The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurements and calculated parameters.

Device Description

AI/ML Overview

This document describes the ACL TOP, an automated coagulation analyzer, and presents data to support its substantial equivalence to a predicate device, the ACL Advance.

1. Acceptance Criteria and Reported Device Performance:

The primary acceptance criteria for the ACL TOP are based on demonstrating substantial equivalence to the predicate device, the ACL Advance, through method comparison. This is achieved by showing statistical similarity between the measurements obtained by both devices for various coagulation parameters.

Reagent Type	Performance Metric (ACL TOP vs. ACL Advance)	Reported Device Performance	Acceptance Criteria (Implied by Predicate Equivalence)
Antithrombin (%)	Slope	1.03	Slope close to 1.0
	Intercept	-1.418	Intercept close to 0.0
	Correlation Coefficient (r)	0.9660	Acceptably high correlation (e.g., >0.95 or similar to predicate's known performance)
APTT (Seconds)	Slope	1.076	Slope close to 1.0
	Intercept	-0.380	Intercept close to 0.0
	Correlation Coefficient (r)	0.9943	Acceptably high correlation
D-Dimer (ng/mL)	Slope	1.12	Slope close to 1.0
	Intercept	-16.0	Intercept close to 0.0
	Correlation Coefficient (r)	0.993	Acceptably high correlation
Factor II (%)	Slope	0.95	Slope close to 1.0
	Intercept	-0.551	Intercept close to 0.0
	Correlation Coefficient (r)	0.9753	Acceptably high correlation
Factor V (%)	Slope	0.81	Slope close to 1.0
	Intercept	4.742	Intercept close to 0.0
	Correlation Coefficient (r)	0.9822	Acceptably high correlation
Factor VII (%)	Slope	0.88	Slope close to 1.0
	Intercept	3.153	Intercept close to 0.0
	Correlation Coefficient (r)	0.9922	Acceptably high correlation
Factor X (%)	Slope	0.97	Slope close to 1.0
	Intercept	2.995	Intercept close to 0.0
	Correlation Coefficient (r)	0.9954	Acceptably high correlation
Fibrinogen-C (mg/dL)	Slope	1.00	Slope close to 1.0
	Intercept	-8.740	Intercept close to 0.0
	Correlation Coefficient (r)	0.9759	Acceptably high correlation
Protein C (%)	Slope	1.15	Slope close to 1.0
	Intercept	-0.323	Intercept close to 0.0
	Correlation Coefficient (r)	0.9902	Acceptably high correlation
Prothrombin Time (PT) (Seconds)	Slope	0.990	Slope close to 1.0
	Intercept	1.46	Intercept close to 0.0
	Correlation Coefficient (r)	0.9987	Acceptably high correlation
PT-Based Fibrinogen (mg/dL)	Slope	1.084	Slope close to 1.0
	Intercept	-9.93	Intercept close to 0.0
	Correlation Coefficient (r)	0.9587	Acceptably high correlation
Precision			Percentage Coefficient of Variation (%CV) within acceptable clinical limits, and comparable to the predicate device's known precision. (No explicit numerical acceptance criteria are stated, but the reported values show good precision).
Antithrombin (%)	Within Run %CV	Normal: 5.7, Low Abnormal: 5.6, High Abnormal: 6.8
	Total %CV	Normal: 5.8, Low Abnormal: 6.8, High Abnormal: 9.1
APTT (Seconds)	Within Run %CV	Normal: 1.2, Low Abnormal: 0.9, High Abnormal: 0.9
	Total %CV	Normal: 1.6, Low Abnormal: 2.1, High Abnormal: 1.4
D-Dimer (ng/mL)	Within Run %CV	Low Control: 4.6, High Control: 2.5
	Total %CV	Low Control: 7.7, High Control: 4.5
... (and so on for all listed reagents, similar precision metrics apply)

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Test Set Sample Size:
- Antithrombin: n=123 (method comparison), n=80 (precision)
- APTT: n=205 (method comparison), n=80 (precision)
- D-Dimer: n=120 (method comparison), n=80 (precision)
- Factor II: n=101 (method comparison), n=80 (precision)
- Factor V: n=93 (method comparison), n=80 (precision)
- Factor VII: n=96 (method comparison), n=80 (precision)
- Factor X: n=110 (method comparison), n=80 (precision)
- Fibrinogen-C: n=98 (method comparison), n=80 (precision)
- Protein C: n=123 (method comparison), n=80 (precision)
- Prothrombin Time (PT): n=150 (method comparison), n=80 (precision)
- PT-Based Fibrinogen: n=93 (method comparison), n=80 (precision)
Data Provenance: The document states "in-house performance data" and "method comparison studies evaluating citrated plasma samples." It does not specify the country of origin of the data or whether the study was retrospective or prospective. However, given the context of a 510(k) summary for an in vitro diagnostic device, it is highly likely that these were prospective studies conducted in a laboratory setting. The samples were "citrated plasma samples," which are common for coagulation testing.

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

The concept of "ground truth" as typically used for AI/ML devices (e.g., expert consensus, pathology, outcomes data) does not directly apply here. For an in vitro diagnostic device like the ACL TOP, the "ground truth" for the method comparison study is implicitly established by the measurements obtained from the predicate device (ACL Advance). The predicate device itself has been cleared by the FDA and its performance characteristics are accepted as a standard against which the new device is compared. Similarly, for precision studies, the "ground truth" is the true analytical variability inherent to the control materials or samples used.

There is no mention of external human experts establishing ground truth for these types of analytical performance studies; the focus is on the analytical agreement between the new device and the predicate device.

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

Not applicable. Adjudication methods are typically employed in studies where human interpretation of medical images or data is being evaluated, often to resolve discrepancies between readers or between human readers and an AI algorithm. For an in vitro diagnostic instrument like the ACL TOP, the performance is assessed through quantitative measurements and statistical comparison against a predicate device, rather than subjective interpretations requiring adjudication.

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. An MRMC study is relevant for diagnostic imaging AI/CAD systems that assist human readers in tasks like lesion detection or diagnosis. The ACL TOP is an automated laboratory instrument measuring coagulation parameters; it does not involve human readers interpreting AI output.

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

Yes, the studies presented are effectively standalone performance evaluations. The ACL TOP is a "fully automated, random access analyzer" and its performance data (precision and method comparison) reflects the device operating independently to produce results. There is no human-in-the-loop component described for its basic operation or for these performance studies, other than potentially loading samples and controls. The method comparison directly compares the ACL TOP's measurements to those of the predicate device (ACL Advance), with both devices acting in a standalone capacity.

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

The "ground truth" for the method comparison study is the analytical results generated by the predicate device, ACL Advance. For precision data, the ground truth is the inherent variability of the controls and samples, which is quantified by statistical measures like %CV. This is an analytical rather than a clinical ground truth.

8. The sample size for the training set

Not applicable. The ACL TOP is an automated analyzer, not an AI/ML device that requires a "training set" in the conventional sense of machine learning. Its operation is based on established analytical principles for coagulation testing, calibrated using standard laboratory calibration materials, not trained on a dataset.

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

Not applicable, as there is no "training set" for an AI/ML algorithm. Calibration and quality control for such instruments typically involve using reference materials with known concentrations or activities, established by manufacturers or regulatory bodies, to ensure accurate measurement.

Summary

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KQ33414

JAN 1 2 2004

Section 3 ACL TOP - 510(k) Summary (Summary of Safety and Effectiveness)

Submitted by:

Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421 Phone: 781-861-4467 781-861-4207 Fax:

Contact Person:

Carol Marble, Regulatory Affairs Director Phone: 781-861-4467 / Fax: 781-861-4207

Summary Prepared:

October 24, 2003

Name of the Device:

ACL TOP

Classification Name(s):

81GKP864.5400	Instrument, Coagulation, AutomatedCoagulation Instrument	Class II
81JPA864.5425	System, Multipurpose for In Vitro Coagulation StudiesMultipurpose system for In Vitro Coagulation Studies	Class II

Identification of predicate device(s):

K002400 ACL Advance

Description of the device/intended use(s):

The system provides results for both direct hemostasis measurements and calculated parameters.

Statement of Technological Characteristics of the Device Compared to Predicate Device:

The ACL TOP is substantially equivalent in performance, intended use, safety and effectiveness to the ACL Advance (predicate device) for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis.

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Section 3 (Cont.) ACL TOP - 510(k) Summary (Summary of Safety and Effectiveness)

Summary of Performance Data:

Precision

Within run and total precision assessed over multiple runs (n=80) using normal and abnormal levels of control plasma gave the following results:

Reagent Type	Control Level	Mean	Within Run%CV	Total%CV
Antithrombin(%)	Normal	108.5	5.7	5.8
	Low Abnormal	53.5	5.6	6.8
	High Abnormal	32.0	6.8	9.1
APTT(Seconds)	Normal	30.3	1.2	1.6
	Low Abnormal	49.3	0.9	2.1
	High Abnormal	59.0	0.9	1.4
D-Dimer(ng/mL)	Low Control	340	4.6	7.7
	High Control	729	2.5	4.5
Factor II(%)	Normal	110.7	4.2	5.2
	Low Abnormal	64.5	4.1	5.3
	High Abnormal	37.5	3.8	5.6
Factor V(%)	Normal	124.7	4.0	4.7
	Low Abnormal	79.9	3.0	4.7
	High Abnormal	43.4	3.6	4.8
Factor VII(%)	Normal	106.2	3.6	3.9
	Low Abnormal	61.3	2.1	3.7
	High Abnormal	33.0	2.9	4.4
Factor X(%)	Normal	114.6	1.8	2.8
	Low Abnormal	64.6	2.2	3.4
	High Abnormal	38.3	1.9	3.6
Fibrinogen-C(mg/dL)	Normal	364.7	7.9	8.8
	Low Fibrinogen	92.9	7.7	8.4
Protein C(%)	Normal	120.4	2.6	3.3
	Low Abnormal	30.9	3.0	4.3
	High Abnormal	18.4	3.7	4.7
Prothrombin Time (PT)(Seconds)	Normal	11.9	1.3	1.4
	Low Abnormal	25.7	1.5	2.7
	High Abnormal	37.3	1.8	3.0
PT-Based Fibrinogen(mg/dL)	Normal	302.6	3.7	4.1
	Low Fibrinogen	128.2	7.7	7.8

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Section 3 (Cont.) ACL TOP - 510(k) Summary (Summary of Safety and Effectiveness)

Summary of in-house performance data (Cont.):

Method Comparison

In method comparison studies evaluating citrated plasma samples, the ACL TOP and the ACL Advance (predicate device) were shown to be statistically similar as shown below.

Reagent Type	n	Slope	Intercept	r	Sample Range
Antithrombin(%)	123	1.03	-1.418	0.9660	25.0 to 121.7
APTT(Seconds)	205	1.076	-0.380	0.9943	24.2 to 236.7
D-Dimer(ng/mL)	120	1.12	-16.0	0.993	84 to 19809
Factor II(%)	101	0.95	-0.551	0.9753	6.0 to 128.2
Factor V(%)	93	0.81	4.742	0.9822	2.1 to 149.3
Factor VII(%)	96	0.88	3.153	0.9922	6.3 to 147.4
Factor X(%)	110	0.97	2.995	0.9954	5.0 to 142.3
Fibrinogen-C(mg/dL)	98	1.00	-8.740	0.9759	121.6 to 695.0
Protein C(%)	123	1.15	-0.323	0.9902	9.4 to 129.7
Prothrombin Time (PT)(Seconds)	150	0.990	1.46	0.9987	9.8 to 107.4
PT-Based Fibrinogen(mg/dL)	93	1.084	-9.93	0.9587	121.6 to 695.0

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Indications for Use Statement

510(k) Number (if known): K033414

Device Name: ACL TOP

Indications for Use:

The system provides results for both direct hemostasis measurements and calculated parameters.

(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 801.019) OR Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

Section 2

ACL TOP Abbreviated 510(k)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. 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 bird in flight, composed of three curved lines.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 1 2 2004

Ms. Carol Marble Regulatory Affairs Director Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421

K033414 Re: Trade/Device Name: ACL TOP Regulation Number: 21 CFR 864.5400 Regulation Name: Coagulation instrument Regulatory Class: Class II Product Code: GKP Dated: October 24, 2003 Received: October 27, 2003

Dear Ms. Marble:

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 it into of our of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may outlish 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 complics with other requirements of the Act than a Dederal statutes and regulations administered by other Federal agencies. You must or unry vith all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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 Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): K033414

Device Name: ACL TOP

Indications for Use:

The system provides results for both direct hemostasis measurements and calculated parameters.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K033414

Prescription Use
(Per 21 CFR 801.019)

Over-The-Counter Use _

Section 2

ACL TOP Abbreviated 510(k)

Page 1 of

Regulation Number and Section

§ 864.5400 Coagulation instrument.

(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.