Assayed control material for in vitro diagnostic use to monitor the precision and accuracy of immunochemistry test procedures for the ADVIA Centaur® andACS:180® Systems.

Device Description

The Ligand Plus 1, 2, 3 Controls are three separate levels of quality control material prepared from human serum with non-serum constituents added. The analytes currently in the control material are: Alphafetoprotein, Carbamazepine, CEA, Digoxin, Cortisol, Gentamicin, Estradiol, Phenobarbital, Ferritin, Phenytoin, Folic Acid, Theophylline, FSH, Tobramycin, HCG, Valproic Acid, IgE, Vancomycin, LH, Progesterone, Prolactin, PSA, T3, T3-free, T4, T4-free, Testosterone, Thyroid Uptake, TSH, TSH-3, Vitamin B12. The intention of this submission is to add the following three constituents to the existing control: Intact PTH (iPTH, or intact parathyroid hormone), Insulin, c-Peptide.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided text, focusing on the absence of detailed performance data as this is a Class I device and the submission primarily concerns adding new analytes to an existing control.

1. Table of Acceptance Criteria and Reported Device Performance

The provided 510(k) summary for the Ligand Plus 1, 2, 3 Controls does not include a table of specific numerical acceptance criteria or reported device performance metrics (e.g., accuracy, precision values, sensitivity, specificity).

This is primarily because:

The device is a Class I quality control material, which typically requires demonstrating that it functions as intended (i.e., provides stable and accurate control values) rather than providing diagnostic results itself.
The submission is for the addition of three new analytes (iPTH, Insulin, and c-Peptide) to an already cleared predicate device. The primary concern is that these new analytes integrate without compromising the control's known function.
The "Substantial Equivalence" section emphasizes the identity of intended use, storage, handling, stability, source material, and instructions for use with the predicate device.

Instead of specific performance numbers, the "acceptance criteria" here would be demonstrating that the new analytes behave as expected for a quality control material and do not negatively impact the overall functionality or existing cleared analytes of the control. This would involve validation studies (which are generally not detailed in a Class I 510(k) summary in this manner) showing the control provides stable, reproducible results when run on the specified instruments.

For a quality control product, "performance" is typically demonstrated by:

Target Value Assignment: Showing that the control can be assigned appropriate target values for the added analytes.
Stability: Demonstrating the stability of the added analytes over the product's shelf-life.
Lot-to-Lot Consistency: Ensuring consistency between different manufacturing lots.
Matrix Effects: Confirming that the control matrix is suitable for the specified assays.

The document implicitly states that these aspects were successfully addressed to achieve substantial equivalence.

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

The 510(k) summary does not specify the sample size used for any test set or the data provenance (e.g., country of origin, retrospective/prospective). This level of detail is typically not required or provided in Class I 510(k) summaries for quality control materials for added analytes to an existing control. Demonstrating "substantial equivalence" for a control material often relies on internal validation studies and comparison to existing methods/materials rather than extensive clinical trial data.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This information is not applicable and not provided.

The device is a quality control material, not a diagnostic device that interprets patient samples. Therefore, "ground truth" as established by experts in clinical interpretation (e.g., radiologists, pathologists) is not relevant to its performance.
Ground truth for a control material involves the accurate assignment of analyte concentrations (target values), which is determined by the manufacturer through rigorous analytical methods and reference measurements, not by expert consensus on clinical findings.

4. Adjudication Method for the Test Set

This information is not applicable and not provided for the same reasons as #3. Adjudication by experts is relevant for diagnostic devices interpreting complex clinical data, not for the analytical performance of a quality control material.

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

A MRMC comparative effectiveness study was not done. This type of study focuses on the impact of a diagnostic tool on human reader performance (e.g., radiologists, pathologists) in interpreting medical images or complex data. Since the device is a quality control material (for in vitro diagnostic use to monitor precision and accuracy of immunochemistry tests), human interpretation of results is not directly assessed in the way an MRMC study would measure. Its role is to ensure the analyzers are performing correctly.

6. Standalone Performance Study

While not explicitly called a "standalone performance study" in the context of diagnostic algorithms, the underlying studies to support the addition of the new analytes would involve standalone analytical performance evaluations of the control material itself. These studies would assess:

Assigned values and expected ranges for iPTH, Insulin, and c-Peptide.
Reproducibility (precision) of these analytes when measured on the ADVIA Centaur® and ACS:180® Systems.
Stability of these analytes in the control matrix over time and under various storage conditions.
Homogeneity within and between vials.

The positive outcome of these internal analytical studies would have formed the basis for the submission, allowing the FDA to deem the device "substantially equivalent."

7. Type of Ground Truth Used

The "ground truth" for a quality control material like this involves analytically derived target values and acceptable ranges for the analytes. These would be established by:

Reference measurement procedures: Highly accurate and precise laboratory methods (often traceable to international reference materials).
Interlaboratory studies: Testing the control material across multiple qualified laboratories to establish consensus values.
Manufacturer's internal validation: Extensive testing using the intended platform (ADVIA Centaur® and ACS:180® Systems) to determine the expected values and performance characteristics.

This is not "expert consensus" in the clinical sense, nor is it based on pathology or outcomes data. It is purely analytical.

8. Sample Size for the Training Set

This information is not applicable and not provided. "Training set" refers to data used to train machine learning algorithms. This device is a biochemical control material, not an AI or machine learning-based diagnostic device.

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

This information is not applicable and not provided for the same reasons as #8.

Summary

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Summary of Safety and Effectiveness

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:________________________________________________________________________________________________________________________________________________

MAR 0 3 2003

Submitter's Name and Address

Bayer Healthcare LLC 511 Benedict Avenue Tarrytown, NY 10591 Establishment Registration Number: 2432235

Contact Person: Kenneth T. Edds, Ph.D. Telephone: 914-524-2446 Fax: 914-524-2500 e-mail: ken.edds.b@bayer.com

Contract Manufacturer

Bio-Rad Laboratories 9500 Jeronimo Road Irvine, CA 92618 Establishment Registration: 2016706 Owner Operator Number: 9929003

Device Name:
Proprietary/Trade Name
Common Name:
Classification Name:
Classification:
Regulation Number:
Panel:
Product Code:

Ligand Plus 1,2,3 Controls Bayer Ligand Plus 1,2,3 Quality Control Material Enzyme Controls (assayed and unassayed) Class I 21 CFR 862.1660 Chemistry (75) JJY

Predicate Device:

Ligand Plus 1,2,3 Controls Premarket Notification Number: K901212

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Device Description:

The Ligand Plus 1, 2, 3 Controls are three separate levels of quality control material prepared from human serum with non-serum constituents added. The analytes currently in the control material are:

Alphafetoprotein	Carbamazepine
CEA	Digoxin
Cortisol	Gentamicin
Estradiol	Phenobarbital
Ferritin	Phenytoin
Folic Acid	Theophylline
FSH	Tobramycin
HCG	Valproic Acid
IgE	Vancomycin
LH
Progesterone
Prolactin
PSA
T3
T3-free
T4
T4-free
Testosterone
Thyroid Uptake
TSH
TSH-3
Vitamin B12

The intention of this submission is to add the following three constituents to the existing control: Intact PTH (iPTH, or intact parathyroid hormone) Insulin c-Peptide

Intended Use:

The Ligand Plus 1, 2, and 3 controls are assayed control materials for in vitro diagnostic use to monitor the precision and accuracy of immunochemistry test procedures for the ADVIA Centaur® andACS:180® Systems.

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Substantial Equivalence:

The Ligand Plus 1, 2, and 3 controls are identical in intended use, storage and handling, stability, source material (human serum), and instructions for use as the previously cleared Ligand Plus 1, 2, 3 Controls. The only difference in these controls is the addition of three new analytes: iPTH, Insulin, and c-Peptide.

As with the predicate device, the control material is lyophilized and requires reconstitution with 5.0 mL reagent grade water. These controls are only for use on the Bayer ADVIA Centaur and ACS:180 Systems.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines above three wavy lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 0 3 2003

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Baver HealthCare LLC Diagnostics Division 511 Benedict Avenue Tarrytown, NY 10591-5097

Re: K030452

Trade/Device Name: Ligand Plus 1, 2, 3 Controls Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: Class I Product Code: JJY Dated: February 6, 2003 Received: February 11, 2003

Dear Dr. Edds:

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 Sutman

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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Page 1 of 1 510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: Ligand Plus1, 2, 3

Indications for Use:

Assayed control material for in vitro diagnostic use to monitor the precision and accuracy of immunochemistry test procedures for the ADVIA Centaur® andACS:180® Systems.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use

Over-The-Counter Use

(Per 21 CFR 801.109)

(Optional Format 1-2-96)

Sean Cooper

(Division Sign-Off) Division of Clinical Laboratory D 510(k) Number ________________________________________________________________________________________________________________________________________________________________

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.