The Phosphoplastin RL Prothrombin Time reagent is a liquid PT reagent containing thromboplastin derived from rabbit brain and calcium ions for use in the determination of Prothrombin Time (PT) and related coagulation procedures. The PT test is a one-stage test used in routine patient screening for disorders in the extrinsic pathway of coagulation and for monitoring patients undergoing Oral Anti-Coagulant (OAC) therapy. Phosphoplastin RL should only be used in an appropriate clinical laboratory by qualified laboratory personnel and is provided ready-to-use.

Device Description

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study information for the R2 Diagnostics Phosphoplastin RL device:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Phosphoplastin RL device are not explicitly stated in a dedicated section with specific numerical thresholds. Instead, the document compares its performance to a predicate device (Phosphoplastin R) to demonstrate substantial equivalence. The implied acceptance criteria revolve around achieving similar performance characteristics.

Performance Metric	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (Phosphoplastin RL)
Correlation with Predicate (INR data)	High correlation (e.g., r² approaching 1) and reasonable slope to the predicate device.	Site 1 (Photo-optical): r² = 0.986, slope = 0.882Site 2 (Mechanical): r² = 0.915, slope = 1.162
Within-run Precision (CV)	CVs less than 3% (based on predicate device's reported performance in manufacturer's insert).	CVs less than 3%
Between-run Precision (CV)	CVs less than 3% (based on predicate device's reported performance in manufacturer's insert).	CVs less than 3%
Sensitivity	Ability to detect deficiencies in factors II, V, VII, and X (PT and PT-based factor assays) and sensitivity to oral anticoagulants.	Formulated to detect deficiencies in factors II, V, VII, and X (PT and PT-based factor assays). Sensitive to oral anticoagulants. (Stated as similar to predicate)

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

Sample Size: The document states that "normal and abnormal patient plasma, as well as plasma samples from patients undergoing oral anticoagulant therapy, were tested." However, the specific number of samples for the test set is not provided.
Data Provenance: The correlation studies were conducted at "two sites." The information does not specify the country of origin, but given the applicant's address (South Bend, IN, USA) and the FDA submission, it's highly likely the studies were conducted in the USA. The studies appear to be retrospective in nature, using existing plasma samples.

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

There is no mention of experts being used to establish a ground truth for the test set. The study compares the performance of the new device against an existing, legally marketed predicate device (Phosphoplastin R), which itself would have established its own reference values during its development. For in-vitro diagnostics like this, the "ground truth" is typically the result obtained from the predicate device or a recognized reference method.

4. Adjudication Method for the Test Set

There is no mention of an adjudication method. As noted above, the study is a comparison against a predicate device, rather than an assessment needing expert interpretation of novel data to establish ground truth.

5. If a Multi-reader Multi-case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-reader Multi-case (MRMC) comparative effectiveness study was not done. This type of study is more common for imaging or diagnostic devices where human readers interpret results, and the AI's role is to assist or replace that interpretation. This device is an in-vitro diagnostic reagent, where the output is typically a numerical value (PT/INR), rather than an image or complex data requiring reader interpretation.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

This is an in-vitro diagnostic reagent, not an algorithm in the typical sense of AI/ML. The "device" itself is the reagent. The performance described is inherently "standalone" in that it's the reagent's performance in generating a PT/INR value when exposed to plasma, independent of human interpretive intervention after the test is run. However, the test is performed in a clinical laboratory by “qualified laboratory personnel,” meaning it's always used with human involvement in its application and result interpretation within a broader clinical context.

7. The Type of Ground Truth Used

The "ground truth" here is the results obtained from the legally marketed predicate device, Phosphoplastin R. The new device's performance is validated by its ability to produce results that are highly correlated and similar to those produced by the predicate device on the same plasma samples.

8. The Sample Size for the Training Set

There is no mention of a training set sample size. This type of device is a chemical reagent, not an AI/ML algorithm that requires a training set. Its formulation is based on biochemical principles, not data-driven learning.

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

As there is no training set for this type of device, this question is not applicable.

Summary

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8.0 Premarket Notification 510(k) Summary[As required by section 807.92(c)]
Applicant:	Michael J. MorrisR2 Diagnostics, Inc.412 South Lafayette Blvd.South Bend, IN 46601USA
Contact:	Dr. Peggy S. CarterR2 Diagnostics, Inc.412 South Lafayette Blvd.South Bend, IN 46601TEL: (574) 288-4377FAX: (574) 288-2272
Date:	December 19, 2003
Trade Name:	R2 Diagnostics Phosphoplastin RI
Common Name:	Prothrombin Time
Classification Name:	Test, Time, Prothrombin(per 21 CFR section 864.7750)
Comparison Device:	Phosphoplastin R, K940082

Description of the Device and Intended Use

Phosphoplastin RL PT reagent is a liquid, ready-to-use reagent containing thromboplastin derived from rabbit brain, calcium ions, buffers, stabilizers and preservatives. Phosphoplastin RL is intended for use in a one-stage prothrombin time (PT) test on citrated human plasma. The PT test is a quantitative assay used in the general patient population for routine screening to detect deficiencies in the extrinsic pathway of coagulation. The PT test is also used to monitor oral anticoagulant therapy and should be used in a clinical laboratory by qualified laboratory personnel.

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Summary of Substantial Equivalence Comparisons

R2 Diagnostics Phosphoplastin RL is substantially equivalent in intended use and performance to Phosphoplastin R. Both the predicate device and the proposed product are formulated to detect deficiencies in factors II, V, VII, and X (PT and PT-based factor assays). Both reagents are also sensitive to oral anticoagulants. In correlation studies normal and abnormal patient plasma, as well as plasma samples from patients undergoing oral anticoagulant therapy, were tested using both reagents. Comparison of INR data from PT testing at two sites and on two different instrument types yielded correlation coefficients of r2 = 0.986 (photo-optical), slope = 0.882 and r2 = 0.915 (mechanical), slope = 1.162. Within-run and between-run precision studies were also performed and CV's of less than 3% were obtained for the proposed device. CV's of less than 3% are also reported for the predicate device in the manufacturers directional insert.

Conclusion: Substantial Equivalence Statement

In Summary, the identical intended use, similar technological characteristics and the performance data provided in this premarket notification demonstrate that R2 Phosphoplastin RL is substantially equivalent to Phosphoplastin R.

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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 eagle with three stripes forming its body and wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Peggy Carter, Ph.D. Director, Product Development R2 Diagnostics 412 S. Lafayette Boulevard South Bend, Indiana 46601

MAY 2 4 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Re: K040296

Trade/Device Name: Phosphoplastin RL Regulation Number: 21 CFR § 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: II Product Code: GJS Dated: May 4, 2004 Received: May 5, 2004

Dear Dr. Carter:

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 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.

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If you desire specific information about the application of labeling requirements to your device, or guestions 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,

Joseph L. Arblett

Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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6.0 Indications for Use

510(k) Number (if known)K040296

Phosphoplastin RL Device Name:

Indications for Use:

Statement of Indications for Use

The Phosphoplastin RL Prothrombin Time reagent is a liquid PT reagent containing 1 no 1 hoophopiastin derived from rabbit brain and calcium ions for use in the determination of Prothrombin Time (PT) and related coagulation procedures. The PT test is a one-stage I roubomom This (1 ) (1 ) (1 ) (1 ) ) ) (1 ) ) = (1 ) = ) = (1 ) = ) = (1 ) = (1 ) = ) = (1 ) test is used in routine patient screening for disorders in the extrinsic pathway of test is used in round panel patients undergoing Oral Anti-Coagulant (OAC) therapy. Phosphoplastin RL should only be used in an appropriate clinical laboratory by qualified laboratory personnel and is provided ready-to-use.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Josephine Runtadi
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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510(k) K040296

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
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).(b)
Classification. Class II (performance standards).