ACTICLOT, MODEL 824

K052124 · American Diagnostica, Inc. · GJS · Oct 17, 2005 · Hematology

Device Facts

• Record ID: K052124
• Device Name: ACTICLOT, MODEL 824
• Applicant: American Diagnostica, Inc.
• Product Code: GJS · Hematology
• Decision Date: Oct 17, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7750
• Device Class: Class 2

Intended Use

The ACTICLOT® dPT™ is intended for the qualitative determination of lupus anticoagulants (LA) in human plasma. This test is for in vitro diagnostic use.

Device Story

ACTICLOT® dPT™ is a reagent kit for qualitative detection of Lupus Anticoagulants (LA) in citrated human plasma. Kit includes dPT™ Activator (recombinant tissue factor), LA Buffer™, and LA Phospholipids™. Operates via two-step clotting assay: screening protocol (plasma + buffer + activator) and confirmatory protocol (plasma + phospholipids + activator). Performed on semi-automated or automated coagulation analyzers in clinical laboratory settings. Prolonged screening clot time indicates potential LA; significant reduction in confirmatory clot time confirms presence. Results assist clinicians in diagnosing LA-related coagulation disorders. Bypasses contact intrinsic pathway, excluding interference from Factor XI/XII deficiencies.

Clinical Evidence

Bench testing and method comparison studies performed. Precision evaluated across four coagulation analyzers (ACL 300R, BCT, MLA 900C, STA Compact) with intra-assay CVs 0.5-3.8% and inter-assay CVs 3.2-8.6%. Method comparison with predicate (n=143 samples across two sites) showed 87.6-90.7% agreement. Clinical sensitivity study (n=23 prescreened LA positive samples) showed 78.3% sensitivity, comparable to predicate (78.3%) and aPTT-based LA tests (82.6%). Interference testing confirmed no impact from heparin up to 1.0 U/mL; potential interference noted for lipemic, icteric, hemolysed samples and oral anticoagulants.

Technological Characteristics

Reagent kit containing recombinant tissue factor (dPT™ Activator), LA Buffer™, and LA Phospholipids™. Clotting assay based on extrinsic coagulation pathway activation. Compatible with semi-automated and automated coagulation analyzers. No specific materials of construction or connectivity standards specified.

Indications for Use

Indicated for the qualitative determination of lupus anticoagulants (LA) in human plasma for in vitro diagnostic use.

Regulatory Classification

Identification

A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).

Predicate Devices

• DVVtest® and DVVconfirm® (K940490)

Submission Summary (Full Text)

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

Image /page/0/Picture/0 description: The image shows a stylized American flag design. The flag's stripes are represented by solid black bars. In the upper left corner, where the stars would typically be, there is the text "ai" with a square and diamond symbol above it. The text and symbols are white, contrasting with the black stripes.

american diagnos

Creating products for life

0CT 17 2005

## 510(k) SUMMARY

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

The assigned 510(k) number is: K052124

## Submitted by:

American Diagnostica Inc. 500 West Avenue Stamford, CT 06902 Tel. [phone] Fax [phone]

## Contact:

Leigh Ayres Director of Regulatory Affairs and Quality Assurance 203-602-7777 x 14 or

Clare Santulli Coagulation Manager and Field Trial Coordinator Phone: [phone] x 25

## Summary Prepared:

July 26, 2005

## Subject Device Information:

Catalogue number: 824

Device Name: Dilute Prothrombin Time

Proprietary/Trade name: ACTICLOT® dPT™

Common Name: LA test

Classification Name: Prothrombin Time Test

Device Classification: Class II

Regulation Number: Title 21 CFR § 864.7750

Panel: Hematology Reagents

Product Code: GJS

500 West Avenue, P.O. Box 110215, Stamford, CT. 06911-0215 Tel. [phone] • Fax. [phone]

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

## Predicate Device Information:

Catalogue numbers: 810 and 815

Device Name: Dilute Russell's Viper Venom Test

Proprietary/Trade name: DVVtest" and DVVconfirm"

Common Name: LA test

Classification Name: Russell Viper Venom Reagent

Device Classification: Class I

Regulation Number: Title 21 CFR § 864.8950

Panel: Hematology Reagents

Product Code: GIR

K Number: K940490

## Description of the Device:

ACTICLOT® dPT" is a test kit. It has three reagents that are used selectively for a screening protocol and a confirmatory protocol. LA Buffer" is used with dPT Activator" for the screening protocol. LA Phospholipids" is used with dPT Activator" for the confirmatory protocol. ACTICLOT® dPT" is a professional use qualitative test.

## Intended Use:

The ACTICLOT* dPT" is intended for the qualitative determination of lupus anticoagulants (LA) in human plasma. This test is for in vitro diagnostic use.

## Summary of Substantial Equivalence:

ACTICLOT® dPT™ is substantially equivalent to the predicate device DVV(est" and DVVconfirm® (manufactured by American Diagnostica Inc.. Stamford. CT) in performance and intended use. This statement is based on the following criteria: intended use, methodology and test principle, operating procedures, sample requirements, reconstituted stability, specimen, precision, and accuracy from method comparison studies. The summary of substantial equivalence is shown on TABLE 1.

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

# TABLE 1: Summary of Substantial Equivalence for ACTICLOT® dPT" and DVViest® and DVVconfirm®

| | ACTICLOT® dPT™ | DVVtest® and DVVconfirm® |
|--------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ACTICLOT® dPT™ is intended<br>for the qualitative determination of<br>lupus anticoagulants (LA) in human<br>plasma. This test is for <i>in vitro</i><br>diagnostic use | The DVVtest® and DVVconfirm® are<br>intended for the qualitative<br>determination of lupus anticoagulants<br>(LA) in human plasma. This test is for<br><i>in vitro</i> diagnostic use. |
| Methodology<br>and Test<br>Principle | The dPT Activator™ reagent contains<br>lipidated tissue factor and calcium.<br>When it is mixed with LA Buffer™ in<br>the screening protocol, it is used to<br>initiate clotting in plasma and then<br>instrumentation is used to measure the<br>clot time. In the confirmatory<br>protocol, the dPT Activator™ and LA<br>Phospholipids™ reagent is added to<br>plasma and instrumentation is used to<br>determine clot time. | The reagent, Russell's Viper Venom,<br>in DVVtest® is used to initiate clotting<br>in plasma and then instrumentation is<br>used to measure the clot time. The<br>Russell's Viper Venom and<br>phospholipids in DVVconfirm® is used<br>to initiate clotting in plasma and then<br>instrumentation is used to measure<br>clot time. |
| Operating<br>Procedures | Lyophilized reagents are reconstituted<br>prior to use and then aliquots of<br>reagents and plasma are combined and<br>then analyzed. There are no<br>calibrators. The kit contains reagents<br>and instructions for a screening<br>protocol, a confirmatory protocol, and<br>mixing studies. | The lyophilized reagents are<br>reconstituted prior to use and then<br>aliquots of reagents and plasma are<br>combined and then analyzed. There<br>are no calibrators. DVVtest® reagent<br>is used for the screening test.<br>DVVconfirm® reagent is used for the<br>confirmatory test. These two kits<br>contain protocols for mixing studies. |
| Sample<br>Requirements | Blood is drawn with blood collection<br>tubes containing trisodium citrate and<br>then the tubes are centrifuged. Plasma<br>is collected from the tubes and then it<br>is tested. | Blood is drawn with blood collection<br>tubes containing trisodium citrate and<br>then the tubes are centrifuged. Plasma<br>is collected from the tubes and then it<br>is tested. |
| Reconstituted<br>Stability | dPT Activator™ is stable for 24 hours<br>at 18° - 25°C.<br>LA Buffer™ and LA Phospholipids™<br>are stable for 10 days at 2° - 8°C or at<br>18° -25°C. | DVVtest® and DVVconfirm® are stable<br>for 24 hours at 18° -25°C or 5 days at<br>2°-8°C or 1 month at -20°C. |
| Specimen | Citrated platelet poor plasma | Citrated platelet poor plasma |
| Precision | Equivalent (See TABLE 2) | Equivalent (See TABLE 3) |
| Method<br>Comparison<br>(accuracy) | Equivalent (See TABLES 4 and 5) | Equivalent (See TABLES 4 and 5) |

500 West Avenue, P.O. Box 110215, Stamford, CT. 06911-0215 Tel. [phone] • Fax. [phone] Page 3 of 7

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

## Precision

ACTICLOT® dPT" and DVVtest" reagent and the DVVconfirm® reagent precision studies were performed by American Diagnostica Inc. and one ficld trial laboratory using various coagulation analyzers: ACL® 300R centrifugal analyzer, BCT*, MLA* 900C coagulation analyzer, and the STA Compact". LAtrol" Abnormal Control (catalogue number 816A) and LAtrol" Normal Control (catalogue number 816N) were the controls that were tested for the precision evaluation. These precision studies included multiple tests performed over several days. The precision results from the subject device are shown in TABLE 2.

| Coagulation<br>Analyzer | Control | dPT<br>Screening<br>mean<br>(sec) | Intra-<br>Assay<br>CV (%) | Inter-<br>Assay<br>CV (%) | dPT<br>Confirm-<br>atory<br>mean<br>(sec) | Intra-<br>Assay<br>CV (%) | Inter-<br>Assay<br>CV (%) |
|-------------------------|---------|-----------------------------------|---------------------------|---------------------------|-------------------------------------------|---------------------------|---------------------------|
| ACL ® 300R | 816N | 32.8 | 2.5 | 5.1 | 30.2 | 3.8 | 5.3 |
| | 816A | 63.8 | 1.9 | 7.1 | 36.9 | 3.2 | 3.8 |
| BCT® | 816N | 47.5 | 0.5 | 3.2 | 51.6 | 1.7 | 4.5 |
| | 816A | 89.2 | 0.6 | 5.2 | 61.9 | 1.2 | 3.7 |
| MLA® 900C | 816N | 27.9 | 2.5 | 3.7 | 27.2 | 2.8 | 4.1 |
| | 816A | 51.6 | 2.4 | 8.6 | 30.5 | 1.5 | 3.7 |
| STA<br>Compact® | 816N | 40.2 | 0.8 | 3.4 | 39.7 | 0.9 | 4.3 |
| | 816A | 77.9 | 1.1 | 7.2 | 46.0 | 1.0 | 4.8 |

| | | | TABLE 2. Precision Study Results with ACTICLOT* dPT™ | | |
|--|--|--|------------------------------------------------------|--|--|
|--|--|--|------------------------------------------------------|--|--|

ND -- Not Determined

The results of precision study performed with the predicate device are shown in TABLE 3.

| Coagulation<br>Analyzer | Control | DVVtest<br>(sec)<br>mean | Intra-<br>Assay<br>CV (%) | Inter-<br>Assay<br>CV (%) | DVV<br>confirm<br>(sec)<br>mean | Intra-<br>Assay<br>CV (%) | Inter-<br>Assay<br>CV (%) |
|-------------------------|---------|--------------------------|---------------------------|---------------------------|---------------------------------|---------------------------|---------------------------|
| ACLR 300R | 816N | 30.4 | 1.4 | ND | 31.3 | 0.6 | ND |
| | 816A | 64.2 | 3.2 | ND | 35.1 | 1.4 | ND |
| BCTR | 816N | 31.8 | 0.3 | 2.4 | 33.2 | 0.5 | 3.7 |
| | 816A | 63.8 | 0.5 | 2.7 | 43.0 | 0.6 | 4.8 |
| MLAR 900C | 816N | 31.0 | 0.9 | 2.9 | 31.7 | 1.3 | 2.3 |
| | 816A | 63.6 | 1.4 | 3.9 | 34.5 | 0.9 | 3.2 |
| STA<br>CompactR | 816N | 36.2 | 0.7 | 3.3 | 34.4 | 0.7 | 3.6 |
| | 816A | 71.9 | 0.9 | 3.8 | 38.9 | 1.3 | 5.6 |

TABLE 3. Precision Study Results with DVVtest® and DVVconfirm*

Not Determined ND

500 West Avenue, P.O. Box 110215, Stamford, CT. 06911-0215 Tel. [phone] • Fax. [phone] Page 4 of 7

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

## Conclusion concerning the Precision Study:

Precision data obtained from laboratory field tests and from testing at American Diagnostica Inc. show that ACTICLOT" dPT" and DVVest and DVV confirm are substantially equivalent. The precision data obtained from each instrument is substantially equivalent because the intra-assay CVs were within 3.8% and the inter-assay CVs were within 7.2%. The mean clotting times from the precision studies are shown for informational purposes only. Clotting times of the two comparative methods are not expected to be the same because both the predicate method and subject method have systematic bias''' based upon differences in mechanism of initiation of clot formation and instrument system bias in assessing clot time of each method.

## Method Comparison (accuracy)

ACTICLOT* method comparison studies were performed at American Diagnostica, Inc. in Stamford, CT (Study 1) and at Centre hospitalier universitaire de Sherbrooke, Fleurimont (Québec), Canada (Study 2). Patient samples were tested using ACTICLOT® dPT" and DVVtesst" and DVVconfirm®. The accuracy matrix of each study is displayed on TABLE 4 and TABLE 5.

## TABLE 4. Accuracy Matrix of Study 1

| | Number of samples that were<br>LA positive with DVVtest R<br>and DVVconfirmR | Number of samples that were<br>LA negative with DVVtestR and<br>DVVconfirmR |
|--------------------------------------------------------------------|------------------------------------------------------------------------------|-----------------------------------------------------------------------------|
| Number of samples that<br>were LA positive with<br>ACTICLOTR dPTTM | 17 | 5 |
| Number of samples that<br>were LA negative with<br>ACTICLOTR dPTTM | 0 | 32 |

## TABLE 5. Accuracy Matrix of Study 2

| | Number of samples that were<br>LA positive with DVV <i>test</i> ®<br>and DVV <i>confirm</i> ® | Number of samples that were<br>LA negative with DVV <i>test</i> ® and<br>DVV <i>confirm</i> ® |
|-------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|
| Number of samples that<br>were LA positive with<br>ACTICLOT® dPT™ | 31 | 8 |
| Number of samples that<br>were LA negative with<br>ACTICLOT® dPT™ | 3 | 50 |

500 West Avenue, P.O. Box 110215, Stamford, CT. 06911-0215 Tel. [phone] • Fax. [phone] Page 5 of 7

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

## Conclusion Concerning the Method Comparison Studies:

The accuracy studies from the laboratory field test and from testing at American Diagnostica Inc. show that ACTICLOT * dPT" and DVV confirm are substantially equivalent. In Study 1, 49 out of 54 samples tested (90.7%) were in agreement. In Study 2, 81 out of 93 samples tested (87.1%) were in agreement. The accuracy or agreement of these two methods was between 87.1% and 90.7%.

## Sensitivity Studies:

Twenty-three prescreened LA positive samples were tested at the Haemotology Department at Univeristy College London. UK with the predicate device, and a third commercially available aPTT schsitive I.A test (Dade" Actin' FSL Activated PTT Reagent). The test results are shown on TABLE 6.

| | ACTICLOT® dPT™ a | DVVtest®/DVVconfirm® b | aPTT reagentb |
|--------------------------------------------------------------------------------------------------------|------------------|------------------------|---------------|
| Number of Samples<br>that Tested LA<br>Positive with One<br>LA Test / Number of<br>LA Positive Plasmas | 18/23 | 18/23 | 19/23 |
| Percent LA Positive | 78.3% | 78.3% | 82.6% |

TABLE 6. Percent LA Positive Test Results from each of Three LA Tests

(a) Assays were performed using the ACL. 300R coagulation analyzer.

(b) Assays were performed using the Sysmex CA-1500 coagulation analyzer.

## Conclusion Concerning Sensitivity:

The London study shows that the sensitivity of ACTICLOT* dPT" and DVV1est" and DVVconfirm are substantially equivalent because the subject method identified and the predicate method identified 18 of the 23 LA positive samples. The third method was included for informational purposes.

It is well known, in the haemostasis field, that no one LA test identifies all LA positive samples due to the biochemical heterogencity among lupus anticoagulants and the heterogeneity among LA test reagents 2. It is recommended that LA positive samples should be identified after testing with a combination of two or more LA tests 33. When the test results from these three methods were combined, 21 of the 23 LA positive samples were identified. The results from the combined tests are shown in TABLE 7. This increased the percent LA positive from 78.3% - 82.6% (with individual tests) to 91.3% when test results were combined.

{6}------------------------------------------------

#### Percent LA Positive Test Results with Two or More LA Positive Tests from Three TABLE 7. LA Tests

| | Samples tested with<br>ACTICLOT® dPT™a + DVVtest®/DVVconfirm®b + aPTT reagentb |
|--------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------|
| Number of Samples<br>that Tested LA<br>Positive with any<br>Two out of Three<br>LA Tests / Number<br>of Known LA<br>Positive Samples | 21/23 |
| Percent LA Positive | 91.3 % |

(a) Assays were performed using the ACL 300R coagulation analyzer.

(b) Assays were performed using the Sysmex CA-1500 coagulation analyzer.

#### REFERENCES

- Tietz, NW. Textbook of Clinical Chemistry. Saunders. 1986: 412-413. l.
- Brandt, JT, Triplett, DA, Alving, IS, Scharrer, I. Criteria for the Diagnosis of Lupus Anticoagulants: an 2. Update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardization Committee of the ISTH. Thromb Haemost. 1995: 74(4):1185-90.
- Johns, AS, Chamley, L, Ocklford, PA, Pattison, NS, Mckay, EJ, Corkill, M. Hart, H. Comparison of 3. Tests for the Lupus Anticoagulant and Antiphopholipid Antibodies in Systemic Lupus Erythematosus. Clin Exper Rheumatol. 1994: 12: 523-6.

{7}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. In the center of the circle is an abstract image of what appears to be an eagle.

# OCT 17 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Leigh Ayres Director of Regulatory Affairs and Quality Assurance American Diagnostica, Inc. 500 West Avenue Stamford, Connecticut 06902

Re: k052124 Trade/Device Name: ACTICLOT® dPT™ Reagent Kit Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin time test Regulatory Class: II Product Code: GJS Dated: August 3, 2005 Received: August 5, 2005

Dear Ms. Ayres:

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 requirc 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 adultcration.

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Scction 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.

{8}------------------------------------------------

Page 2 -

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 [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert L. Becker Jr.

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

Enclosure

{9}------------------------------------------------

# INDICATIONS FOR USE STATEMENT

K052134 510(k) Number:

Device name: ACTICLOT® dPT™ reagent kit

## Indications for Use:

The ACTICLOT® dPT™ is intended for the qualitative determination of Lupus Anticoagulants (LA) in human plasma. The test is for in vitro diagnostic use.

Concurrence of CDRH, Office of Device Evaluation (ODE)

Image /page/9/Picture/6 description: The image shows a square with an X drawn inside it. The X is formed by two diagonal lines that intersect in the center of the square. The lines extend from corner to corner, creating a clear and simple visual representation of a cross mark within a square boundary.

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter-Use

Josephine Bautista

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K052124