The SYNCHRON® Systems Digoxin (DIGN) Reagent, when used in conjunction with Beckman SYNCHRON® Systems and SYNCHRON® Systems Drug Calibrator 2 set, is intended for the quantitative determination of total digoxin in human serum or plasma on SYNCHRON® Systems.

The SYNCHRON® Systems Drug Calibrator 2, used in conjunction with SYNCHRON® Digoxin reagent, is intended for use on Beckman's SYNCHRON Systems for the calibration of Digoxin test systems.

Device Description

The SYNCHRON System Digoxin (DIGN) Reagent is designed for optimal performance on the SYNCHRON CX and LX Systems. It is intended for use in the quantitative determination of Digoxin in human serum or plasma.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the SYNCHRON® Systems Digoxin (DIGN) Reagent. This is an in-vitro diagnostic device, and the information requested (acceptance criteria, study design, etc.) is typically applied to medical devices that assist in diagnosis or treatment. The performance data provided for this diagnostic reagent focuses on method comparison and imprecision against a predicate device, which is standard for IVDs to establish substantial equivalence.

Based on the provided document, here's an analysis of the acceptance criteria and study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

For in-vitro diagnostic devices, "acceptance criteria" against a predicate device typically involve demonstrating comparable performance in terms of method comparison (correlation coefficient, slope, intercept) and precision. The document doesn't explicitly state numerical acceptance criteria, but substantial equivalence is implied if the results are "equivalent" to the predicate. The reported device performance is:

Performance Metric	SYNCHRON CX System (Serum)	SYNCHRON LX System (Serum)
Method Comparison (vs. Abbott TDx Digoxin II)
Slope	1.053	1.054
Intercept (ng/mL)	-0.03	-0.06
Correlation Coefficient (r)	0.991	0.990
Number of Samples (n)	113	112
Estimated Within-Run Imprecision
CX System
Level 1 (0.74 ng/mL)	6.96% CV
Level 2 (1.73 ng/mL)	3.29% CV
Level 3 (2.48 ng/mL)	1.80% CV
LX System
Level 1 (0.80 ng/mL)	6.06% CV
Level 2 (1.78 ng/mL)	1.78% CV
Level 3 (2.49 ng/mL)	2.62% CV

Implicit Acceptance Criteria (inferred from common IVD submission practices and the results reported):

Method Comparison: A high correlation coefficient (typically >0.97 or 0.98), a slope close to 1 (e.g., between 0.95 and 1.05), and an intercept close to 0 (e.g., within a clinically acceptable range for the analyte) compared to the predicate device. The reported values of r=0.991 and 0.990, slopes of 1.053 and 1.054, and intercepts of -0.03 and -0.06 strongly suggest these criteria were met.
Imprecision: Within-run Coefficient of Variation (CV) values that are deemed acceptable for the assay and analyte, and ideally comparable to or better than the predicate. The reported CVs (1.80% - 6.96%) are generally considered good for a quantitative immunoassay.

2. Sample sized used for the test set and the data provenance

Sample Size for Test Set:
- Method Comparison: 113 samples for the SYNCHRON CX System and 112 samples for the SYNCHRON LX System. These samples were human serum.
- Imprecision (for each level): 80 samples each for Levels 1, 2, and 3 on both CX and LX systems, totaling 240 samples per system for imprecision assessment.
Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. It only states the samples were "human serum" or "human serum or plasma" in the intended use.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This question is not directly applicable in the typical sense for an in-vitro diagnostic reagent like this. The "ground truth" for a quantitative analyte such as Digoxin is established by a reference method or a predicate device that is already FDA-cleared and considered accurate.

In this case, the predicate device, Abbott TDx Digoxin II, served as the comparative method against which the new device's measurements were compared. The "ground truth" measurements for the method comparison were obtained using this predicate device. This is a common approach for demonstrating substantial equivalence for IVDs.
No human experts were used to "establish ground truth" in the way one might for image interpretation or disease diagnosis.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable. This is not a study involving human interpretation or subjective assessment that would require an adjudication method. The comparison is between two quantitative analytical instruments.

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

Not applicable. This is an in-vitro diagnostic device, not an AI-powered diagnostic imaging or interpretation system. There are no "human readers" in the context of this submission, nor is there AI assistance involved.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, in the context of an IVD, the "standalone performance" is precisely what was evaluated. The SYNCHRON Digoxin Reagent, when run on the SYNCHRON CX and LX Systems, generates a quantitative result without direct human interpretation of the measurement itself (though a human interprets the quantitative value in a clinical context). The method comparison and imprecision studies demonstrate the performance of the device itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the test set was effectively established by the predicate device, the Abbott TDx Digoxin II system. The new device's performance was evaluated against the measurements obtained from this legally marketed and accepted predicate method.

8. The sample size for the training set

The document does not specify a "training set" sample size. For an IVD reagent, method development involves internal studies and optimization, but the 510(k) submission generally focuses on the validation (test set) data demonstrating equivalence to a predicate. The reported sample sizes (112-113 for method comparison, 80 per level for imprecision) are for the validation/test studies.

9. How the ground truth for the training set was established

Not explicitly stated or applicable in the sense of a machine learning "training set" with ground truth labels. For the development of the reagent, the "ground truth" for optimizing its performance would have been established through internal validation using reference methods, established standards, or comparisons to existing assays during the development phase. The 510(k) focuses on the final performance validation against a predicate.

Summary

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

1 1 4 100

K982935

Image /page/0/Picture/2 description: The image shows the logo for Beckman Coulter. The logo consists of a stylized black circle on the left, with two curved white lines running through it. To the right of the circle is the company name, "BECKMAN COULTER," written in bold, black, sans-serif font. The word "BECKMAN" is stacked on top of the word "COULTER."

Summary of Safety & Effectiveness SYNCHRON® Systems Digoxin (DIGN) Reagent

1.0 Submitted By:

Lucinda Stockert Staff Regulatory Specialist, Product Submissions Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-104 Brea, California 92822-8000 Telephone: (714) 961-3777 FAX: (714) 961-4123

2.0 Date Submitted:

August 19, 1998

3.0 Device Name(s):

3.1 Proprietary Names

SYNCHRON® Systems Digoxin (DIGN) Reagent SYNCHRON® Systems Drug Calibrator 2

Classification Name 3.2

Digoxin (21CFR §862.3320) Calibrator (21 CFR §862.3200)

4.0 Predicate Device(s):

SYNCHRON SystemsReagent	Predicate	Manufacturer	DocketNumber
SYNCHRON®Systems Digoxin(DIGN)	TDx®** Digoxin II	Abbott* Laboratories,Inc	K882233

*Abbott Laboratories, Abbott Park, IL 60064 **Trademark of Abbott Laboratories

5.0 Description:

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

6.0 Intended Use:

The SYNCHRON® Systems Digoxin (DIG) Reagent, when used in conjunction with Beckman SYNCHRON® Systems and SYNCHRON® Systems Drug Calibrator 2 set, is intended for the quantitative determination of total digoxin in human serum or plasma on SYNCHRON® Systems.

The SYNCHRON® Systems Drug Calibrator 2, used in conjunction with SYNCHRON® Digoxin reagent, is intended for use on Beckman's SYNCHRON Systems for the calibration of Digoxin test systems.

7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary.

	SIMILARITIES
SYNCHRON®Systems Digoxin(DIGN)	Intended use.	Same as Abbott TDxDigoxin II Reagent
	Liquid stable reagents.Multipoint Calibration SchemeReagent measures digoxin inboth human plasma andserum samples
	DIFFERENCES
SYNCHRON®Systems Digoxin(DIGN)	SYNCHRON DIGN utilizesturbidimetric inhibitionimmunoassay	Abbott TDx Digoxin reagentutilizes fluorescencepolarization immunoassay
	Antibody source forSYNCHRON DIGN is mouse.	Antisera source for TDxDigoxin II is rabbit.
	Sample Pretreatment	SYNCHRON Systems DIGNdoes not require samplepretreatment while thepredicate requires samplepretreatment

8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, and imprecision experiments.

SYNCHRONDIGN Reagent	SampleType	Slope	Intercept(ng/mL)	r	n	PredicateMethod
SYNCHRONCX System	serum	1.053	-0.03	0.991	113	Abbott TDxDigoxin II
SYNCHRONLX System	serum	1.054	-0.06	0.990	112	Abbott TDxDigoxin II

Method Comparison Study Results

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

SYNCHRONSystem	Sample	Mean(ng/mL)	S.D. (ng/mL)	%C.V.	N
	Level 1	0.74	0.05	6.96	80
CX	Level 2	1.73	0.06	3.29	80
	Level 3	2.48	0.05	1.80	80
	Level 1	0.80	0.05	6.06	80
LX	Level 2	1.78	0.03	1.78	80
	Level 3	2.49	0.07	2.62	80

Estimated Within-Run Imprecision

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like figure composed of three human profiles facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the emblem.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 1 4 1998

Lucinda Stockert . Staff Regulatory Specialist Beckman Coulter, Inc. 200 S. Kraemer Boulevard, M/S W-104 P.O. Box 8000 Brea, California 92822-8000

Re : K982935 SYNCHRON® Systems Digoxin Reagent Requlatory Class: II Product Code: KXT, DLJ Dated: August 19, 1998 Received: August 21, 1998

Dear Ms. Stockert:

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, 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 Requlations, Title 21, Parts 800 to 895. ਕੇ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set torth 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.

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

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/dsmamain.html".

Sincerely yours,
Steven Sitman

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

{5}------------------------------------------------

page of

510(k) Number (if known)

510(k) Number (if known):

Device Name: SYNCHRON® Systems Digoxin (DIGN) Reagent

Indications for Use:

The SYNCHRON® Systems Drug Calibrator 2, used in conjunction with SYNCHRON® Digoxin reagent, is intended for use on Beckman's SYNCHRON Systems for the calibration of Digoxin test systems.

Clinical Significance:

Digoxin is administered for conditions of heart failure or in the treatment of certain Digoxin therapy is monitored for possible toxicity and cardiac arrhythmias. inadequate therapeutic response.

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

Concurrence of CDRH, Office of Device Evaluation (ODE) (Division Sign-Off Division of Clinical Laboratory D 510(k) Number. Prescription Use OR Over-the-Counter Use (per 21 CFR 801.109) Optional Format 1-2-96

Regulation Number and Section

§ 862.3320 Digoxin test system.

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