The Emit® 2000 Cyclosporine Specific Assay is for in vitro quantitative analysis of cyclosporine (CsA) in human whole blood as an aid in the management of cyclosporine therapy in kidney, heart and liver transplant patients.

Device Description

The Emit® 2000 Cyclosporine Specific Assay employs a homogeneous enzyme immunoassay technique used for the analysis of cyclosporine in whole blood. The assay contains mouse monoclonal antibodies with a high specificity for cyclosporine. The Emit® 2000 Cyclosporine Specific Assay is based on competition for cyclosporine antibody binding sites. Cyclosporine in the sample competes with cyclosporine in Enzyme Reagent B that is labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH). Active (unbound) enzyme converts the oxidized nicotinamide adenine dinucleotide (NAD) in Antibody Reagent A to NADH, resulting in a kinetic absorbance change that can be measured spectrophotometrically. Enzyme activity decreases upon binding to the antibody, allowing the cyclosporine concentration in the sample to be measured in terms of enzyme activity. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.

AI/ML Overview

The provided text describes the 510(k) submission for the Emit® 2000 Cyclosporine Specific Assay. It outlines the device's intended use and presents comparative method studies to demonstrate its performance against predicate devices and a reference method.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the results of the comparative method studies demonstrating substantial equivalence to the predicate devices and an established reference method (LC/MS). The performance is presented in terms of linear regression analysis (slope, intercept, and correlation coefficient 'r').

Comparison Method	Acceptance Criteria (Implicit from Predicate & LC/MS)	Reported Device Performance (Emit® 2000 vs. Comparative Method)
LC/MS (Reference Method)
All samples	High correlation (r close to 1), slope close to 1, small intercept	Slope: 1.01, Intercept: 36.07, r: 0.971 (n=138)
Heart	High correlation, slope close to 1, small intercept	Slope: 1.04, Intercept: 19.00, r: 0.989 (n=33)
Liver	High correlation, slope close to 1, small intercept	Slope: 1.00, Intercept: 42.11, r: 0.971 (n=40)
Kidney	High correlation, slope close to 1, small intercept	Slope: 1.14, Intercept: -49.0, r: 0.951 (n=59)
Abbott TDx®/TDxFLx® CSA Monoclonal Whole Blood Assay (Predicate Device)
All samples	High correlation (r close to 1), slope close to 1, small intercept	Slope: 1.13, Intercept: -92.4, r: 0.969 (n=134)
Heart	High correlation, slope close to 1, small intercept	Slope: 1.12, Intercept: -86.6, r: 0.976 (n=33)
Liver	High correlation, slope close to 1, small intercept	Slope: 1.14, Intercept: -102, r: 0.982 (n=40)
Kidney	High correlation, slope close to 1, small intercept	Slope: 1.15, Intercept: -114, r: 0.950 (n=59)

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

Sample Sizes for Test Set:
- LC/MS Comparison: 138 samples (33 Heart, 40 Liver, 59 Kidney)
- Abbott TDx®/TDxFLx® Comparison: 134 samples (33 Heart, 40 Liver, 59 Kidney)
Data Provenance: Banked retrospective samples from 3 transplant patient groups (heart, liver, and kidney). The studies were conducted at two external sites, but the country of origin is not specified.

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

This information is not applicable to this type of device and study. The "ground truth" for this assay is established by quantitative measurement methods (LC/MS and predicate immunoassays), not by expert interpretation of images or clinical cases.

4. Adjudication Method for the Test Set

This information is not applicable to this type of device and study. Adjudication methods (like 2+1, 3+1) are typically used for establishing ground truth in studies involving expert review of qualitative data (e.g., medical images). Here, the comparison is against established quantitative measurement methods.

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

No. This is not a diagnostic imaging device or an AI-assisted interpretation tool. It is a quantitative assay, and therefore, an MRMC comparative effectiveness study involving human readers with and without AI assistance is not relevant or performed for this device.

6. Standalone Performance Study

Yes, a standalone performance was essentially done. The "Comparative Method" studies analyze the Emit® 2000 Cyclosporine Specific Assay's measurements directly against the reference (LC/MS) and predicate immunoassay results. This demonstrates the algorithm's (assay's) performance in generating quantitative values for cyclosporine in whole blood.

7. Type of Ground Truth Used

The ground truth used consisted of:

A "gold standard" quantitative measurement: Liquid Chromatography / Mass Spectrometry (LC/MS) for cyclosporine concentration.
A legally marketed predicate device: Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay. This serves as a comparative benchmark to demonstrate substantial equivalence.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" or its sample size. This assay is a chemical immunoassay, not a machine learning model that typically requires a distinct training phase with labeled data. The development of the assay reagents and protocols would involve internal validation and optimization, but not in the same sense as a machine learning training set.

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

As there is no explicit "training set" in the context of a machine learning model, this question is not strictly applicable. The "ground truth" (reference measurements) for the assay's development and validation would have been established through a combination of methods, including the use of known concentration standards, spiked samples, and potentially comparisons to existing reference methods during assay development. However, the document does not detail these developmental stages, focusing instead on the performance evaluation for regulatory submission.

Summary

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-EB G 2006

510(k) Summary Emit® 2000 Cyclosporine Specific Assay

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.

The assigned 510(k) number is:

K053061

1. Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation

Manufacturer:

Contact Information:

Dade Behring Inc. 20400 Mariani Ave. Cupertino, CA 95014

Dade Behring Inc. P.O. Box 6101 Newark, DE 19714 Attn: Yuk-Ting Lewis Tel: 302-631-7626

Date of Preparation: Oct. 14, 2005

2. Device Name / Classification

Emit® 2000 Cyclosporine Specific Assay / Class II

3. Identification of the Predicate Device

Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay, P890025

4. Device Description

The Emit® 2000 Cyclosporine Specific Assay is based on competition for cyclosporine antibody binding sites. Cyclosporine in the sample competes with cyclosporine in Enzyme Reagent B that is labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH). Active (unbound) enzyme converts the oxidized nicotinamide adenine dinucleotide (NAD) in Antibody Reagent A to NADH, resulting in a kinetic absorbance

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change that can be measured spectrophotometrically. Enzyme activity decreases upon binding to the antibody, allowing the cyclosporine concentration in the sample to be measured in terms of enzyme activity. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.

5. Device Intended Use

6. Medical device to which equivalence is claimed and comparison information

The Emit® 2000 Cyclosporine Specific Assay is substantially equivalent in intended use and technological characteristics to the Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay. Both devices are immunoassays intended for use in the quantitative measurement of cyclosporine in human whole blood. The Emit® 2000 Cyclosporine Specific Assay has an assay range of 40-500 ng/mL or 350-2000 ng/m1. The Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay has an assay range of 25-1500 ng/mL

Comparison Information

Method comparison studies were conducted at two external sites comparing the extended range Emit® 2000 Cyclosporine Specific Assay against two predicates:

the Abbott TDx®/TDxFLx® Cyclosporine Monoclonal Whole Blood Assay, and .
liquid chromatography / mass spectrometry (LC/MS) .

Banked retrospective samples from 3 transplant patient groups (heart, liver and kidney) were used in the studies. The data from both sites were pooled and analyzed by linear regression.

Comparative Method

LC/MS	Slope	Intercept	r	n
All samples	1.01	36.07	0.971	138
Heart	1.04	19.00	0.989	33
Liver	1.00	42.11	0.971	40
Kidney	1.14	-49.0	0.951	59
Abbott TDx®/TDx/FLx® CSA Monoclonal Whole Blood Assay
All samples	1.13	-92.4	0.969	134
Heart	1.12	-86.6	0.976	33
Liver	1.14	-102	0.982	40
Kidney	1.15	-114	0.950	59

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus, which is a symbol often associated with medicine and healthcare. The caduceus is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)", which is arranged in a circular fashion around the symbol.

Public Health Service

FEB 6 2006 Food and Drug Administratio 2098 Gaither Road Rockville MD 20850

Yuk-Ting Lewis Regulatory Affairs and Compliance Manager Dade Behring, Inc. P.O. Box 6101 M/S 514 Newark, DE 19714

Re: K053061

Trade/Device Name: Emit®2000 Cyclosporine Specific Assay Regulation Number: 21 CFR§ 862.1235 Regulation Name: Cyclosporine test system Regulatory Class: Class II Product Code: MKW Dated: January 6, 2006 Received: January 13, 2006

Dear Yuk-Ting:

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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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 (240) 276-0484. 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/industry/support/index.html.

Sincerely yours,

Alberto
Alberto Gutierrez, Ph.D.

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Emit® 2000 Cyclosporine Specific Assay Device Name:

Indications For Use:

The Emit® 2000 Cyclosporine Specific Assay is for in vitro quantitative analysis of cyclosporine therany in kidney, The Emit® 2000 Cyclosportifie Spective Assay is for in Ville qualified by the first of the management of cyclosporine therapy in kidney, heart and liver transplant patients.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _ (21 CFR 801)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Ana Choppie

Page 1 of 1

Office of In Vitro Diagnostic Device _valuation and Safety

v 53061

Regulation Number and Section

§ 862.1235 Cyclosporine test system.

(a)
Identification. A cyclosporine test system is a device intended to quantitatively determine cyclosporine concentrations as an aid in the management of transplant patients receiving therapy with this drug. This generic type of device includes immunoassays and chromatographic assays for cyclosporine.(b)
Classification. Class II (special controls). The special control is “Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA.” See § 862.1(d) for the availability of this guidance document.