SIGMA DIAGNOSTICS INFINITY ASTBUN REAGENT, MODEL 51-25, SIGMA DIAGNOSTICS INFINITY AST REAGENT, MODELS 51-100P,51-500P,5 by SIGMA DIAGNOSTICS, INC.

Sigma Diagnostics INFINITY™ AST Reagent is intended for the in vitro quantitative determination of AST (Aspartate Aminotransferase EC2.6.1.1) in human serum and plasma on both automated and manual systems.

Device Description

The Sigma Diagnostics INFINITY AST Reagent is based on the recommendations of the IFCC. The series of reactions involved in the assay system is as follows:

AST present in the sample catalyzes the transfer of the amino group from L-aspartate to 2-oxoglutarate forming oxaloacetate and L-glutamate.
Oxaloacetate in the presence of NADH and Malate dehydrogenase (MDH), is reduced to L-malate. In this reaction NADH is oxidized to NAD. The reaction is monitored by measuring the rate of decrease in absorbance at 340 nm due to the oxidation of NADH to NAD.
Addition of Lactate dehydrogenase (LDH) to the reagent is necessary to achieve rapid and complete reduction of endogenous pyruvate so that it does not interfere with the assay.

AI/ML Overview

The provided text describes the Sigma Diagnostics INFINITY™ AST Reagent, intended for the quantitative determination of AST in human serum and plasma. The study presented is primarily a correlation study to demonstrate substantial equivalence to a previously cleared device, not a typical diagnostic efficacy study with acceptance criteria like sensitivity or specificity.

Here's an analysis based on the provided input:

Acceptance Criteria and Device Performance Study

The primary study presented demonstrates the substantial equivalence of the INFINITY™ AST Reagent to an existing Sigma Diagnostics AST Reagent (Procedure No. 58, K954839) via a correlation study, rather than setting distinct acceptance criteria for diagnostic accuracy metrics.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Substantial Equivalence (Correlation)	Regression equation indicating close agreement with predicate device (slope near 1, intercept near 0).	INFINITY AST = 0.98 (AST 58) + 0.6 (N=126)
Intended Use	For in vitro quantitative determination of AST in human serum and plasma on automated and manual systems.	The device meets this intended use.
Methodology	Based on IFCC recommendations.	The Sigma Diagnostics INFINITY AST Reagent is based on the recommendations of the IFCC.

Explanation of Performance: The regression equation INFINITY AST = 0.98 (AST 58) + 0.6 with N=126 suggests a strong correlation between the new INFINITY AST Reagent and the predicate AST 58 Reagent. A slope of 0.98 is very close to 1, and an intercept of 0.6 is very close to 0, indicating that the new reagent provides results highly consistent with the established predicate device. This is the primary evidence of "performance" for a substantial equivalence claim in this context.

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

Sample Size: N = 126 plasma samples.
Data Provenance: The text does not explicitly state the country of origin. It is a retrospective study, as it involved analyzing a set of samples and comparing results with a previously cleared device.

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

Not Applicable. This is an in vitro diagnostic (IVD) assay where the "ground truth" for the test set is established by the predicate device's measured values, which are chemical concentrations, not interpretations by human experts.

4. Adjudication Method for the Test Set

Not Applicable. As this is a correlation study comparing results of two chemical assays, there is no expert adjudication method used. The comparison is purely quantitative.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This is an in vitro reagent, not a device that involves human readers interpreting cases. Therefore, an MRMC study is not applicable.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, effectively. The study described is a standalone performance assessment of the reagent's ability to measure AST levels. While the measurement process involves laboratory personnel, the performance evaluation itself focuses on the reagent's output against a reference (the predicate device's output), independent of human interpretation or intervention in the diagnostic decision-making process beyond performing the assay.

7. The Type of Ground Truth Used

Predicate device's measured values. The "ground truth" in this context is the AST concentration determined by the previously cleared Sigma Diagnostics AST Reagent, Procedure No. 58 (K954839), which serves as the comparator or reference method for demonstrating equivalence.

8. The Sample Size for the Training Set

Not Applicable. This is a chemical reagent and not a machine learning or AI algorithm that requires a training set. The "design" of the reagent is based on established biochemical principles (IFCC recommendations) rather than data-driven training.

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

Not Applicable. As there is no training set for this type of device, this question is not relevant.

Summary

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SEP 2 8 1999

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

INFINITY™ AST Reagent, Procedure 51-UV

AST is widely distributed with high concentrations in the heart, liver, skeletal muscle, kidney and erythrocytes. Damage or disease to any of these tissues such as myocardial infarction, viral hepatitis, liver necrosis, cirrhosis and muscular dystrophy may result in raised serum levels of AST.'

The Sigma Diagnostics INFINITY AST Reagent is based on the recommendations of the IFCC.2 The series of reactions involved in the assay system is as follows:

AST present in the sample catalyzes the transfer of the amino group from L-aspartate to 1. 2-oxoglutarate forming oxaloacetate and L-glutamate.
Oxaloacetate in the presence of NADH and Malate dehydrogenase (MDH), is reduced to 2. L-malate. In this reaction NADH is oxidized to NAD. The reaction is monitored by measuring the rate of decrease in absorbance at 340 nm due to the oxidation of NADH to NAD.
Addition of Lactate dehydrogenase (LDH) to the reagent is necessary to achieve rapid and 3. complete reduction of endogenous pyruvate so that it does not interfere with the assay.

The Sigma Diagnostics INFINITY™ AST Reagent Kit (Procedure No. 51-uv) is substantially equivalent to, and is the same product as the TRACE Scientific AST (DST) Reagent Kit cleared by FDA as K961114.

Correlation studies to Sigma Diagnostics AST Reagent, Procedure No. 58 (K954839) using plasma samples yielded a regression equation of:

INFINITY AST = 0.98 (AST 58) + 0.6 (N=126)

References

1. Zilva JF, Pannall PR. "Plasma Enzymes in Diagnosis" in Clinical Chemistry in Diagnosis and Treatment. Lloyd-Luke London. 1979:Chap 17:338-9.
1. IFCC Method for L-Aspartate aminotransferase. J Clin Chem Clin Biochem 1986; 24:497-510.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 2 8 1999

William R. Gilbert, Ph.D. Manager, Scientific Affairs Sigma Diagnostics® Clinical Technical Services 545 South Ewing Avenue St. Louis, Missouri 63103

Re: K992801

Trade Name: Infinity™ AST Reagent (Procedure No. 51) Regulatory Class: II Product Code: CIT Dated: August 16, 1999 Received: August 19, 1999

Dear Dr. Gilbert:

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 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). 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 Regulations, 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 Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory 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/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 (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: Sigma Diagnostics INFINITY™ AST Reagent

Indications For Use:

Sean Cooper

(Division Sign-Off) Division of Clinical Laborate L vices 510(k) Number

(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 _

Regulation Number and Section

§ 862.1100 Aspartate amino transferase (AST/SGOT) test system.

(a)
Identification. An aspartate amino transferase (AST/SGOT) test system is a device intended to measure the activity of the enzyme aspartate amino transferase (AST) (also known as a serum glutamic oxaloacetic transferase or SGOT) in serum and plasma. Aspartate amino transferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease.(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.