The Chiron Diagnostics ACS:180 Digitoxin Assay is for the quantitative determination of digitoxin in serum or plasma using the Chiron ACS:180 Automated Chemiluminescence System. Monitoring of serum digitoxin concentrations is necessary to maintain therapeutic efficacy and avoid toxicity. Serum digitoxin levels combined with other therapeutic and clinical information provide the clinician with useful information to aid in adjusting patient dosage, achieving optimal therapeutic effect, and avoiding useless subtherapeutic or harmful toxic doses.

Device Description

The Chiron Diagnostics ACS:180 Digitoxin assay is a competitive immunoassay using direct, chemilumenescent technology. Digitoxin in the patient sample competes with digitoxin, which is covalently coupled to the paramagnetic particles in the Solid Phase for binding to the acridinium ester-labeled monoclonal anti-digitoxin antibody in the Lite Reagent. An inverse relationship exists between the amount of digitoxin in the patient sample and the amount of relative light units (RLUs) detected by the ACS:180® system.

AI/ML Overview

The provided document describes the Chiron Diagnostics ACS Digitoxin assay, comparing its performance to an alternate fluorescence polarization (FPIA) method.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied)	Reported Device Performance (ACS Digitoxin)
Sensitivity	Minimum detectable concentration adequate for clinical use	Measures up to 80 ng/mL, with a minimum detectable concentration of 1.5 ng/mL
Accuracy (Correlation to FPIA)	Strong correlation to established method (Predicate Device: TDX Digitoxin Immunoassay, Abbott Laboratories)	Correlation coefficient (r) = 0.83 (for 608 samples from 1.5 to 60 ng/mL)
Accuracy (Linear Regression vs. FPIA)	Linear relationship with a reasonable slope and intercept	ACS:180 Digitoxin = 0.79 (alternate method) + 4.9 ng/mL (for 608 samples from 1.5 to 60 ng/mL)

Note: The document
does not explicitly state "acceptance criteria" values for correlation coefficient, slope, or intercept. These are inferred from the presentation of the data as supporting the device's accuracy and substantial equivalence.

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

Sample Size for Test Set: 608 samples.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's a submission to the FDA, it's highly likely to be clinical samples, though the specifics are not provided.

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

This information is not provided in the document. The "ground truth" for the test set is established by the "alternate fluorescence polarization (FPIA) method," which is itself a diagnostic assay. The document doesn't detail the development or validation of this FPIA method.

4. Adjudication Method for the Test Set

This information is not applicable/provided in the context of this type of analytical validation. The comparison is against an instrumental method (FPIA), not a human-adjudicated ground truth.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

No, an MRMC comparative effectiveness study was not done. This device is an automated immunoassay for measuring a chemical substance (digitoxin concentration) in serum/plasma, not an imaging device or a diagnostic tool requiring human interpretation or AI assistance in that sense.

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

Yes, the performance data presented is for the standalone algorithm (ACS Digitoxin immunoassay). The "accuracy" and "sensitivity" are inherent properties of the assay system itself, not dependent on human interpretation of the assay results in a "human-in-the-loop" setting.

7. The Type of Ground Truth Used

The "ground truth" (or reference method) for the performance study was an alternate fluorescence polarization (FPIA) method. This is a laboratory diagnostic method.

8. The Sample Size for the Training Set

The document does not specify a training set sample size. For an immunoassay, the "training set" concept is usually associated with the development and calibration of the assay itself, not a separate, explicitly defined "training set" as might be seen in machine learning applications. The 608 samples are described as involved in the "accuracy" study comparing to the alternate method.

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

As a "training set" is not explicitly defined or described in the context of this submission, the method for establishing its "ground truth" is not provided. The FPIA method serves as the reference standard for the performance evaluation.

Summary

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

970546

JUL 1 4 1997

Class II Digitoxin Test System, 21 CFR 862.3300

Company Confidential

Summary of Safety and Effectiveness

As required by 21 CFR 807.92, the following 510(k) Summary is provided:

1. Submitter Information

Contact person:	Thomas F. Flynn
Address:	Chiron Diagnostics Corporation63 North StreetMedfield, MA 02052
	Phone: (508) 359-3877FAX: (508) 359-3885e-mail: thomas.flynn@chirondiag.com
Date Summary Prepared:	January 31, 1997
Device Information
Proprietary Name:Common Name:	ACS DigitoxinDigitoxin Immunoassay

3. Predicate Device Information

Name:	TDX Digitoxin Immunoassay
Manufacturer:	Abbott Laboratories
510(k) Number:	Not Known

4. Device Description

Classification Name:

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

K 970546

Company Confidential

5. Statement of Intended Use

For the auantitative determination of dicitoxin in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

Summary of Technological Characteristics 6.

The Chiron Diagnostics ACS Digitoxin assay is a competitive chemiluminescent immunoassay.

7. Performance Data

Sensitivity

The ACS Digitoxin immunoassay measures digitoxin concentration up to 80 nq/mL with a minimum detectable concentration of 1 5 no/mL.

Accuracy

For 608 samples in the range of 1 5 to 60 no/mL, the correlation between the ACS:180 Digitoxin and an alternate fluorescence polarization (FPIA) method is described by the equation:

ACS:180 Digitoxin = 0.79 (alternate method) + 4.9 ng/m]

Correlation coefficient (r) = 0.83

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

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. In the center of the circle is an abstract symbol that resembles an eagle or bird in flight.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Thomas F. Flynn Manager, Regulatory Affairs & Compliance _ Chiron Diagnostics Corporation ... ........................................................................................................................................... 63 North Street Medfield, Massachusetts 02052-1688

JUL 1 4 1997

K970546 Re : ACS Diqitoxin Immunoassay Regulatory Class: II Product Code: LFM Dated: June 26, 1997 Received: June 27, 1997

Dear Mr. Flynn:

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 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, Druq, 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 Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, 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 requlation may result in regulatory In addition, FDA may publish further announcements action. 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 Requlations.

{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 requlation (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.qov/cdrh/dsmamain.html".

Sincerely yours,
Steven Ditman

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}------------------------------------------------

Page _ of _

510(k) Number (if known):

Device Name: Chiron Diagnostics ACS:180 Digitoxin Assay ____

Indications for Use:

The Chiron Diagnostics ACS:180 Digitoxin Assay is for the quantitative determination of digitoxin in serum or plasma using the Chiron ACS:180 Automated Chemiluminescence ulytoxin in Coram of placing of serum digitoxin concentrations is necessary to maintain Systementic efficacy and avoid toxicity. Serum digitoxin levels combined with other therepodite chicaly are clinician with useful information to aid in adjusting patient dosage, achieving optimal therapeutic effect, and avoiding useless subtherapeutic or harmful toxic doses.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	Ka K970546

(FLEASE DO NOT WRITE BEI.OW 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)

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.