ACTICHROME® Heparin (anti-fXa) is a chromogenic assay intended for the quantitative determination of unfractionated and low molecular weight heparins in human plasma. The assay measures the inhibition of factor Xa (fXa) activity by the various heparins. The Electra 900C® was used to determine performance data. This kit is for in vitro diagnostic use.

Device Description

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the ACTICHROME® Heparin (anti-fXa) device:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve an R-value of at least X"). Instead, it presents performance data and implies that equivalence to the predicate device is the overarching acceptance criterion. Thus, the "acceptance criteria" are inferred from the demonstrated performance in comparison to the predicate.

Acceptance Criteria (Inferred from Predicate Equivalence)	Reported Device Performance (ACTICHROME Heparin (anti-fXa))
Method Comparison vs. Predicate Device
Positive correlation with predicate device (implied R > 0.8)	Unfractionated Heparin (Lot 007): R = 0.913, Y = 0.843X + 0.003, Sy.x = 0.07
	Unfractionated Heparin (Lot 010): R = 0.859, Y = 0.765X - 0.009, Sy.x = 0.08
	LMW Heparin (Lot 010): R = 0.895, Y = 1.363X - 0.139, Sy.x = 0.14
Precision (Intra-Assay CV%)
Maintain low intra-assay variability (implied < 10%)	Lot 007, Control 6: 3.3%
	Lot 007, Control 3: 5.6%
	Lot 010, 0.5 U/ml UFH: 2.8%
	Lot 010, 0.25 U/ml UFH: 3.6%
	Lot 010, 0.5 U/ml LMWH: 2.9%
	Lot 010, 0.25 U/ml LMWH: 5.1%
Precision (Inter-Assay CV%)
Maintain low inter-assay variability (implied < 15%)	Lot 007, Control 6: 4.1%
	Lot 007, Control 3: 4.8%
	Lot 010, 0.5 U/ml UFH: 4.6%
	Lot 010, 0.25 U/ml UFH: 10.6%
	Lot 010, 0.5 U/ml LMWH: 6.2%
	Lot 010, 0.25 U/ml LMWH: 9.3%
Substantial Equivalence	Declared "substantially equivalent to the commercially available ACTICHROMIS Hopanin (and Tra) in Is ourin (Xa), manufactured by Biopool International, Ventura, CA, in performance and intended use."

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

The text describes method comparison studies and precision studies which serve as the test set for device performance.

Method Comparison (Test Set):
- Lot 007 (unfractionated Heparin): N = 92 samples
- Lot 010 (unfractionated Heparin): N = 40 samples
- Lot 010 (LMW Heparin): N = 42 samples
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). It mentions "human plasma" but no further detail.
Precision (Test Set Control Samples):
- Lot 007: 2 control samples run in quadruplicate over 20 runs (N = 80 per control, total 160 measurements).
- Lot 010: 2 control samples run in quadruplicate over 10 runs (N = 40 per control, total 80 measurements).
- Data Provenance: Not explicitly stated. The samples are described as "control samples" and "Control Plasma spiked with..."

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

This device is a chromogenic assay for quantitative determination of heparins. The "ground truth" for such assays is typically established by comparing against a reference method (the predicate device in this case) and assessing analytical performance like precision and accuracy, not by human expert consensus on interpretations. Therefore, the concept of "experts establishing ground truth" as it applies to image analysis or diagnostic interpretation by radiologists, for example, is not relevant here.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative assay whose performance is assessed against a predicate device and through precision studies, not requiring human adjudication of results in the way a diagnostic interpretation might.

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

No, an MRMC comparative effectiveness study was not done. This type of study assesses human reader performance, often with and without AI assistance, which is not relevant for a quantitative diagnostic assay like the ACTICHROME® Heparin (anti-fXa) kit.

6. Standalone (Algorithm Only) Performance Study

Yes, the performance data presented (method comparison and precision) represent the standalone performance of the ACTICHROME® Heparin (anti-fXa) assay. It measures the assay's capability to quantify heparin levels. There is no "human-in-the-loop" aspect to its intended use or performance evaluation described.

7. Type of Ground Truth Used

The "ground truth" for this study is essentially the measurement provided by the predicate device for the method comparison, and known concentrations in control samples for the precision studies. It is based on established analytical methods and reference materials, rather than expert consensus, pathology, or outcomes data.

8. Sample Size for the Training Set

The text describes performance studies (method comparison and precision), not a machine learning study with explicit training and test sets in the AI sense. Therefore, there is no specified "training set" for the algorithm itself (as a traditional assay does not have an algorithm that is "trained"). The phrase "training set" typically refers to data used to develop and optimize an AI model. This device is a chromogenic assay kit.

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

Not applicable as there is no "training set" in the context of an AI algorithm. The device is a chemical assay, and its development would involve standard analytical chemistry and immunoassay development processes to optimize its reagents and protocols.

Summary

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Section 3

8 2002 MAR

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

ACTICHROME® Heparin (anti-fXa) Heparin Assay (per 21CFR864.7525)

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K013318

Submitted by:

American Diagnostica Inc. 222 Railroad Avenue Greenwich, CT 06830 Phone: 203 661-0000 Fax: 203 661-7784

Contact:

Clare Santulli Field Trial Coordinator Phone: 203 661-0000

Summary Revised:

February 26, 2002

Name of the Device:

ACTICHROME® Heparin (anti-fXa) Product No. 832

Classification:

Heparin Assay, Class II 864.7525 Product Code KFF

Predicate Device:

Spectrolyse® Heparin (Xa) K923499

Intended Use:

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Summary of Substantial Equivalence:

ACTICHROME Heparin (anti-fXa) kit is substantially equivalent to the commercially available ACTICHNOMIS Hopanin (and Tra) in Is ourin (Xa), manufactured by Biopool International, Ventura, CA, in performance and intended use.

Summary of Performance Data:

Method Comparison

Method comparison studies versus the predicate device were performed with two lots of ACTICHROME Heparin (anti-fXa). The regression statistics in Table 1 indicate a positive correlation between the ACTICHROME Heparin (anti-fXa) assay and the predicate device.

ACTICHROMEHeparin (anti-fXa)	N	Regression Equation	R	Sy.x(ng/ml)	Sample Range(ng/ml)
Lot 007 (unfractionated Heparin)	92	$Y=0.843X+0.003$	0.913	0.07	0.01-0.8
Lot 010 (unfractionated Heparin)	40	$Y=0.765X--0.009$	0.859	0.08	0.00-0.8
Lot 010 (LMW Heparin)	42	$Y=1.363X--0.139$	0.895	0.14	0.30-1.3

Table 1: Correlation (Y= ACTICHROME, X= predicate device)

Precision

Lot 007 precision studies evaluated intra-assay and inter-assay variability with 2 control samples run in quadruplicate over 20 runs (N = 80 per control). Lot 010 evaluated intra-assay and inter-assay variability with 2 control samples run in quadruplicate over 10 runs (N = 40 per control). Lot 010 evaluated unfractionated heparin and low molecular weight heparin. The results are provided in Tables 2a and 2b.

Table 2a: Precision using unfractionated heparin

ACTICHROMEHeparin (anti-fXa)Lot 007	Mean(U/ml)	Intra-AssayCV%	Inter-AssayCV%
Hepanorm Control 6	0.44	3.3	4.1
Hepanorm Control 3	0.25	5.6	4.8

Table 2b: Precision using unfractionated heparin and low molecular weight heparin

ACTICHROMEHeparin (anti-fXa) Lot 010
	Mean(U/ml)	Intra-AssayCV%	Inter-AssayCV%
Control Plasma spiked with 0.5 U/ml UFH Heparin	0.51	2.8	4.6
Control Plasma spiked with 0.25 U/ml UFH Heparin	0.22	3.6	10.6
Control Plasma spiked with 0.5 U/ml LMW Heparin	0.48	2.9	6.2
Control Plasma spiked with 0.25 U/ml LMW Heparin	0.24	5.1	9.3

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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 consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 8 2002

Mr. John Berryman Director of Regulatory Affairs American Diagnostica Inc. 222 Railroad Avenue Greenwich, CT 06830

K013318 Re:

Trade/Device Name: ACTICHROME® Heparin (anti-fXa) Regulation Number: 21 CFR 864.7525 Regulation Name: Heparin assay Regulatory Class: Class II Product Code: KFF Dated: February 26, 2002 Received: February 27, 2002

Dear Mr. Berryman:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket I his letter will and in you all stantial equivalence of your device to a legally marketed noutheation. The I Dr I mining of exceion 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 1 II you desire spoonly active diagnostic devices), please contact the Office of Compliance at additionally 607.10 for in in the promotion and advertising of your device, (301) 594-4566. Traditional Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small nuoufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or 1301) 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

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Section 2

STATEMENT OF INDICATIONS FOR USE

Applicant: ___ American Diagnostica Inc.

510(k) Number: _______________________________________________________________________________________________________________________________________________________________

Device: ACTICHROME® Heparin (anti-fXa) ____

Indications for Use:

This kit is for in vitro diagnostic use.

Concurrence of CDRH, Office of Device Evaluation (ODE)

Arphini Bautista

510(k) Number K01331

Regulation Number and Section

§ 864.7525 Heparin assay.

(a)
Identification. A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).(b)
Classification. Class II (performance standards).