CYCLOSPORINE EXTENDED RANGE ASSAY (CSAE) FLEX REAGENT CARTRIDGE, CATALOG # DF108

• K Number: K052017
• Device Name: CYCLOSPORINE EXTENDED RANGE ASSAY (CSAE) FLEX REAGENT CARTRIDGE, CATALOG # DF108
• Manufacturer: DADE BEHRING, INC.
• Date Cleared: 2005-09-01 ( 37 days)
• Product Code: MKW
• Regulation Number: 862.1235

Intended Use

The Cyclosporine CSAE Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood for the Dimension® clinical chemistry system. Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients.

Device Description

The Dimension® CSAE Cyclosporine Flex® reagent cartridge (DF108) is an in vitro rine Differences that consists of prepackaged reagents in a plastic eight well cartridge for use on the Dade Behring Dimension® clinical chemistry system for the quantitative determination cyclosporine A (CSA) in human whole blood.

Predicate Devices

P890025

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard in vitro diagnostic test using prepackaged reagents and a clinical chemistry system. There is no mention of AI, ML, or any related technologies. The performance studies focus on traditional analytical methods like reproducibility, linearity, interference, and recovery.

Therapeutic

No

Explanation: The device is an in vitro diagnostic test for measuring cyclosporine A, used as an aid in patient management, not as a direct therapeutic intervention.

Diagnostic

Yes
The "Intended Use / Indications for Use" states that the device is "an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood" and that "Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients". This clearly indicates its use in diagnosis and patient management.

SaMD (Software as a Medical Device)

No

The device description clearly states it is a "reagent cartridge" and a "plastic eight well cartridge," indicating it is a physical component containing reagents, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

• Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood".
• Device Description: The "Device Description" also refers to the device as an "in vitro rine Differences" (likely a typo for "in vitro diagnostic") and describes it as a reagent cartridge for use on a clinical chemistry system for the quantitative determination of cyclosporine A in human whole blood.
• Performance Studies: The "Summary of Performance Studies" describes testing performed on human specimens (whole blood) to evaluate the device's performance, which is typical for IVD devices.
• Predicate Device: The mention of a "Predicate Device(s)" with a K number (P890025) indicates that this device is being compared to a previously cleared IVD device, which is a common regulatory pathway for IVDs.

All of these points strongly indicate that the device is intended for in vitro diagnostic use.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Cyclosporine CSAE Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood for the Dimension® clinical chemistry system. Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients.

Product codes

MK W

Device Description

The Dimension® CSAE Cyclosporine Flex® reagent cartridge (DF108) is an in vitro rine Differences that consists of prepackaged reagents in a plastic eight well cartridge for use on the Dade Behring Dimension® clinical chemistry system for the quantitative determination cyclosporine A (CSA) in human whole blood .

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

1. Reproducibility
Reproducibility testing was done in accordance with the CLSI/NCCLS Approved Guideline for Evaluation of Precision Performance of Clinical Chemistry Devices (EPS-A. Feb.1999). Specimens at each level were analyzed in duplicate, once a day, for 20 days. The within-run (repeatability) and total (within-lab) standard deviations were calculated by analysis of variance (ANOVA) method.

Material	Mean Units [SI Units]	Standard Deviation (%CV) Repeatability	Within-lab
Whole Blood pool 1	368.0 [306.2]	12.21 [10.16] (3.32)	19.00 [15.81] (5.16)
Whole Blood pool 2	1123.3 [934.6]	30.65 [25.50] (2.73)	57.24 [47.62] (5.10)
Whole Blood pool3	1750.1 [1456.1]	46.72 [38.87] (2.64)	104.07 [86.59] (5.29)
More Control 1	488.7 [406.6]	13.99 [11.64] (2.86)	28.77 [23.94] (5.89)
More Control 2	866.1 [720.6]	18.61 [15.48] (2.15)	47.71 [39.69] (5.51)
More Control 3	1301.9 [1083.2]	34.41 [28.63] (2.64)	68.89 [57.32] (5.29)

2. Method Comparison
A total of 140 specimens were tested with the Dimension® CSAE assay, with the Abbott TDx /TDx FLx Cyclosporine Monoclonal Whole Blood Assay and by LC/MS technology. Linear regression was used to calculate a slope, intercept and correlation coefficient. The model equation for regression statistics is: Result of Dimension® system = (Slope x comparative method result) + Intercept.

Comparative Method	Slope	Intercept ng/mL[umol/L]	Correlation Coefficient	n
Abbott TDx®
All	1.13	-67.2	0.980	140
Heart	0.996	2.52	0.982	35
Liver	1.11	-61.7	0.970	40
Kidney	1.09	-32.3	0.973	60
LCMS
All	1.09	17.1	0.986	140
Heart	0.93	93.7	0.983	35
Liver	1.00	59.9	0.980	40
Kidney	1.10	15.2	0.990	60

3. Linearity
Standard solutions were prepared by sequential mixing to create a set of eight equally spaced sample pools starting with a high and low pool of known analyte concentration. Theoretical concentrations were computed for all intermediate pools based on the initial concentrations of the high and low pools. The analysis of cyclosporine on the Dimension® RxL by the Dimension® CSAE method shows a deviation from the estimated line of less than 15 ng/mL [12.5 nmol/L] with 95% confidence at the analytical concentration of 794.5 ng/mL [662.1 nmol/L]. The lower limit of the linearity claim is 350.0 ng/mL [291.7 nmol/L].

4. Interference Testing
Interference testing was performed according to the CLSI/NCCLS Protocol EP-7A. A summary of the substances that do not interfere with the Dimension® Cyclosporine methods when present in whole blood at the concentrations indicated. Inaccuracies (biases) due to these substances are less than 10% at a CSA level equivalent to 800 ng/mL [665.6 nmol/L] can be found in the package insert.

5. Analytical Specificity
Six major metabolites were evaluated for cross-reactivity in the presence of 500 ng/mL [416 nmol/L] cyclosporine. The percent cross-reactivity was calculated as follows:
% cross reactivity = (measured CSA-control CSA (500 ng/mL) [41.6 nmol/L] x 100) / metabolite added

Cyclosporine Metabolite	Metabolite Level Tested ng/mL [nmol/L]	Cross-Reactivity %
AM1 (M17)	1000 [821]	4.7
AM1c (M18)	1000 [821]	2.1
AM1c9 (M26)	1000 [810]	3.9
AM4N (M21)	1000 [842]	3.1
AM9 (M1)	1000 [821]	2.4
AM19 (M8)	1000 [810]	3.0

6. Recovery
Known amounts of CSA were added to human whole blood samples with concentrations of 610.0, 1232.2, and 1861.8 ng/mL [507.5, 1025.2, 1861.8 nmol/L]. CSA concentrations on these samples were then measured and the calculated percent recovery ranged from 94.3% to 103.1% with a mean recovery of 101.0%.

7. Functional Sensitivity
The functional sensitivity of the CSAE method was demonstrated to be less than 110 ranetional benefits 110 visual sensitivity is defined as the lowest concentration at which the intra-assay coefficient of variation is not greater than 20%.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

P890025

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

0

SEP - 1 2005

510(k) Summary for the Dimension® Cyclosporine CSAE Flex® reagent cartridge (DF108)

A. 510(k) Number: K052017

B. Analyte: Cyclosporine

C. Type of Test: qualitative or quantitative homogeneous enzyme immunoassay

D. Applicant: Dade Behring Inc., P.O. Box 6101, Newark, DE 19714-6101 [phone] Contact: Andrea M. Tasker, Regulatory Affairs and Compliance Manager

E. Proprietary and Established Names: Dimension® Cyclosporine CSAE Flex® reagent cartridge

F. Regulatory Information:

1.Regulation section: 21CFR §862.1235

2. Classification: Class II (Special Controls)

3. Product Code: MK W

4. Panel: Clinical Toxicology Test Systems

G. Intended Use:

l. Intended for Use:

The Cyclosporine CSAE Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood for the Dimension® clinical chemistry system.

2. Indications for Use:

The Cyclosporine CSAE Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood for the Dimension® clinical chemistry system. Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients.

3. Special condition for use statement(s): none

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4. Special instrument Requirements: Dimension® clinical chemistry system with Heterogeneous Module.

H. Device Description:

The Dimension® CSAE Cyclosporine Flex® reagent cartridge (DF108) is an in vitro rine Differences that consists of prepackaged reagents in a plastic eight well cartridge for use on the Dade Behring Dimension® clinical chemistry system for the quantitative determination cyclosporine A (CSA) in human whole blood .

I. Substantial Equivalence Information:

• 1. Predicate Device: Abbott TDx® /TDx FLx® Cyclosporine Monoclonal Whole Blood Assay
     ので、その他の人気の人気の人気の人気の人気の一つです。 一般の一人の一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つの一つ
• 2. Predicate K Number(s): P890025
• 3. Comparison with Predicate:

| Item | Device
Dimension® CSAE
Cyclosporine | Predicate
Abbott TDx® /TDx FLx®
Cyclosporine Assay |
|--------------|--------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For the measurements of
CSA to be used as an aid in
the management of heart,
liver and kidney transplant
patients. | For the measurements of CSA
to be used as an aid in the
management of heart, liver
and kidney transplant
patients. |
| Sample Type | Whole Blood | Whole Blood |
| Technology | Affinity Particle Mediated
Immunoassay | Fluorescence Polarization
Immunoassay |
| Antibody | Mouse monoclonal | Mouse monoclonal |
| Assay Range | 350 -2000ng/mLa | 25 - 1500 ng/mL |

a. The Dimension® CSAE Extended Range Cyclosporine Assay is intended as a high range assay to compliment the low range assay, the Dimension® CSA Cyclosporine Assay, which has an assay range of 25 - 500ng/mL.

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J. Standard/Guidance Document Referenced

1. Guidance;

Class II Special Controls Guidance Document: Cyclosporine and Tacrolimus Assays; Guidance for Industry and FDA, Document issued on: September 16, 2002.

2. Standards;

GP22-A	Continuous Quality Improvement Essential Management Approaches
ISO 15223	Medical devices - Symbols to be used with medical device labeling
and information to be supplied
EN 1441:1997	Medical Devices - Risk Management
ISO 14971-1	Medical devices: Risk management - Part1: Application of
risk analysis
EP9-A2	Method Comparison and Bias Estimation Using Patient Samples
EP7-A	Interference Testing in Clinical Chemistry
EP5-A	Evaluation of Precision Performance of Clinical Chemistry Devices
CEN 13640	Stability testing of In-Vitro Diagnostic Devices

K. Test Principle:

The automated Dimension® CSAE method uses an immunoassay technique in which free and CSA-bound antibody-enzyme species are separated using magnetic particles. The assay is performed using a method specific Flex® reagent cartridge. The calibrators and controls for this assay are sold separately.

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L . Performance Characteristics:

1. Reproducibility

Reproducibility testing was done in accordance with the CLSI/NCCLS Approved Guideline for Evaluation of Precision Performance of Clinical Chemistry Devices (EPS-A. Feb.1999). Specimens at each level were analyzed in duplicate, once a day, for 20 days. The within-run (repeatability) and total (within-lab) standard deviations were calculated by analysis of variance (ANOVA) method.

| Material | Mean
Units [SI Units] | Standard Deviation (%CV)
Repeatability | Within-lab |
|--------------------|--------------------------|-------------------------------------------|-----------------------|
| Whole Blood pool 1 | 368.0 [306.2] | 12.21 [10.16] (3.32) | 19.00 [15.81] (5.16) |
| Whole Blood pool 2 | 1123.3 [934.6] | 30.65 [25.50] (2.73) | 57.24 [47.62] (5.10) |
| Whole Blood pool3 | 1750.1 [1456.1] | 46.72 [38.87] (2.64) | 104.07 [86.59] (5.29) |
| More Control 1 | 488.7 [406.6] | 13.99 [11.64] (2.86) | 28.77 [23.94] (5.89) |
| More Control 2 | 866.1 [720.6] | 18.61 [15.48] (2.15) | 47.71 [39.69] (5.51) |
| More Control 3 | 1301.9 [1083.2] | 34.41 [28.63] (2.64) | 68.89 [57.32] (5.29) |

More Diagnostics Cyclosporine Control is a product of More Diagnostics Inc., Los Osos, CA. 93402

2. Method Comparison

A total of 140 specimens were tested with the Dimension® CSAE assay, with the Abbott TDx /TDx FLx Cyclosporine Monoclonal Whole Blood Assay and by LC/MS technology. Linear regression was used to calculate a slope, intercept and correlation coefficient. The model equation for regression statistics is: Result of Dimension® system = (Slope x comparative method result) + Intercept.

| Comparative
Method | Slope | Intercept
ng/mL[umol/L] | Correlation
Coefficient | n |
|-----------------------|-------|----------------------------|----------------------------|-----|
| Abbott TDx® | | | | |
| All | 1.13 | -67.2 | 0.980 | 140 |
| Heart | 0.996 | 2.52 | 0.982 | 35 |
| Liver | 1.11 | -61.7 | 0.970 | 40 |
| Kidney | 1.09 | -32.3 | 0.973 | 60 |
| LCMS | | | | |
| All | 1.09 | 17.1 | 0.986 | 140 |
| Heart | 0.93 | 93.7 | 0.983 | 35 |
| Liver | 1.00 | 59.9 | 0.980 | 40 |
| Kidney | 1.10 | 15.2 | 0.990 | 60 |

TDx® is the registered trademark of Abbott Diagnostics, Abbott Park, IL 60064

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3. Linearity

Standard solutions were prepared by sequential mixing to create a set of eight equally spaced sample pools starting with a high and low pool of known analyte concentration. Theoretical concentrations were computed for all intermediate pools based on the initial concentrations of the high and low pools. The analysis of cyclosporine on the Dimension® RxL by the Dimension® CSAE method shows a deviation from the estimated line of less than 15 ng/mL [12.5 nmol/L] with 95% confidence at the analytical concentration of 794.5 ng/mL [662.1 nmol/L]. The lower limit of the linearity claim is 350.0 ng/mL [291.7 nmol/L].

4. Interference Testing

Interference testing was performed according to the CLSI/NCCLS Protocol EP-7A. A summary of the substances that do not interfere with the Dimension® Cyclosporine methods when present in whole blood at the concentrations indicated. Inaccuracies (biases) due to these substances are less than 10% at a CSA level equivalent to 800 ng/mL [665.6 nmol/L] can be found in the package insert.

5. Analytical Specificity

Six major metabolites were evaluated for cross-reactivity in the presence of 500 ng/mL [416 nmol/L] cyclosporine. The percent cross-reactivity was calculated as follows:

	% cross reactivity = = measured CSA-control CSA (500 ng/mL) [41.6 nmol/L] x
	100
	metabolite added

Cyclosporine	Metabolite Level Tested	Cross-Reactivity
Metabolite	ng/mL [nmol/L]	%
AM1 (M17)	1000 [821]	4.7
AM1c (M18)	1000 [821]	2.1
AM1c9 (M26)	1000 [810]	3.9
AM4N (M21)	1000 [842]	3.1
AM9 (M1)	1000 [821]	2.4
AM19 (M8)	1000 [810]	3.0

6. Recovery

Known amounts of CSA were added to human whole blood samples with concentrations of 610.0, 1232.2, and 1861.8 ng/mL [507.5, 1025.2, 1861.8 nmol/L]. CSA concentrations on these samples were then measured and the calculated percent recovery ranged from 94.3% to 103.1% with a mean recovery of 101.0%.

Value obtained - Baseline Percent Recovery == ------------------------------------------------------------------------------------------------ x 100 Amount Added

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7. Functional Sensitivity

The functional sensitivity of the CSAE method was demonstrated to be less than 110 ranetional benefits 110 visual sensitivity is defined as the lowest concentration at which the intra-assay coefficient of variation is not greater than 20%.

Final: August 30, 2005

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with its wings spread, symbolizing protection and service. The eagle is positioned within a circular border. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the upper portion of the circle.

Public Health Service

Image /page/6/Picture/3 description: The image shows the text "SEP - 1 2005". The text is written in a simple, sans-serif font. The letters and numbers are all capitalized. The text is likely a date, indicating September 1, 2005.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea Tasker Regulatory Affairs and Compliance Manager Dade Behring, Inc. Glascow Business Community Bldg. 500 Mail Box 514 P.O. Box 6101 Newark, DE 19714-6101

Re: K052017

Trade/Device Name: Dimension® Cyclosporine Extended Range Assay (CSAE) Flex® reagent cartridge Regulation Number: 21 CFR 862.1235 Regulation Name: Cyclosporine test system Regulatory Class: Class II Product Code: MKW Dated: August 23, 2005 Received: August 23, 2005

Dear Ms. Tasker:

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);

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) rms lotter will and my you to FDA finding of substantial equivalence of your device to a legally prerketed 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, rr you destro specific internation and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benam

Carol C. Benson, M.A. Acting 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 Statement

510(k) Number (if known):

K052017

Device Name:

Dimension® CSAE Cyclosporine Extended Range Flex® reagent cartridge

Indications for Use:

The CSAE Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure cyclosporine A (CSA) in human whole blood for the Dimension® clinical chemistry system. Measurements of CSA are used as an aid in the management of heart, liver and kidney transplant patients.

Jam M. Tume
Andrew M. Turner

Andrea M. Tasker Regulatory Affairs and Compliance Manager June 29, 2005

Prescription Use
(Per 21 CFR 801 Subpart D)

AND/OR

Over-the-counter Use (21 CFR 801 Subpart C)

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

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

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safe