The Dimension® TACR Flex® reagent cartridge is an in vitro diagnostic test intended to quantitatively measure tacrolimus in human whole blood on the Dimension® clinical chemistry system. Measurements of tacrolimus are used as an aid in the management of tacrolimus therapy in kidney and liver transplant patients.

Device Description

The Dimension® TACR Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight-well cartridge for use on the Dade Behring Dimension® clinical chemistry system.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the Dimension® TACR Flex® reagent cartridge, an in vitro diagnostic device used to measure tacrolimus in human whole blood. The submission aims to demonstrate substantial equivalence to a predicate device, the Abbott IMx® Tacrolimus II Assay.

Here's an analysis of the acceptance criteria and study information based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in terms of pre-defined thresholds for slope, intercept, or correlation coefficient. Instead, it presents the results of method comparison studies and implies that these results are considered acceptable for demonstrating substantial equivalence. The predicate device's assay range (1.5-30 ng/mL) is a point of comparison for the new device's range (1.2-30 ng/mL).

However, based on the provided comparative method tables, we can deduce what was measured:

Metric	Acceptance Criteria (Implied)	Reported Device Performance (Dimension® TACR Flex® vs LC/MS/MS)	Reported Device Performance (Dimension® TACR Flex® vs Abbott IMx®)
Slope	Not explicitly stated as a numerical range; likely expected to be close to 1.0, indicating proportional agreement.	All samples: 1.13Kidney: 1.16Liver: 1.06	All samples: 0.92Kidney: 0.90Liver: 0.93
Intercept	Not explicitly stated as a numerical range; likely expected to be close to 0.0, indicating absence of constant bias.	All samples: -0.27Kidney: -0.60Liver: 0.49	All samples: 0.10Kidney: -0.06Liver: 0.45
r-value	Not explicitly stated as a numerical threshold; likely expected to be high (e.g., >0.85 or >0.90), indicating strong linear correlation.	All samples: 0.88Kidney: 0.88Liver: 0.88	All samples: 0.85Kidney: 0.87Liver: 0.82
Assay Range	Comparable to predicate device (Abbott IMx®: 1.5-30 ng/mL)	1.2-30 ng/mL	N/A (this is a characteristic of the device itself)

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

Sample Size for Test Set:
- Vs. LC/MS/MS: 184 samples (103 kidney, 81 liver)
- Vs. Abbott IMx® Tacrolimus II Assay: 175 samples (97 kidney, 78 liver)
Data Provenance:
- Country of Origin: Not explicitly stated, but the studies were conducted at "two external sites." This usually implies clinical sites within the country where regulatory approval is sought (e.g., USA for FDA submission) unless specified otherwise.
- Retrospective or Prospective: Not explicitly stated. However, "samples from 2 transplant patient groups (liver and kidney) were included in the studies" suggests these were patient samples collected for the purpose of the study, making it likely a prospective or retrospectively collected cohort specifically for this validation. Given the date of submission (2006), it's more probable that these were prospectively collected samples from transplant patients.

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

This information is not applicable to this type of device. For in vitro diagnostic assays measuring a quantitative analyte like tacrolimus, the "ground truth" is typically established by a highly sensitive and specific reference method (like LC/MS/MS) or a well-established, legally marketed comparative method (like the Abbott IMx® assay). There are no human experts involved in "scoring" or "interpreting" the results to establish ground truth in the way there would be for image-based diagnostic AI.

4. Adjudication Method for the Test Set

This is not applicable. Adjudication methods (like 2+1, 3+1) are used to resolve discrepancies in human expert interpretations, especially in studies involving subjective assessments (e.g., image-based diagnostics). For quantitative chemical assays, the agreement is determined mathematically by statistical methods (e.g., Passing Bablok regression) between the test device and the reference/predicate method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. Without AI Assistance

This information is not applicable. This device is an in vitro diagnostic reagent cartridge for laboratory testing, not an AI-assisted diagnostic tool that aids human readers (e.g., radiologists interpreting images). Therefore, no MRMC study or AI assistance effect size is relevant.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented are essentially standalone performance studies of the Dimension® TACR Flex® reagent cartridge. The device provides a quantitative measurement of tacrolimus. Its performance is evaluated directly against established methods (LC/MS/MS and the Abbott IMx® Tacrolimus II Assay) without human intervention in the result generation itself. The results (slope, intercept, r-value) characterize the algorithm/device's performance.

7. The Type of Ground Truth Used

The ground truth used was:

Reference Method: Liquid Chromatography / Tandem Mass Spectrometry (LC/MS/MS)
Comparative Method: Abbott IMx® Tacrolimus II Assay (a predicate device)

8. The Sample Size for the Training Set

The document does not explicitly mention a separate training set for this device. For in vitro diagnostic assays like this, it is common that:

The assay's formulation and optimization would occur during development using a variety of samples and calibrators, which could be considered an internal "training" phase for the assay itself.
The statistical analysis (Passing Bablok regression) is performed on the entire test set against the reference or predicate method.

If the device involved a machine learning algorithm, a dedicated training set would be described. Since it's an immunoassay, the "training" analogous to ML would be the assay development and calibration process. The document only describes the validation (test set) data.

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

As no specific "training set" for an explicit algorithm is mentioned, this question is not directly applicable. For the development and calibration of the immunoassay, the "ground truth" would be established using:

Highly purified tacrolimus standards.
Reference methods like LC/MS/MS to assign values to calibrator materials.
Internal validation and quality control procedures.

Summary

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MAY 1 8 2006

510(k) Summary Dimension® TACR Flex® reagent cartridge

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:

The assigned 510(k) number is: صحب 60 حي

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

Manufacturer:

Dade Behring Inc. P.O. Box 6101 Newark, DE 19714

Contact Information:

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

Date of Preparation:

May 2, 2006

2. Device Name / Classification

Dimension® TACR Flex® reagent cartridge / Class II

3. Identification of the Predicate Device

Abbott IMx® Tacrolimus II Assay, P970007 (Note: Tacrolimus test systems have been reclassified into Class II since the predicate was approved.)

4. Device Description

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ડ. Device Intended Use

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

The Dimension® TACR Flex® reagent cartridge is substantially equivalent in intended use and technological characteristics to the Abbott IMx® Tacrolimus II Assay. Both devices are immunoassays intended for use in the quantitative measurement of tacrolimus in human whole blood. The Dimension® TACR Flex® reagent cartridge has an assay range of 1.2-30 ng/mL. The Abbott IMx® Tacrolimus II Assay has an assay range of 1.5-30 ng/mL

Comparison Information

Method comparison studies were conducted at two external sites comparing the Dimension® TACR Flex® reagent cartridge against two predicates:

. liquid chromatography / tandem mass spectrometry (LC/MS/MS) and
the Abbott IMx® Tacrolimus II Assay.

Samples from 2 transplant patient groups (liver and kidney) were included in the studies. The data from both sites were pooled and analyzed by Passing Bablok linear regression.

Comparative Method

LC/MS/MS	Slope	Intercept	r	n
All samples	1.13	-0.27	0.88	184
Kidney	1.16	-0.60	0.88	103
Liver	1.06	0.49	0.88	81
Abbott IMx® Tacrolimus II Assay
All samples	0.92	0.10	0.85	175
Kidney	0.90	-0.06	0.87	97
Liver	0.93	0.45	0.82	78

・・・・・・・・

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA" is arranged in a circular pattern around the eagle. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 18 2006

Ms. Yuk-Ting Lewis Regulatory Affairs & Compliance Manager Dade Behring, Inc. PO Box 6101, M/S 514 Newark, DE 19714

K060502 Trade/Device Name: Dimension® TACR Flex® reagent cartridge Regulation Number: 21 CFR§862.1678 Regulation Name: Tacrolimus test system Regulatory Class: Class II Product Code: MLM Dated: April 20, 2006 Received: April 21, 2006

Dear Ms. Lewis:

Re:

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 (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 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): くつんてここ

Dimension® TACR Flex® reagent cartridge Device Name:

Indications For Use:

. . . . . . .

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)

C.A. Cox

Division Sigh-Off

210(K)

Office of In Vitro Diaznostic Device Evaluation and Safet

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Regulation Number and Section

§ 862.1678 Tacrolimus test system.

(a)
Identification. A tacrolimus test system is a device intended to quantitatively determine tacrolimus 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 tacrolimus.(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.