The ACTICLOT® Protein S clotting assay is an in vitro diagnostic device intended for the quantitative determination of Protein S activity in human plasma.

Protein S activity levels in plasma are known to be low in patients with congenital Protein S deficiencies type-I, type-IIb, and type-IIb, and may also be low in pregnant I fotom & donemelers with liver disease and in inflammatory disease in which levels of C4b wonline in patients with are elevated. A decrease in Protein S activity is associated with an increased incidence of thromboembolism.

Device Description

ACTICLOT Protein S is an in vitro diagnostic clotting assay for the quantitative determination of Protein S activity in human plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the ACTICLOT® Protein S Quantitative Factor Deficiency Test, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document describes performance in relation to a predicate device and precision. While explicit, pre-defined acceptance criteria (e.g., "R-value must be greater than X") are not directly stated in the summary, the performance data implicitly serves as the basis for demonstrating substantial equivalence.

Performance Metric	Acceptance Criteria (Implicit from Predicate Equivalence)	Reported Device Performance (ACTICLOT Protein S)
Method Comparison
Linear Regression (Lot 1)	Positive correlation with predicate device	Y = 0.91X + 17.2, R = 0.868
Linear Regression (Lot 2)	Positive correlation with predicate device	Y = 1.06X - 7.5, R = 0.916
Precision
Intra-Assay CV% (Normal Control)	Low variability (implicitly acceptable)	3.0%
Inter-Assay CV% (Normal Control)	Low variability (implicitly acceptable)	5.9%
Intra-Assay CV% (Abnormal Control)	Low variability (implicitly acceptable)	2.3%
Inter-Assay CV% (Abnormal Control)	Low variability (implicitly acceptable)	5.1%

Study Details

Sample size used for the test set and the data provenance:
- Method Comparison:
  - Lot 1: n = 78 samples
  - Lot 2: n = 37 samples
- Precision: n = 80 per control sample (4 replicates over 20 runs for each of the two control levels)
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the samples are "human plasma."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This is an in vitro diagnostic device for quantitative determination of protein S activity. The performance is assessed against a predicate device and through precision measurements, not against expert human interpretation.
Adjudication method for the test set: Not applicable. See point 2.
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 not an AI-assisted diagnostic imaging or interpretation device.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The studies described are for the device (ACTICLOT Protein S) performing as an assay. This is inherently a "standalone" performance evaluation in the context of an in vitro diagnostic test, as it quantitatively determines protein S activity directly.
The type of ground truth used:
- For the method comparison, the "ground truth" is the results obtained from the predicate device (BIOCLOT Protein S-300 ACT). The ACTICLOT device's performance is compared to this established method to demonstrate substantial equivalence.
- For precision studies, the ground truth is implicitly the known concentration of the control samples.
The sample size for the training set: Not applicable. As an in vitro diagnostic assay, this device does not rely on a "training set" in the machine learning sense. Its performance is based on its chemical and biological principles and optimization of the assay reagents and protocol.
How the ground truth for the training set was established: Not applicable. See point 7.

Summary

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Section 3

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

ACTICLOT® Protein S Quantitative Factor Deficiency Test (per 21CFR864.7290)

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: K010386

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 Prepared:

July 8, 2001

Name of the Device:

ACTICLOT Protein S Product # 843L

Classification Name(s):

Factor Deficiency Test, Class II 864.7290 81GGP Test, Qualitative and Quantitative Factor Deficient

Predicate Device:

BIOCLOT Protein S-300 ACT K955738

Intended Use:

ACTICLOT Protein S is an in vitro diagnostic clotting assay for the quantitative determination of Protein S activity in human plasma.

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Summary of Substantial Equivalence:

ACTICLOT Protein S is substantially equivalent to the commercially available predicate device (BIOCLOT Protein S-300 ACT, 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 different lots of ACTICLOT Protein S. The regression statistics in Table 1 indicate a positive correlation between the ACTICLOT assay and the predicate device.

Table 1: Correlation (Y = ACTICLOT, X = predicate device)				LE MARK STATUS STATE AND STATE A BEACH AND A BEACH AND A BREAK A BALL A BEA A BALL A BEA BE A BARRET A BARRET A BARRET A BARRET A BARRET A BARRET A BARRET A BARRET A BARRET A
-----------------------------------------------------------	--	--	--	--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	--

ACTICLOTLot	n	Regression Equation	R	Sy.x(% Activity)	Sample Range(% Activity)
1	78	Y = 0.91X + 17.2	0.868	12.3	22-114
2	37	Y = 1.06X - 7.5	0.916	14.2	18-117

Precision

Precision studies evaluated intra-assay and inter-assay variability with 2 control samples run in replicates of 4 over 20 runs (n = 80 per control).

Table 2: Precision

ControlLevel	Mean(% Activity)	Intra-AssayCV%	Inter-AssayCV%
Normal	86.8	3.0	5.9
Abnormal	41.9	2.3	5.1

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or a stylized human figure, composed of three curved lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 1 4 2001

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

Re: K012386

Trade/Device Name: ACTICLOT® Protein S Regulation Number: 21 CFR 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GGP Dated: July 20, 2001 Received: July 27, 2001

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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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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/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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510(k) Notification

Section 2

STATEMENT OF INDICATIONS FOR USE

Applicant: __ American Diagnostica Inc. __

510(k) Number: _ Ko12386

Device:

Indications for Use:

The ACTICLOT® Protein S clotting assay is an in vitro diagnostic device intended for the quantitative determination of Protein S activity in human plasma.

Concurrence of CDRH, Office of Device Evaluation (ODE)

Josephine Bautista

Owision/Sign-Off) Division of Clinical Laboratory Devices

510(k) Number K012386

Regulation Number and Section

§ 864.7290 Factor deficiency test.

(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).