Spectrolyse ® PAI-1 kit, Product # 101201, is intended for the quantitative determination of Plasminogen Activator Inhibitor Type-1 (PAI-1) activity in human plasma. The test is for in vitro diagnostic use and is not intended for internal use in humans and animals.

Device Description

Spectrolyse @ PAI-1 is a two stage colorimetric assay. The first stage involves incubating samples with a known amount of tPA, allowing PAI-1 in the sample to react with tPA. In the second stage, the residual tPA activity converts plasminogen to plasmin, which in turn hydrolyzes a plasmin chromogenic substrate, SPECTROZYME® PL. PAI-1 in the plasma is determined as the difference between the amount of tPA added and the amount of tPA recovered.

AI/ML Overview

Analysis of Spectrolyse® PAI-1 Device Performance

This document describes the acceptance criteria and the supporting study for the Spectrolyse® PAI-1 Quantitative Factor Deficiency Test (Product #101201).

1. Table of Acceptance Criteria and Reported Device Performance

The device sought substantial equivalence to a predicate device in terms of performance and intended use. The primary performance metric evaluated was the correlation with the predicate device. Precision (intra-assay and inter-assay variability) was also assessed.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Correlation	Positive correlation (R value close to 1, slope close to 1, intercept close to 0) with the predicate device.	Study 1: N=34, Regression Equation: Y=1.0787X+-4.76, R=0.953, Sy.x=3.31 ng/ml (Sample Range: 5.3-37.8 ng/ml) Study 2: N=34, Regression Equation: Y=1.0179X+-3.75, R=0.955, Sy.x=2.65 ng/ml (Sample Range: 5.0-42.3 ng/ml)
Precision	Low intra-assay and inter-assay Coefficients of Variation (CV%) for control samples.	Study #1: Control 1 (Mean 10.4 IU/mL): Intra-Assay CV% = 3.6%, Inter-Assay CV% = 12.9% Control 2 (Mean 13.8 IU/mL): Intra-Assay CV% = 3.4%, Inter-Assay CV% = 7.5% Control 3 (Mean 22.2 IU/mL): Intra-Assay CV% = 2.4%, Inter-Assay CV% = 3.9% Study #2: Control 1 (Mean 6.7 IU/mL): Intra-Assay CV% = 14.4%, Inter-Assay CV% = 10.2% Control 2 (Mean 14.4 IU/mL): Intra-Assay CV% = 3.5%, Inter-Assay CV% = 5.7% Control 3 (Mean 26.0 IU/mL): Intra-Assay CV% = 2.0%, Inter-Assay CV% = 4.1%

Note: The document implies acceptance criteria by stating that the device is "substantially equivalent" to a predicate device based on these performance metrics. Specific numerical cut-offs for R, slope, intercept, and CV% are not explicitly provided as 'acceptance criteria' in the text, but the reported values support the claim of substantial equivalence.

2. Sample Size and Data Provenance for the Test Set

Sample Size for Test Set:
- Method Comparison Studies: 34 samples per study. (Total of 68 unique samples if the two studies used different sets, or 34 if they used the same samples analyzed with two different lots). The text states "two lots of Spectrolyse® PAI-1" were used across "two method comparison studies," suggesting that each study potentially involved the same set of 34 samples tested with a different lot, or two distinct sets of 34 samples.
- Precision Studies: Not applicable to patient samples for ground truth. Control samples (3 different concentrations) were used. In Study #1, controls were run in replicates of 4 over 20 runs (N=40 per control). In Study #2, controls were run in replicates of 4 over 5 runs (N=10 per control).
Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given the context of a 510(k) submission for an in vitro diagnostic, it is generally assumed to be prospective or recent retrospective data collected typically in a clinical laboratory setting, likely within the US, but this is not confirmed.

3. Number of Experts and Qualifications for Ground Truth

Number of Experts: Not applicable. For quantitative diagnostic tests like this, 'ground truth' for patient samples is established by comparison to a reference method (the predicate device) or a gold standard assay, not by expert consensus on visual interpretation or clinical judgment.
Qualifications of Experts: Not applicable.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The "ground truth" for method comparison was the result obtained from the predicate device, which is an established quantitative assay. There was no need for expert adjudication.

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

Was an MRMC study done? No. This device is a quantitative in vitro diagnostic (IVD) assay designed to measure a specific analyte (PAI-1 activity) in human plasma. It does not involve human readers interpreting images or data in a way that would necessitate an MRMC comparative effectiveness study to assess improvement with AI assistance. The device operates independently of human interpretive input in its primary function.

6. Standalone Performance Study

Was a standalone study done? Yes. The entire submission focuses on the standalone performance of the Spectrolyse® PAI-1 device. The method comparison studies directly compare the performance of the Spectrolyse® PAI-1 device (algorithm/assay only) against the predicate device. The precision studies also evaluate the Spectrolyse® PAI-1 device in isolation. "Standalone" performance here refers to the device's ability to produce quantitative results for PAI-1 activity.

7. Type of Ground Truth Used

Type of Ground Truth: The "ground truth" for the method comparison studies was the quantitative result obtained from the predicate device, Spectrolyse® /pL PAI (manufactured by BIOPOOL, K922782). This is a comparison against an existing, legally marketed diagnostic assay. For the precision studies, the ground truth was the expected value of the control samples.

8. Sample Size for the Training Set

Sample Size for Training Set: The document does not explicitly mention a "training set" in the context of machine learning or AI development. This is a traditional IVD device, not an AI-based diagnostic tool. The development process would have involved internal optimization and validation studies, but these are not typically referred to as a "training set" in this regulatory context.

9. How Ground Truth for the Training Set Was Established

How Ground Truth for Training Set Was Established: Not applicable, as there is no explicitly defined "training set" for an AI algorithm. The device's operational parameters and calibration would have been established using reference materials and established laboratory methods during its development phase.

Summary

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Revised Section 3 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Spectrolyse 9 PAI-1 Quantitative Factor Deficiency Test (per 21CFR864.7290)

Act 1 5 2007

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: K063323

Submitted by:

American Diagnostica Inc. 500 West Avenue Stamford, CT 06902 Tel. 203 602-7777 Fax 203 602-2221

Contact:

Jodi Radassao Clare Santulli Field Trial Personnel Phone: 203 602-7777 x25

Summary Prepared:

July 27, 2007

Name of the Device:

Spectrolyse ® PAI-1 Product No. 101201

Classification Name(s):

864.7290 Test, Qualitative And Quantitative Factor Deficiency GGP Hematology Reagents, Class II

Predicate Device:

Spectrolyse/pL PAI K922782

Description of the Device

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Intended Use:

Spectrolyse ® PAI-1, Product # 101201, is intended for the quantitative determination of Plasminogen Activator Inhibitor Type-1 (PAI-1) activity in human plasma. The test is for in vitro diagnostic use and is not intended for internal use in humans and animals.

Summary of Substantial Equivalence:

Spectrolyse ® PAI, Product # 101201 is substantially equivalent to the commercially available predicate device Spectrolyse® /pL PAI manufactured by BIOPOOL in performance and intended use.

Summary of Performance Data:

Method Comparison

Two method comparison studies versus the predicate device were performed with two lots of Spectrolyse® PAI-1. The regression statistics in Table 1 indicate a positive correlation between the Spectrolyse® PAI-1 assay and the predicate device.

	N	RegressionEquation	R	Sy.x(ng/ml)	Sample Range(ng/ml)
Study 1	34	Y=1.0787X+-4.76	0.953	3.31	5.3-37.8
Study 2	34	Y=1.0179X+-3.75	0.955	2.65	5.0-42.3

Table 1: Correlation (Y=subject device. X=predicate device)

Precision

Precision studies evaluated intra-assay and inter-assay variability with 3 control samples. In Study #1 control samples were run in replicates of 4 over 20 runs (N=40 per control). In Study #2 control samples were run in replicates of 4 over 5 runs (N= 10 per control). Assay results (IU/mL) were calculated using duplicate determinations. Two lots were evaluated.

	Table 2: Precision

	Mean(IU/mL)	Intra-AssayCV%	Inter-AssayCV%
Control 1	10.4	3.6	12.9
Control 2	13.8	3.4	7.5
Control 3	22.2	2.4	3.9

Table 3: Precision

	Mean(IU/mL)	Intra-AssayCV%	Inter-AssayCV%
Control 1	6.7	14.4	10.2
Control 2	14.4	3.5	5.7
Control 3	26.0	2.0	4.1

American Diagnostica, Inc.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 1 5 2007

American Diagnostica, Inc. C/O David Teicher 500 West Avenue Stamford, Connecticut 06902

Re: K063323

Trade/Device Name: Spectrolyse® PAI-1, Model 101201 Regulation Number: 21 CFR 864.7290 Regulation Name: Factor Deficiency Test Regulatory Class: Class II Product Code: GGP Dated: July 27, 2007 Received: July 30, 2007

Dear Mr. Teiher:

We have reviewed your Section 510(k) premarket notification of intent to market the device wf have to hove 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 Section 510(k) I ins letter witi anow you to begin mailoning of substantial equivalence of your device to a legally prematicate 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), please rr you deen's specific an readiological Health's (CDRH's) Office of Compliance at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to (240) 270 0461. And (21CFR Part 807.97). For questions regarding postmarket surveillance, promance notification - (216-11-15) Surveillance and Biometric's (OSB's) Division of Postmarket product CD111 - For questions regarding the reporting of device adverse events Surveinance at 240 210 3171. For questions of Surveillance Systems at 240-(Medical Dovio Reporting (112 17)) Properal information on your responsibilities under the Act from 270 -401. I ou may of the may of the mational and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Robert Becker

Robert L. Becker, Jr., MD, PhD Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Section 2

STATEMENT OF INDICATIONS FOR USE

Applicant:

510(k) Number: _ KOCO333333

Device:_______________________________________________________________________________________________________________________________________________________________________

Indications for Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Josephine Bautista

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

500(k) K063323

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).