CARESIDE LDH product is substantially equivalent to the legally marketed predicate device.

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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 consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the top half. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three stylized human profiles facing to the right.

JUL 3 2002 Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Renate A. MacLauren, Ph.D. Clinical Affairs Manager Careside, Inc. 6100 Bristol Parkway Culver City, CA 90230

K020484 Re:

Trade/Device Name: Careside LDH Regulation Number: 21 CFR 862.1440 Regulation Name: Lactate dehydrogenase test system Regulatory Class: Class II Product Code: CFH Dated: May 15, 2002 Received: May 16, 2002

Dear Dr. MacLauren:

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 1 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/cdrb/dsma/dsmamain.html".

Sincerely yours.

Steven Butman

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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INDICATIONS FOR USE

510(k) Number:

<020484

Device Name:

CARESIDE LDH

Indications for use: For in vitro diagnostic use with the CARESIDE Analyzer to measure LDH activity from anti-coagulated whole blood, serum or plasma specimens to aid in the diagnosis and treatment of patients with certain liver diseases, heart diseases, and tumors of the lung, kidneys, and liver.

Han Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K020484

(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

§ 862.1440 Lactate dehydrogenase test system.

(a)
Identification. A lactate dehydrogenase test system is a device intended to measure the activity of the enzyme lactate dehydrogenase in serum. Lactate dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction, and tumors of the lung or kidneys.(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 § 862.9.