The Quantimetrix Cardiasure Assayed Controls are intended for use as quality control materials to assess the accuracy and precision of assay procedures for the analytes included in the control.

The Quantimetrix Cardiasure Control is to be used as a quality control material to assess the accuracy and precision of laboratory test methods used to measure the specific serum analytes contained in the control material in order to validate the measurement of these analytes in patient samples.

Device Description

Cardiasure Assayed Controls are supplied in three levels, 3 x 3 mL each level per box and as a Tri-Level pack: 3 vials at 3 mL of each level; the controls are supplied as a ready-to-use frozen liquid, requiring no reconstitution or dilution. They are prepared in a human serum matrix fortified to target levels with human source material and reagent grade chemicals added at different concentrations to achieve the three levels. Sodium Azide has been added as preservative to inhibit microbial growth.

AI/ML Overview

The provided K993723 510(k) Summary describes a quality control material, not a diagnostic device that directly "measures" or "detects" a condition in a patient. Therefore, many of the typical acceptance criteria and study parameters for AI/ML-based diagnostic devices (like sample size for test sets, expert ground truth, MRMC studies, standalone performance, etc.) are not applicable in this context.

This submission focuses on proving the stability and reliable performance of the control material itself, which then allows laboratories to assess the accuracy and precision of their own assay procedures.

Here's an analysis based on the information provided, highlighting the differences:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Cardiasure Assayed Cardiac Markers Control primarily revolve around its stability and the consistency of analyte recovery over time and under different storage conditions.

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Closed Vial Stability (Frozen Storage)	- Claim: 3 years at -10 to -20°C. - Performance Metric: Increase or decrease of >10% of analyte recovery compared to the initial test value ± the highest allowable instrument/reagent imprecision was used as the analyte failure criterion.	- Based on accelerated stability studies. - Control stored at 2 to 8°C for over 60 days to simulate 3 years storage at -10 to -20°C. - Specific passing/failing results not explicitly stated but implied the claim was met. Real-time stability testing is ongoing.
Closed & Opened Vial Stability (Refrigerated Storage)	- Claim: 30 days at 2 - 8°C (for most analytes). - Performance Metric: Analyte recovery (vs. day 0) measured at regular intervals. - Failure Criterion: Same as above (>10% change compared to initial test value ± highest allowable instrument/reagent imprecision).	- Control stored at 2 - 8°C. - Recovery measured up to 35 days for open vial and up to 64 days for closed vial. - Result: "All lots passed the 30 day refrigerated stability for opened/closed vials (with the exception of Tn-I which has a 14 day stability claim)."
Inter-lot Consistency	- Performance Metric: No significant difference in performance or stability across multiple manufacturing lots.	- "Multiple lots of product were tested with no significant difference in performance or stability."
Analyte Value Establishment	- Performance Metric: Assayed values for specific analytes established from interlaboratory data using instrument manufacturers' reagents. Mean values and expected ranges were calculated from multiple instruments and reagent lots.	- This process was performed, indicating the product can provide consistent reference values for laboratory quality control.
Substantial Equivalence to Predicate Device	- Predicate Stability: Liquichek™ Cardiac Markers Control claims 2-year shelf life at -10 to -20°C and 20-day opened/closed vial stability at 2-8°C (with exceptions for Tn-I and T at 10 days).	- The Cardiasure control demonstrated comparable or superior stability claims (3 years frozen, 30 days refrigerated for most analytes).

Study Details for Device Performance

Given that this is a quality control material and not a diagnostic device, the study design will not align with typical diagnostic device studies.

2. Sample size used for the test set and the data provenance:

Test Set: Not applicable in the traditional sense of patient data. The "test set" consisted of multiple lots of the Cardiasure control material itself and specific analytes within those control materials.
Sample Size: Multiple lots of the product were manufactured and tested.
Data Provenance: The studies were conducted internally by Quantimetrix Corporation. This would be considered prospective data for device testing (i.e., new lots were produced and subjected to stability testing). The source matrix (human serum) contains human source antigens and enzymes.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable. The "ground truth" for this device is its inherent chemical stability and the established concentrations of its analytes. This is determined through analytical chemistry techniques and interlaboratory studies, not expert consensus on medical images or patient diagnoses. The stability criteria are based on analytical recovery within defined limits.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

None applicable. Adjudication is typically for resolving discrepancies in expert interpretations of clinical data. Here, the "truth" is objective chemical measurement against predefined stability thresholds.

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 device is a quality control material, not an AI/ML diagnostic system intended for human reader assistance.

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

Not applicable. This is a physical reagent, not an algorithm. Its "performance" is its ability to maintain stable analyte concentrations and to be accurately assayed by laboratory instruments.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for stability was based on analytical recovery of target analytes compared to initial measurements, verified against scientifically established stability models (like the L. Kennon model referenced). The criteria were defined as a percentage change (>10%) relative to the initial value and instrument/reagent imprecision.
The "ground truth" for the assayed values (concentrations) was established through interlaboratory data, meaning multiple laboratories using various instruments and reagent lots performed assays on the control material to determine mean values and expected ranges. This is a form of empirical measurement consensus within the analytical testing community.

8. The sample size for the training set:

Not applicable. This device is not an AI/ML algorithm that requires a "training set."

9. How the ground truth for the training set was established:

Not applicable. As above, no training set for an AI/ML algorithm is involved.

Summary

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K993723

510K Summary

Prepared: October 26, 1999 Submitted by: Establishment Address:

Quantimetrix Corporation 2005 Manhattan Beach Boulevard Redondo Beach CA 90278 Phone: 310/536-0006 FAX: 310/536-9977

Establishment Registration Number: 2020715

Contact Person: Evy K. Johnson, Director Technical Services &OEM Proprietary Name: Cardiasure Assayed Cardiac Markers Control Common Name: Cardiac Markers Control Classification Name: Enzyme Controls (assayed and unassayed) 75 JJT Substantial Equivalence:

The Quantimetrix Cardiasure Control is supplied liquid in three levels and consists of a human serum matrix containing preservatives to which reagent grade chemicals and human source antigens and enzymes have been added at different concentrations to achieve the three levels. Assayed values are determined from interlaboratory data.

The Quantimetrix controls are substantially equivalent to other such controls in general use, such as the Liquichek™M Cardiac Markers Control sold by BioRad Laboratories Inc., which is supplied liquid in three levels as a human serum matrix with human/non-human source constituents and pure chemicals added by the manufacturer.

Description:

Intended Use:

The Quantimetrix Cardiasure Assayed Controls are intended for use as quality control materials to assess the accuracy and precision of assay procedures for the analytes included in the control.

Technological Characteristics Compared to Predicate Devices:

The Quantimetrix control product uses a matrix and constituent formulation similar to the equivalent predicate device listed above: human serum matrix fortified with human source material, reagent grade chemicals and a preservative. The Quantimetrix Control also has similar storage and stability requirements as the predicate device.

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Performance Characteristics:

The closed vial stability claim made for this product is 3 years when stored at -10 to -20° C, based on accelerated stability studies.2 The Cardiasure control was stored at 2 to 8°C for over 60 days to simulate 3 years storage at -10 to -20°C. An increase or decrease of >10% of analyte recovery compared to the initial test value ± the highest allowable instrument/reagent imprecision was used as the analyte failure criterion for determining shelf life. Real time stability testing is ongoing on multiple lots of product.

The closed and opened vial stability claim for this product when stored at 2 - 8° C is 30 days. The Cardiasure Control was stored at 2 - 8° C and the recovery (vs. day 0) was measured in regular intervals up to 35 days for open vial and up to 64 days for closed vial. The product was deemed stable if it met the above recovery criteria.

All lots passed the 30 day refrigerated stability for opened/closed vials (with the exception of Tn-I which has a 14 day stability claim).

Multiple lots of product were tested with no significant difference in performance or stability.

The predicate device, Liquichek™ Cardiac Markers Control, claims a 2 year shelf life for storage at -10°C to -20°C and a 20 day opened/closed vial stability for refrigerated (2-8°C) storage, with exception of Tn-I and T which have are claimed to be stable for 10 days .

Assayed Values

Assay values were established from interlaboratory data using instrument manufacturers' reagents. Mean values and expected ranges for the listed lots of controls were calculated from multiple instruments and reagent lots available at the time of assay.

2 L. Kennon, Stability Prediction Model, Journal of Pharmaceutical Sciences 53:7, 815-818, 1964.

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Image /page/2/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services - VISA. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - VISA" around the perimeter. Inside the circle are three stylized human profiles facing to the right, stacked on top of each other.

NOV 23 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Evy K. Johnson Director, Technical Services & OEM Quantimetrix Corporation 2005 Manhattan Beach Boulevard Redondo Beach, California 90278-1205

Re: K993723 Trade Name: Cardiasure Regulatory Class: I Product Code: JJT Dated: October 26, 1999 Received: November 3, 1999

Dear Ms. Johnson:

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 Sutman

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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Page ( _of

510(k) Number (if known): K993723

Device Name: Cardiasure Cardian Markers Control

Indications For Use:

Indications for Use

The Quantimetrix Cardiasure Control is to be used as a quality control material to assess the accuracy and precision of laboratory test methods used to measure the specific serum analyres contained in the control material in order to validate the measurement of these analytes in patient samples.

Quality Control materials that have known component concentrations are an integral part of diagnostic procedures. Daily monitoring of control values establishes intra- and interlaboratory parameters for accuracy and precision of the test method.

Three levels of control are provided to allow the performance of the test methods to be monitored within the clinically significant ranges.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices K993723
510(k) Number

Prescription Use ✓
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.