MULTIQUANT (R) QUANTITATIVE MYOGLOBIN TEST by SPECTRAL DIAGNOSTICS, INC.

The Multiquant® Quantitative Myoglobin Test is intended for use for as an in vitro diagnostic product to measure by immunochemical techniques the myoglobin ( an oxygen storage protein found in muscle) in serum and plasma. Measurement of myoglobin aids in the rapid diagnosis of heart disease.

Device Description

The Spectral Diagnostics Multiquant® Quantitative Myoglobin Test is an automated latex immunoturbidometric method. The test utilizes a monoclonal antibody and a polyclonal antibody each covalently bound to polystyrenesupercarboxylated latex particles. When serum or plasma and assay buffer are combined with the latex particles, myoglobin in the specimen crosslinks adjacent latex beads and produces an increase in the turbidity of the solution. The turbidity, measured at 600nm, is proportional to the concentration of myoglobin present in the serum or plasma.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided document for the Spectral Diagnostics Multiquant® Quantitative Myoglobin Test:

Acceptance Criteria and Device Performance for Spectral Diagnostics Multiquant® Quantitative Myoglobin Test

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Method Correlation	Correlation coefficient (r) with predicate device	0.99
Regression Equation (vs. predicate)	Slope and Y-intercept comparable to predicate	Multiquant® = 1.04(Stratus®) + 0.0
Precision (Within Run)	Not explicitly stated as a numerical criterion for acceptance, but demonstrated for specific concentrations.	3.59% for 32.08 mg/mL myoglobin, 2.03% for 288.72 mg/mL myoglobin
Precision (Between Run)	Not explicitly stated as a numerical criterion for acceptance, but demonstrated for specific concentrations.	6.48% for 32.08 mg/mL myoglobin, 2.74% for 288.72 mg/mL myoglobin

Rationale for Acceptance Criteria: The primary acceptance criterion for substantial equivalence was method correlation with a legally marketed predicate device (Dade-Behring Stratus® Myoglobin Fluorometric Assay). A correlation coefficient of 0.99, indicating a very strong linear relationship, along with a regression equation close to y=x (or a slope near 1 and y-intercept near 0), demonstrates that the new device performs comparably to the predicate. Precision data supports the reliability and reproducibility of the device.

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

Sample Size: 172 serum samples (N = 172).
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in vitro diagnostic product, it is most likely that the samples were collected in a clinical setting (e.g., hospital laboratory) and were retrospective (pre-existing samples) or collected via a prospective study for the purpose of this validation. No specific country of origin is mentioned, but the manufacturer is Canadian (Spectral Diagnostics Inc. 135-2 The West Mall Toronto, Ontario Canada M9C 1C2) and the regulatory body is the US FDA, so the study could have been conducted in either country or internationally.

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

This information is not applicable to this type of device and study. For in vitro diagnostic assays like the Multiquant® Quantitative Myoglobin Test, the "ground truth" for the test set is established by testing the samples with a predicate device (the Dade-Behring Stratus® Myoglobin Fluorometric Assay). The performance of the new device is then compared against the results generated by this established predicate method. No human experts are used to interpret the results and establish a "ground truth" in the way they would for image-based diagnostic aids.

4. Adjudication Method for the Test Set:

Not applicable. As described above, the ground truth is established by the predicate device's measurement. There is no subjective human interpretation requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No. An MRMC study is not applicable to this type of in vitro diagnostic device. MRMC studies are typically used to assess human reader performance, often in the context of imaging diagnostics where radiologists interpret images. This device measures a biomarker concentration, which is an objective numerical result, not subject to human interpretation in the same way. Therefore, there is no "human reader" component to improve.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:

Yes. The study described (method correlation and precision) represents the standalone performance of the Spectral Diagnostics Multiquant® Quantitative Myoglobin Test. It evaluates the device's ability to accurately and precisely measure myoglobin concentrations in serum/plasma samples, independently of human interpretation. The output is a quantitative value, not a diagnosis requiring human augmentation.

7. Type of Ground Truth Used:

Predicate Device Results (Comparative Ground Truth): The "ground truth" for the performance evaluation of the Multiquant® test was the results obtained from the Dade-Behring Stratus® Myoglobin Fluorometric Assay. The study aimed to demonstrate substantial equivalence by showing that the new device's measurements correlated highly with those of an already legally marketed and accepted device.

8. Sample Size for the Training Set:

Not explicitly stated/Likely not applicable in the classical sense. For an immunoassay like this, there isn't a "training set" in the machine learning sense that would be used to develop an algorithm. The "training" of such a device primarily involves optimizing the chemical reagents, reaction conditions, and calibration curve during the product development phase. This optimization process would typically involve numerous experiments and testing of different concentrations of myoglobin, but not a distinct "training set" of patient samples in the way that an AI algorithm has a training dataset. The 172 validation samples would be its primary performance assessment.

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

Not explicitly stated/Likely not applicable as described above. Since there isn't a classical training set for a machine learning algorithm, the concept of establishing "ground truth" for it is not directly applicable. The "ground truth" for calibration and optimization during development would originate from known concentrations of myoglobin standards.

Summary

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OCT 7 1998

L982679

Spectral Diagnostics Inc. Multiquant® Quantitative Myoglobin Test 510(k) Notification

PREMARKET NOTIFICATION 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

Myoglobin is an oxygen-binding heme protein with a molecular weight of 17,800 daltons. normally found in cardiac and skeletal tissue which serves as an oxygen-storing pigment necessary for a high level of oxidative phosphorylation. It constitutes about 2% of the total muscle protein and is located in the cell. Cell injury or death during acute myocardial infarction (AMI) has been shown to release myoglobin into the blood. Blood myoglobin reaches the upper limit of normal approximately 2-3 hours after the onset of symptoms. The concentration of myoglobin has been shown to peak at 9-12 hours and to return to normal within 24-36 hours after an AMI.1-2 A number of reports have been published detailing the clinical utility of myoglobin in the early diagnosis and monitoring of AMI.36

The safety and effectiveness of the Spectral Diagnostics Multiquant® Quantitative Myoglobin Test is demonstrated by its substantial equivalency to Dade-Behring Stratus® Myoglobin Fluorometric Assay. Both tests for myoglobin are used to measure myoglobin in serum and plasma and both use immochemical technologies. In a methods correlation against the Stratus® Myoglobin Fluorometric Assay the correlation coefficient was 0.99 and a regression equation of Multiquant® = 1.04(Stratus ) + 0.0, N= 172, r = 0.99 , range = 7.6 to 496.3 ng/mL was obtained with serum samples. Within run precision and between run precision were 3.59% and 6.48% respectively for a sample containing 32.08 mg/mL myoglobin and 2.03% and 2.74% respectively for a sample containing 288.72 mg/mL.

References

Chapelle, J.P. et al., Serum myoglobin determinations in the assessment of acute myocardial infarction. Eur.Heart Journal. 3:122 (1982)
Kagen, L. et al., Myoglobinemia following myocardial infarction. Am.J.Med. 58:177 (1975)
Ohman, E.M. et al., Early detection of acute myocardial infarction: Additional diagnostic information from serum concentrations of myoglobin in patients without ST elevation. Br.Heart J. 63:335 (1990)
Mair, J. et al., Rapid diagnosis of myocardial infarction by immunoturbidimetric myoglobin measurement. Lancet 337:1343 (1991)
Tucker, J.F., et al., Value of serial myoglobin levels in the early diagnosis of patients admitted for acute myocardial infarction, Ann.Emerg.Med. 24:704 (1994)
Gibler, W.B., et al. Myoglobin as an early indicator of acute myocardial infarction. Ann.Emerg.Med. 16:851 (1987)

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Image /page/1/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 stripes forming its wing. The eagle is positioned within a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the circumference of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 7 1998

Joseph Laurino, Ph.D. Director of Operations Spectral Diagnostics Inc. 135-2 The West Mall Toronto, Ontario Canada M9C 1C2

Re : K982679 Multiquant® Quantitative Myoglobin Test Regulatory Class: II Product Code: DDR Dated: July 29, 1998 Received: July 31, 1998

Dear Dr. Laurino:

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 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A 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 regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements 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 regulations.

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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 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" (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 Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health

Enclosure

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Spectral Diagnostics Inc. Multiquant® Quantitative Myoglobin Test 510(k) Notification

K982679

510(k) Number (if Known) : Not Known at this time

Device Name : Multiquant® Quantitative Myoglobin Test

Indications for Use:

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

Image /page/3/Figure/7 description: The image shows a form titled "Concurrence of CDRH, Office of Device Evaluation (ODE)". The form has two options: "Prescription Use (Per 21 CFR 801.109)" and "Over-The Counter Use (Optional Format 1-2-96)". The prescription use option has been selected. There is a signature at the bottom of the form labeled "(Division Sign-Off)" and "Division of Clinical Laboratory Devices".

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K982679

Regulation Number and Section

§ 866.5680 Myoglobin immunological test system.

(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).