The DGTX Flex™ reagent cartridge for the Dimension® clinical chemistry system is an in vitro diagnostic device intended to quantitatively measure digitoxin in human serum and plasma. Measurements of digitoxin are used in the diagnosis and treatment of digitoxin overdose and in monitoring levels of digitoxin to ensure appropriate therapy.

Device Description

The digitoxin assay uses an immunoassay technique in which free and digitoxin-bound antibody-enzyme species are separated using magnetic particles. Digitoxin in the sample is bound by the F(ab')2-ß-galactosidase in the Antibody Conjugate reagent. Magnetic particles coated with the digitoxin analog ouabain are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the digitoxin-antibody-enzyme complex is transferred and mixed with a substrate. The ß-galactosidase (ß-gal) portion of the Digoxin-F(ab')2-βgalactosidase complex catalyzes the hydrolysis of chlorophenol red-β-D galactopyranoside (CPRG) to chlorophenol red (CPR). The change in absorbance at 577 nm due to the formation of CPR is directly proportional to -B-galactosida: e activity. Since ß-galactosidase is not present in serum, its activity is directly proportional to di ¿itoxin in the patient's sample and is measured using a bichromatic (577, 700 nm) rate technique.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:

Acceptance Criteria and Study Details for DGTX Flex™ Reagent Cartridge

1. Acceptance Criteria and Reported Device Performance

The provided document defines substantial equivalence based on the correlation with a predicate device. The primary acceptance criteria are derived from this comparative study.

Acceptance Criteria	Reported Device Performance
Correlation with Predicate Device (aca® DGTX assay):	Correlation coefficient (r): 0.952
- High correlation coefficient (ideally close to 1)	Slope: 1.06
- Slope ideally close to 1	Intercept: -0.6
- Intercept ideally close to 0
Intended Use Equivalence:	The DGTX Flex™ reagent cartridge is intended to quantitatively measure digitoxin (DGTX) in human serum and plasma, which is consistent with the general function of digitoxin test systems.
Methodology Equivalence:	While methodology differs (Affinity particle mediated immunoassay vs. Affinity column mediated immunoassay), the study demonstrates equivalent performance, justifying the different approaches.
Sample Type Equivalence:
- Serum and/or plasma	The DGTX Flex™ uses serum and plasma, while the predicate used serum. The split sample comparison would have validated performance across the shared sample type (serum) and implicitly indicated acceptable performance for plasma if included in the 93 clinical samples.

2. Sample Size and Data Provenance

Sample Size for Test Set: 93 clinical patient samples.
Data Provenance: The document does not explicitly state the country of origin. However, the submission is to the U.S. FDA, and the product is intended for the U.S. market, suggesting the data is likely relevant to the U.S. patient population if not collected therein. The data is retrospective, as it's a "split sample comparison" using existing clinical patient samples.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number of experts used or their qualifications to establish ground truth for the test set.

4. Adjudication Method

The document does not specify an adjudication method. In a split-sample comparison for an analytical device, the "ground truth" is typically the result from the predicate device itself, or a reference method that the predicate device was previously validated against.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging or interpretation devices where human readers provide an assessment. The DGTX Flex™ is an in vitro diagnostic reagent cartridge for quantitative measurement, not a device requiring human interpretation of images or complex data.

6. Standalone Performance Study

Yes, a form of standalone performance was conducted, but it's framed as a comparison to a predicate device, not as an absolute standalone validation against a gold standard that is independent of any existing device. The correlation study directly assesses the performance of the DGTX Flex™ reagent cartridge on the Dimension® clinical chemistry system.

7. Type of Ground Truth Used

The ground truth for the test set was the results obtained from the predicate device, the aca® DGTX assay. This is evident from the "split sample comparison," where both the new device and the predicate device analyzed the same clinical samples, and the predicate's results served as the reference for comparison.

8. Sample Size for Training Set

The document does not specify a training set size. For an IVD reagent, method development typically involves extensive internal validation and optimization, but a distinct "training set" in the context of machine learning (where this term is often used) is not applicable here. The "93 clinical patient samples" refer to the test set used for the substantial equivalence comparison.

9. How Ground Truth for Training Set Was Established

As no specific training set is mentioned in the context of the substantial equivalence claim, the method for establishing its ground truth is not applicable/not provided in this document. During the development of the assay, calibration and internal validation would have been performed using methods established for quantitative assays, likely involving certified reference materials or highly characterized samples.

Summary

{0}------------------------------------------------

3/31/99

K990251

DADE BEHRING

DADE BEHRING INC. P.O. Box 6101 Newark, DE 19714

Summary of Safety and Effectiveness Information

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.

Submitter's Name:	Cathy P. CraftDade Behring Inc.P.O. Box 6101Newark, DE 19714-6101
Date of Preparation:	1/22/99
Name of Product:	DGTX Flex™ reagent cartridge
FDA Classification Name:	Digitoxin Test System
Predicate Device:	aca® Digitoxin Method (K891094)

Device Description: The digitoxin assay uses an immunoassay technique in which free and digitoxin-bound antibody-enzyme species are separated using magnetic particles. Digitoxin in the sample is bound by the F(ab')2-ß-galactosidase in the Antibody Conjugate reagent. Magnetic particles coated with the digitoxin analog ouabain are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the digitoxin-antibody-enzyme complex is transferred and mixed with a substrate. The ß-galactosidase (ß-gal) portion of the Digoxin-F(ab')2-βgalactosidase complex catalyzes the hydrolysis of chlorophenol red-β-D galactopyranoside (CPRG) to chlorophenol red (CPR). The change in absorbance at 577 nm due to the formation of CPR is directly proportional to -B-galactosida: e activity. Since ß-galactosidase is not present in serum, its activity is directly proportional to di ¿itoxin in the patient's sample and is measured using a bichromatic (577, 700 nm) rate technique.

Intended Use: The DGTX Flex™ reagent cartridge is used in the Dimension® clinical chemistry system to quantitatively measure digitoxin (DGTX) in human serum and plasma.

Comparison to Predicate Device:

Item	Dimension® DGTX	aca® DGTX
Sample Type	serum and plasma	serum
Antibody	monoclonal	polyclonal
Methodology	Affinity particlemediated immunoassay	Affinity columnmediated immunoassay
Detection	Bichromatic rate(577 and 700 nm)	Monochromatic rate(405 nm)

{1}------------------------------------------------

Comments on Substantial Equivalence:

Split sample comparison between the DGTX Flex™ reagent cartridge on the Dimension® clinical chemistry system and the aca® DGTX assay gave a correlation coefficient of 0.952, slope of 1.06, and an intercept of -0.6 when tested with 93 clinical patient samples.

The DGTX Flex™ reagent cartridge is substantially equivalent in principle and Conclusion: performance to the aca® DGTX assay based on the split sample comparison discussed above.

Cathy P. Craft

Cathy P. Craft Regulatory Affairs and Compliance Manager Date:

{2}------------------------------------------------

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 features a stylized eagle with three curved lines representing its wings. The eagle is positioned within a circle that contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

Public Health Service

MAR 3 1 1999

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Ms. Cathy P. Craft Regulatory Affairs and Compliance Manager DADE BEHRING, INC. P.O. Box 6101 Newark, Delaware 19714

K990251 Re:

Trade Name: Digitoxin (DGTX) Flex™ Reagent Cartridge Regulatory Class: II Product Code: LFM Dated: January 22, 1999 Received: January 27, 1999

Dear Ms. Craft:

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.

{3}------------------------------------------------

Page 2

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

{4}------------------------------------------------

Indications For Use Statement

Device Name: DGTX Flex™ reagent cartridge

Indications for Use:

Sean Cooper

(Division Sign-Off) Division of Clinical Laboratory Devices K 990251 510(k) Number

Cathy P. Craft Regulatory Affairs and Compliance Manager

January 22, 1999

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-the-counter Use_

(Optional format 1-2-96)

Regulation Number and Section

§ 862.3300 Digitoxin test system.

(a)
Identification. A digitoxin test system is a device intended to measure digitoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digitoxin overdose and in monitoring levels of digitoxin to ensure appropriate therapy.(b)
Classification. Class II.