STA- NeoPTimal

K211485 · Diagnostica Stago S.A.S · GJS · Dec 23, 2022 · Hematology

Device Facts

• Record ID: K211485
• Device Name: STA- NeoPTimal
• Applicant: Diagnostica Stago S.A.S
• Product Code: GJS · Hematology
• Decision Date: Dec 23, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7750
• Device Class: Class 2

Intended Use

The STA- NeoPTimal kits provide thromboplastin reagents from rabbit brain extract, for the quantitative determination, in human citrated plasma (3.2% sodium citrate), of Prothrombin Time (PT) on STA-R family, STA Compact family and STA Satellite family instruments. STA- NeoPTimal is a coagulation screening test intended to be used by professional laboratory personnel for the evaluation of the extrinsic coagulation pathway and the monitoring of oral vitamin K antagonist therapy using the International Normalized Ratio (INR).

Device Story

STA-NeoPTimal is an in-vitro diagnostic kit containing lyophilized rabbit brain thromboplastin and a calcium-containing solvent. It is used on Stago coagulation analyzers (STA-R, STA Compact, and STA Satellite families) to measure Prothrombin Time (PT). The device functions by triggering the extrinsic coagulation pathway; the instrument measures the time required for a fibrin clot to form. The reagent includes a specific heparin inhibitor to ensure PT prolongation reflects deficiencies in factors II, V, VII, X, or fibrinogen. Results are expressed in seconds or as an International Normalized Ratio (INR). The device is intended for use by professional laboratory personnel in clinical settings to monitor patients on vitamin K antagonist therapy. By providing standardized PT/INR measurements, the device assists clinicians in adjusting anticoagulant dosages, thereby helping to manage patient coagulation status and reduce risks associated with therapy.

Clinical Evidence

Bench testing only. Precision/reproducibility studies were conducted over 20 days at external sites using 11 samples across the measuring range. Method comparison study against the predicate device (Thromborel S) across four sites showed a Pearson correlation of 0.965, with a slope of 0.93 and intercept of 0.04. Reference interval established using 137 patients (11.8–14.9 seconds; 0.89–1.11 INR).

Technological Characteristics

Lyophilized rabbit brain thromboplastin reagent with specific heparin inhibitor and calcium solvent. Dimensions/form factor: 5mL and 10mL vials. Connectivity: Integrated with STA-R, STA Compact, and STA Satellite instrument families. Sterility: Not applicable (no direct patient contact).

Indications for Use

Indicated for professional laboratory use in human patients for the evaluation of the extrinsic coagulation pathway and monitoring of oral vitamin K antagonist therapy via Prothrombin Time (PT) and International Normalized Ratio (INR).

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

• Thromborel S (K003870)

Submission Summary (Full Text)

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December 23, 2022

Diagnostica Stago SAS % Anthony Dennis US Market Access Director Diagnostica Stago Inc. 5 Century Drive Parsippany, New Jersey 07054

Re: K211485

Trade/Device Name: STA - NeoPTimal Regulation Number: 21 CFR 864.7750 Regulation Name: Prothrombin Time Test Regulatory Class: Class II Product Code: GJS Dated: September 2, 2022 Received: September 6, 2022

Dear Anthony Dennis:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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

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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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Image /page/1/Picture/5 description: The image shows the text "Min Wu-S" in a large, bold, sans-serif font. The text is black against a white background. The words are spaced apart, with a hyphen connecting "Wu" and "S". The text appears to be a name or title.

Min Wu Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known)

K211485

Device Name STA - NeoPTimal

#### Indications for Use (Describe)

The STA- NeoPTimal kits provide thromboplastin reagents from rabbit brain extract, for the quantitative determination, in human citrated plasma (3.2% sodium citrate), of Prothrombin Time (PT) on STA-R family, STA Compact family and STA Satellite family instruments. STA- NeoPTimal is a coagulation screening test intended to be used by professional laboratory personnel for the evaluation of the extrinsic coagulation pathway and the monitoring of oral vitamin K antagonist therapy using the International Normalized Ratio (INR).

| Type of Use (Select one or both, as applicable) | |
|------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|
| <span style="text-decoration: overline;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="text-decoration: overline;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) |

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Image /page/3/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in a red, serif font. Above the word "Stago" are two abstract shapes. The shape on the left is red, and the shape on the right is brown.

#### ട്. 510(k) SUMMARY

| General Information | | | | | | |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|
| Submitter Information: | Diagnostica Stago, Inc.<br>5 Century Drive<br>Parsippany, NJ 07054<br>Primary Contact: Anthony Dennis, MBA, RAC, CBA (ASQ)<br>Director, US Market Access<br>Phone: 1 – (973) – 775-1200 x4162<br><br>On Behalf of: Diagnostica Stago SAS | | | | | |
| Date of Submission: | 12 May 2021; Revised 22 October 2022 | | | | | |
| Device Information | | | | | | |
| Device Trade Name: | STA® - NeoPTimal | | | | | |
| Regulatory Information | | | | | | |
| Classification Name: | Test Time Prothrombin | | | | | |

#### Classification Name: Test, Time, Prothrombin Regulatory Class: Class II Panel: Hematology Product Code: Gla Regulation Number 21 CFR 864.7750 Predicate Device: Thromborel® S (K003870)

## Device Intended Use

The STA®- NeoPTimal kits provide thromboplastin reagents from rabbit brain extract, for the quantitative determination, in human citrated plasma (3.2% sodium citrate), of Prothrombin Time (PT) on STA-R® family, STA Compact® family and STA Satellite® family instruments. STA®- NeoPTimal is a coagulation screening test intended to be used by professional laboratory personnel for the evaluation of the extrinsic coagulation pathway and the monitoring of oral vitamin K antagonist therapy using the International Normalized Ratio (INR).

#### Device Description

The in-vitro diagnostic STA® - NeoPTimal kits are available in two sizes and contains:

| Table 1 - Description of STA® – NeoPTimal Kits | |
|------------------------------------------------|-------------------------------|
| STA® - NeoPTimal 5 | STA® - NeoPTimal 10 |
| 6 x 5 ml vials of Reagent 1 | 12 x 10 ml vials of Reagent 1 |
| 6 x 5 ml vials of Reagent 2 | 12 x 10 ml vials of Reagent 2 |

Reagent 1 is STA® - NeoPTimal, lyophilized thromboplastin prepared from rabbit brain extract. The STA® - NeoPTimal reagent contains a specific heparin inhibitor. Any prolongation of the prothrombin time is, therefore, related to a real deficiency of factor II, V, VII, X and/or fibrinogen.

Reagent 2 is a solvent containing calcium.

The test consists of the use of calcium thromboplastin to measure the clotting time of the patient's plasma and to compare it with that of a normal standard. The test measures, as a whole, the activities of the coagulation factor II (prothrombin), factor V (proaccelerin), factor VII (proconvertin), factor X (Stuart factor) and factor I (fibrinogen).

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Image /page/4/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be three curved shapes, one red and two brown, arranged in a circular fashion.

The PT value is expressed in seconds or INR. The result has to be interpreted according to the patient's clinical and biological states. The INR value corresponds to the ratio of the patient's PT to that of the standard PT raised to the ISI (International Sensitivity Index) power of the thromboplastin used:

INR = ( Patient's PT / Mean Normal PT ) * ISI

The ISI value of a given thromboplastin is determined by testing normal plasma and VKA (vitamin K antagonist)-treated patient plasma with that thromboplastin and with the International Reference preparation (RBT) for thromboplastin.

| Attributes or<br>characteristics | Dade Behring, Thromborel® S<br>(Predicate device (K003870)) | Diagnostica Stago, STA® - NeoPTimal<br>(Subject device) |
|------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for use | Thromborel S Reagent is used for the<br>determination of the Prothrombin Time (PT)<br>according to Quick and, in conjunction with<br>the relevant deficient plasmas, for the<br>determination of the coagulation factor II,<br>V, VII and X. | The STA®- NeoPTimal kits provide<br>thromboplastin reagents from rabbit brain<br>extract, for the quantitative determination, in<br>human citrated plasma (3.2% sodium<br>citrate), of Prothrombin Time (PT) on STA-<br>R® Family, STA Compact® Family and<br>STA Satellite® Family. STA®- NeoPTimal<br>is a coagulation screening test intended to be<br>used by professional laboratory personnel<br>for the evaluation of the extrinsic<br>coagulation pathway and the monitoring of<br>oral vitamin K antagonist therapy using the<br>International Normalized Ratio (INR). |
| Contents of the Kit | Reagent 1: Lyophilized thromboplastin<br>extracted from human placenta<br>Reagent 2: solvent with calcium<br>Packaging sizes: | Reagent 1: Lyophilized thromboplastin<br>extracted from rabbit brain<br>Reagent 2: solvent with calcium<br>Packaging sizes: |
| | 4 mL<br>10 mL | 5 mL<br>10 mL |
| Assay Method | Clotting Time | Same |
| Test Principle | The Thromborel® S test is a coagulation<br>process triggered by incubation of plasma<br>with the optimal amount of thromboplastin<br>and calcium. The time to formation of a<br>fibrin clot is then measured. | The STA® - NeoPTimal test consists of the<br>use of calcium thromboplastin to measure<br>the clotting time of the patient's plasma and<br>to compare it with that of a normal standard.<br>The test measures, as a whole, the activity o<br>the coagulation factor II (prothrombin),<br>factor V (proaccelerin), factor VII<br>(proconvertin), factor X (Stuart factor) and<br>factor I (fibrinogen). |
| Anatomical Sites | Not applicable. No direct patient contact. | Same |
| Where Used: hospital,<br>home, ambulance, etc. | Hospital Laboratory or other Health Care<br>Laboratory. | Same |
| Sterility | No sterility requirements. No direct patient<br>contact | Same |
| Biocompatibility | No biocompatibility requirements. No direct<br>patient contact. | Same |
| Attributes or<br>characteristics | Dade Behring, Thromborel® S<br>(Predicate device (K003870)) | Diagnostica Stago, STA® - NeoPTimal<br>(Subject device) |
| Chemical Safety | No issues regarding chemical safety due to<br>no direct patient contact | Same |
| Analyzers | Sysmex® CA series and Siemens BCS<br>series | STA-R® Family, STA Compact® Family<br>and STA Satellite® Family |

# Substantial Equivalence

Table 2 – Comparison of the STA® - NeoPTimal to the Predicate Device

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Image /page/5/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be two curved shapes, one red and one brown, arranged in a way that suggests movement or flow. The overall design is simple and modern.

STA® - NeoPTimal is substantially equivalent to the predicate device, Thromborel® S (K003870) in indication/intended use, test principle, assay method and performance; thus yielding no new questions in safety and effectiveness.

#### Standards/Guidance Documents Referenced:

- CLSI EP25-A - Evaluation of Stability of In Vitro Diagnostic Reagents. Approved Guideline
- . CLSI EP09c, Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline
- CLSI H47-A2, One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time . (APTT) Test, 2nd Edition
- . CLSI EP5-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline -Third Edition.
- . CLSI H48-2ed, Determination of Coagulation Factor Activities Using the One-Stage Clotting Assay -Second Edition
- EP07-A2 Interference Testing in Clinical Chemistry; Approved Guideline
- CLSI H54-A Procedures for Validation of INR and Local Calibration of PT/INR Systems; Approved Guideline
- . EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - 3rd Edition

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Image /page/6/Picture/0 description: The image contains the word "Stago" in a red, serif font. Above the word, there is a stylized logo consisting of two curved shapes. The top shape is red, and the bottom shape is brown, creating a sense of movement or flow.

# Performance Characteristics

#### Precision/Reproducibility

Single-site precision testing was performed over 20 days at one external site on the STA Compact Max, and STA Satellite. 11 samples were tested across the measuring range, with two replicates per day. Each run was at least two hours apart. The acceptance criteria were met for all samples in the studies.

| | STA R Max - All lots (seconds) | | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | |
|--------|--------------------------------|--------|--|---------------|------|-------------|------|-------------|------|------------|------|-------------|------|-------|------|
| Sample | N | Mean | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 14.270 | | 0.119 | 0.83 | 0.140 | 0.98 | 0.081 | 0.57 | 0.201 | 1.41 | 0.000 | 0.00 | 0.201 | 1.41 |
| 2 | 240 | 13.861 | | 0.126 | 0.91 | 0.132 | 0.95 | 0.104 | 0.75 | 0.210 | 1.52 | 0.000 | 0.00 | 0.210 | 1.52 |
| 3 | 240 | 30.888 | | 0.341 | 1.10 | 0.700 | 2.27 | 0.309 | 1.00 | 0.838 | 2.71 | 0.248 | 0.80 | 0.874 | 2.83 |
| 4 | 240 | 45.502 | | 0.416 | 0.91 | 0.951 | 2.09 | 0.000 | 0.00 | 1.038 | 2.28 | 0.364 | 0.80 | 1.100 | 2.42 |
| 5 | 240 | 62.892 | | 0.527 | 0.84 | 1.413 | 2.25 | 0.517 | 0.82 | 1.594 | 2.53 | 0.471 | 0.75 | 1.662 | 2.64 |
| 6 | 240 | 70.665 | | 0.783 | 1.11 | 2.062 | 2.92 | 0.000 | 0.00 | 2.206 | 3.12 | 0.456 | 0.65 | 2.253 | 3.19 |
| 7 | 240 | 26.270 | | 0.339 | 1.29 | 0.520 | 1.98 | 0.000 | 0.00 | 0.621 | 2.36 | 0.190 | 0.72 | 0.649 | 2.47 |
| 8 | 240 | 14.831 | | 0.138 | 0.93 | 0.138 | 0.93 | 0.052 | 0.35 | 0.202 | 1.36 | 0.028 | 0.19 | 0.204 | 1.38 |
| 9 | 240 | 26.111 | | 0.256 | 0.98 | 0.656 | 2.51 | 0.108 | 0.41 | 0.712 | 2.73 | 0.000 | 0.00 | 0.712 | 2.73 |
| 10 | 240 | 14.908 | | 0.125 | 0.84 | 0.184 | 1.23 | 0.000 | 0.00 | 0.222 | 1.49 | 0.000 | 0.00 | 0.223 | 1.50 |
| 11 | 240 | 38.953 | | 0.307 | 0.79 | 1.056 | 2.71 | 0.000 | 0.00 | 1.100 | 2.82 | 0.000 | 0.00 | 1.100 | 2.82 |

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Image /page/7/Picture/0 description: The image contains the word "Stago" in a red, serif font. Above the word is a logo consisting of two abstract shapes. The top shape is red and resembles a curved leaf or petal, while the bottom shape is brown and appears to be a drop or tear shape. The logo is positioned directly above the text, creating a visual association between the shapes and the company name.

| STA R Max - All lots (INR) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | | |
|----------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 1.0422 | 0.010 | 0.96 | 0.010 | 0.96 | 0.006 | 0.58 | 0.015 | 1.47 | 0.014 | 1.34 | 0.021 | 2.01 |
| 2 | 240 | 1.0120 | 0.009 | 0.89 | 0.010 | 0.99 | 0.007 | 0.69 | 0.015 | 1.50 | 0.015 | 1.48 | 0.021 | 2.08 |
| 3 | 240 | 2.3171 | 0.027 | 1.17 | 0.054 | 2.33 | 0.023 | 0.99 | 0.065 | 2.79 | 0.050 | 2.16 | 0.082 | 3.54 |
| 4 | 240 | 3.4577 | 0.032 | 0.93 | 0.075 | 2.17 | 0.000 | 0.00 | 0.082 | 2.36 | 0.095 | 2.75 | 0.125 | 3.62 |
| 5 | 240 | 4.8318 | 0.042 | 0.87 | 0.114 | 2.36 | 0.040 | 0.83 | 0.128 | 2.65 | 0.151 | 3.13 | 0.198 | 4.10 |
| 6 | 240 | 5.4507 | 0.062 | 1.14 | 0.164 | 3.01 | 0.000 | 0.00 | 0.175 | 3.22 | 0.170 | 3.12 | 0.244 | 4.48 |
| 10 | 240 | 1.0913 | 0.010 | 0.92 | 0.014 | 1.28 | 0.000 | 0.00 | 0.017 | 1.58 | 0.016 | 1.47 | 0.024 | 2.20 |

| STA Compact Max - All lots<br>(seconds) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | | |
|-----------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 14.401 | 0.191 | 1.33 | 0.159 | 1.10 | 0.075 | 0.52 | 0.260 | 1.80 | 0.000 | 0.00 | 0.259 | 1.80 |
| 2 | 240 | 14.132 | 0.209 | 1.48 | 0.246 | 1.74 | 0.142 | 1.00 | 0.353 | 2.50 | 0.000 | 0.00 | 0.353 | 2.50 |
| 3 | 240 | 29.531 | 0.589 | 1.99 | 1.053 | 3.57 | 0.000 | 0.00 | 1.207 | 4.09 | 0.136 | 0.46 | 1.214 | 4.11 |
| 4 | 240 | 44.070 | 0.870 | 1.97 | 1.635 | 3.71 | 0.000 | 0.00 | 1.852 | 4.20 | 0.478 | 1.08 | 1.913 | 4.34 |
| 5 | 240 | 61.342 | 0.974 | 1.59 | 2.791 | 4.55 | 0.000 | 0.00 | 2.956 | 4.82 | 0.474 | 0.77 | 2.994 | 4.88 |
| 6 | 240 | 69.433 | 1.444 | 2.08 | 3.209 | 4.62 | 0.000 | 0.00 | 3.519 | 5.07 | 0.289 | 0.42 | 3.531 | 5.09 |
| 7 | 240 | 25.510 | 0.420 | 1.65 | 0.924 | 3.62 | 0.000 | 0.00 | 1.015 | 3.98 | 0.177 | 0.69 | 1.030 | 4.04 |
| 8 | 240 | 14.865 | 0.236 | 1.59 | 0.203 | 1.37 | 0.091 | 0.61 | 0.324 | 2.18 | 0.000 | 0.00 | 0.324 | 2.18 |
| 9 | 240 | 25.030 | 0.402 | 1.61 | 0.890 | 3.56 | 0.000 | 0.00 | 0.977 | 3.90 | 0.196 | 0.78 | 0.996 | 3.98 |
| 10 | 240 | 14.929 | 0.263 | 1.76 | 0.139 | 0.93 | 0.148 | 0.99 | 0.332 | 2.23 | 0.000 | 0.00 | 0.332 | 2.22 |
| 11 | 240 | 37.850 | 0.625 | 1.65 | 1.188 | 3.14 | 0.000 | 0.00 | 1.342 | 3.55 | 0.408 | 1.08 | 1.403 | 3.71 |

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Image /page/8/Picture/0 description: The image contains the logo for Stago. The logo features the word "Stago" in a red, serif font. Above the word, there is an abstract graphic consisting of two curved shapes, one red and one brown, arranged in a circular pattern.

| STA Compact Max - All<br>lots (INR) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | | |
|-------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 1.0527 | 0.014 | 1.33 | 0.012 | 1.14 | 0.006 | 0.57 | 0.019 | 1.84 | 0.018 | 1.71 | 0.027 | 2.56 |
| 2 | 240 | 1.0321 | 0.016 | 1.55 | 0.019 | 1.84 | 0.010 | 0.97 | 0.027 | 2.59 | 0.016 | 1.55 | 0.032 | 3.10 |
| 3 | 240 | 2.2125 | 0.046 | 2.08 | 0.082 | 3.71 | 0.000 | 0.00 | 0.094 | 4.25 | 0.067 | 3.03 | 0.115 | 5.20 |
| 4 | 240 | 3.3475 | 0.067 | 2.00 | 0.129 | 3.85 | 0.000 | 0.00 | 0.145 | 4.34 | 0.144 | 4.30 | 0.204 | 6.09 |
| 5 | 240 | 4.7113 | 0.078 | 1.66 | 0.222 | 4.71 | 0.000 | 0.00 | 0.235 | 4.99 | 0.204 | 4.33 | 0.312 | 6.62 |
| 6 | 240 | 5.3553 | 0.115 | 2.15 | 0.257 | 4.80 | 0.000 | 0.00 | 0.282 | 5.26 | 0.237 | 4.43 | 0.368 | 6.87 |
| 10 | 240 | 1.0925 | 0.020 | 1.83 | 0.011 | 1.01 | 0.011 | 1.01 | 0.025 | 2.32 | 0.019 | 1.74 | 0.032 | 2.93 |

| STA Satellite - All lots<br>(seconds) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | | |
|---------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 14.108 | 0.139 | 0.99 | 0.218 | 1.55 | 0.000 | 0.00 | 0.259 | 1.83 | 0.112 | 0.79 | 0.282 | 2.00 |
| 2 | 240 | 13.639 | 0.165 | 1.21 | 0.202 | 1.48 | 0.000 | 0.00 | 0.261 | 1.91 | 0.136 | 1.00 | 0.294 | 2.16 |
| 3 | 240 | 29.791 | 0.439 | 1.47 | 0.731 | 2.45 | 0.000 | 0.00 | 0.853 | 2.86 | 0.000 | 0.00 | 0.853 | 2.86 |
| 4 | 240 | 44.366 | 0.695 | 1.57 | 0.983 | 2.22 | 0.313 | 0.71 | 1.244 | 2.80 | 0.563 | 1.27 | 1.366 | 3.08 |
| 5 | 240 | 64.173 | 0.688 | 1.07 | 2.063 | 3.21 | 0.227 | 0.35 | 2.187 | 3.41 | 0.666 | 1.04 | 2.286 | 3.56 |
| 6 | 240 | 71.376 | 1.334 | 1.87 | 2.307 | 3.23 | 0.000 | 0.00 | 2.665 | 3.73 | 0.590 | 0.83 | 2.730 | 3.82 |
| 7 | 240 | 24.988 | 0.267 | 1.07 | 0.505 | 2.02 | 0.000 | 0.00 | 0.571 | 2.29 | 0.000 | 0.00 | 0.571 | 2.29 |
| 8 | 240 | 14.557 | 0.221 | 1.52 | 0.242 | 1.66 | 0.081 | 0.56 | 0.338 | 2.32 | 0.025 | 0.17 | 0.339 | 2.33 |
| 9 | 240 | 25.170 | 0.345 | 1.37 | 0.709 | 2.82 | 0.000 | 0.00 | 0.788 | 3.13 | 0.000 | 0.00 | 0.789 | 3.13 |
| 10 | 240 | 14.665 | 0.140 | 0.95 | 0.172 | 1.17 | 0.070 | 0.48 | 0.233 | 1.59 | 0.074 | 0.50 | 0.244 | 1.66 |
| 11 | 240 | 38.025 | 0.559 | 1.47 | 1.211 | 3.18 | 0.000 | 0.00 | 1.334 | 3.51 | 0.266 | 0.70 | 1.360 | 3.58 |

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Image /page/9/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be two curved shapes, one red and one brown, arranged in a way that suggests movement or flow. The overall design is simple and modern.

| STA Satellite - All lots<br>(INR) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Total | | |
|-----------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 240 | 1.0383 | 0.011 | 1.06 | 0.016 | 1.54 | 0.000 | 0.00 | 0.019 | 1.87 | 0.009 | 0.87 | 0.022 | 2.12 |
| 2 | 240 | 1.0032 | 0.013 | 1.30 | 0.016 | 1.59 | 0.000 | 0.00 | 0.021 | 2.05 | 0.009 | 0.90 | 0.022 | 2.19 |
| 3 | 240 | 2.2549 | 0.034 | 1.51 | 0.057 | 2.53 | 0.000 | 0.00 | 0.066 | 2.94 | 0.042 | 1.86 | 0.079 | 3.50 |
| 4 | 240 | 3.4083 | 0.055 | 1.61 | 0.080 | 2.35 | 0.026 | 0.76 | 0.101 | 2.95 | 0.103 | 3.02 | 0.144 | 4.22 |
| 5 | 240 | 4.9968 | 0.055 | 1.10 | 0.166 | 3.32 | 0.014 | 0.28 | 0.175 | 3.51 | 0.163 | 3.26 | 0.240 | 4.80 |
| 6 | 240 | 5.5795 | 0.108 | 1.94 | 0.190 | 3.41 | 0.000 | 0.00 | 0.219 | 3.92 | 0.181 | 3.24 | 0.284 | 5.09 |
| 10 | 240 | 1.0812 | 0.012 | 1.11 | 0.013 | 1.20 | 0.006 | 0.55 | 0.019 | 1.73 | 0.013 | 1.20 | 0.022 | 2.03 |

Multi-site precision testing was performed over five days at three external sites per analyzer (STA R Max, STA Compact Max, and STA Satellite). 11 samples were tested across the measuring range, with two runs per day. Each run was at least two hours apart. The acceptance criteria were met for all samples in the studies.

| STA R Max - All sites - All<br>lots<br>(seconds) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | | |
|--------------------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|--------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 14.662 | 0.139 | 0.95 | 0.153 | 1.04 | 0.000 | 0.00 | 0.207 | 1.41 | 0.016 | 0.11 | 0.396 | 2.70 | 0.447 | 3.05 |
| 2 | 270 | 14.272 | 0.137 | 0.96 | 0.142 | 0.99 | 0.000 | 0.00 | 0.197 | 1.38 | 0.005 | 0.04 | 0.420 | 2.94 | 0.464 | 3.25 |
| 3 | 270 | 31.279 | 0.298 | 0.95 | 0.584 | 1.87 | 0.000 | 0.00 | 0.656 | 2.10 | 0.242 | 0.77 | 0.837 | 2.68 | 1.090 | 3.48 |
| 4 | 270 | 46.034 | 0.358 | 0.78 | 0.905 | 1.97 | 0.000 | 0.00 | 0.973 | 2.11 | 0.359 | 0.78 | 0.999 | 2.17 | 1.440 | 3.13 |
| 5 | 270 | 63.011 | 0.505 | 0.80 | 1.251 | 1.99 | 0.000 | 0.00 | 1.349 | 2.14 | 0.753 | 1.20 | 1.288 | 2.04 | 2.011 | 3.19 |
| 6 | 270 | 71.215 | 0.727 | 1.02 | 1.393 | 1.96 | 0.000 | 0.00 | 1.571 | 2.21 | 0.796 | 1.12 | 1.895 | 2.66 | 2.587 | 3.63 |
| 7 | 270 | 26.671 | 0.241 | 0.90 | 0.508 | 1.90 | 0.000 | 0.00 | 0.562 | 2.11 | 0.244 | 0.91 | 0.605 | 2.27 | 0.861 | 3.23 |
| 8 | 270 | 15.267 | 0.159 | 1.04 | 0.192 | 1.26 | 0.000 | 0.00 | 0.249 | 1.63 | 0.000 | 0.00 | 0.358 | 2.34 | 0.436 | 2.86 |
| 9 | 270 | 26.298 | 0.235 | 0.89 | 0.503 | 1.91 | 0.000 | 0.00 | 0.555 | 2.11 | 0.181 | 0.69 | 0.435 | 1.65 | 0.728 | 2.77 |
| 10 | 270 | 15.269 | 0.174 | 1.14 | 0.138 | 0.90 | 0.000 | 0.00 | 0.222 | 1.45 | 0.040 | 0.26 | 0.384 | 2.51 | 0.446 | 2.92 |
| 11 | 270 | 39.033 | 0.335 | 0.86 | 1.007 | 2.58 | 0.000 | 0.00 | 1.061 | 2.72 | 0.219 | 0.56 | 0.672 | 1.72 | 1.275 | 3.27 |

This document is property of DIAGNOSTICA STAGO. It cannot be communicated or copied without any prior authorization.

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Image /page/10/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be two curved shapes, one red and one brown, arranged in a way that suggests a stylized letter or symbol. The overall design is simple and modern.

| STA R Max - All sites - All<br>lots<br>(INR) | N | Mean | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | |
|----------------------------------------------|-----|--------|---------------|------|-------------|------|-------------|------|------------|------|-------------|------|--------------|------|-------|------|
| Sample | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 1.0724 | 0.010 | 0.93 | 0.012 | 1.12 | 0.000 | 0.00 | 0.016 | 1.46 | 0.016 | 1.49 | 0.029 | 2.70 | 0.036 | 3.36 |
| 2 | 270 | 1.0434 | 0.010 | 0.96 | 0.012 | 1.15 | 0.000 | 0.00 | 0.016 | 1.50 | 0.016 | 1.53 | 0.030 | 2.88 | 0.037 | 3.55 |
| 3 | 270 | 2.3474 | 0.023 | 0.98 | 0.046 | 1.96 | 0.000 | 0.00 | 0.051 | 2.19 | 0.048 | 2.04 | 0.059 | 2.51 | 0.092 | 3.92 |
| 4 | 270 | 3.5000 | 0.028 | 0.80 | 0.072 | 2.06 | 0.000 | 0.00 | 0.077 | 2.21 | 0.086 | 2.46 | 0.063 | 1.80 | 0.132 | 3.77 |
| 5 | 270 | 4.8404 | 0.041 | 0.85 | 0.100 | 2.07 | 0.000 | 0.00 | 0.108 | 2.23 | 0.116 | 2.40 | 0.084 | 1.74 | 0.180 | 3.72 |
| 6 | 270 | 5.4936 | 0.057 | 1.04 | 0.112 | 2.04 | 0.000 | 0.00 | 0.126 | 2.29 | 0.149 | 2.71 | 0.129 | 2.35 | 0.234 | 4.26 |
| 10 | 270 | 1.1189 | 0.013 | 1.16 | 0.011 | 0.98 | 0.000 | 0.00 | 0.017 | 1.52 | 0.015 | 1.34 | 0.028 | 2.50 | 0.036 | 3.22 |

| STA Compact Max - All<br>sites - All lots<br>(seconds) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | | |
|--------------------------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|--------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 14.622 | 0.182 | 1.24 | 0.186 | 1.27 | 0.094 | 0.64 | 0.277 | 1.89 | 0.126 | 0.86 | 0.276 | 1.89 | 0.411 | 2.81 |
| 2 | 270 | 14.291 | 0.182 | 1.27 | 0.242 | 1.69 | 0.000 | 0.00 | 0.303 | 2.12 | 0.138 | 0.97 | 0.171 | 1.20 | 0.374 | 2.62 |
| 3 | 270 | 30.786 | 0.604 | 1.96 | 0.645 | 2.10 | 0.107 | 0.35 | 0.890 | 2.89 | 0.294 | 0.95 | 1.283 | 4.17 | 1.589 | 5.16 |
| 4 | 270 | 45.475 | 0.627 | 1.38 | 1.098 | 2.41 | 0.414 | 0.91 | 1.330 | 2.93 | 0.292 | 0.64 | 1.241 | 2.73 | 1.843 | 4.05 |
| 5 | 270 | 62.711 | 0.917 | 1.46 | 1.773 | 2.83 | 0.582 | 0.93 | 2.079 | 3.32 | 0.000 | 0.00 | 1.665 | 2.66 | 2.664 | 4.25 |
| 6 | 270 | 70.780 | 1.379 | 1.95 | 2.379 | 3.36 | 0.000 | 0.00 | 2.750 | 3.88 | 0.621 | 0.88 | 2.317 | 3.27 | 3.649 | 5.16 |
| 7 | 270 | 26.370 | 0.411 | 1.56 | 0.563 | 2.14 | 0.000 | 0.00 | 0.697 | 2.64 | 0.500 | 1.90 | 0.850 | 3.22 | 1.207 | 4.58 |
| 8 | 270 | 15.233 | 0.182 | 1.19 | 0.237 | 1.56 | 0.000 | 0.00 | 0.299 | 1.96 | 0.113 | 0.74 | 0.323 | 2.12 | 0.454 | 2.98 |
| 9 | 270 | 26.111 | 0.436 | 1.67 | 0.558 | 2.14 | 0.000 | 0.00 | 0.708 | 2.71 | 0.229 | 0.88 | 0.902 | 3.45 | 1.170 | 4.48 |
| 10 | 270 | 15.190 | 0.174 | 1.15 | 0.266 | 1.75 | 0.000 | 0.00 | 0.318 | 2.09 | 0.103 | 0.68 | 0.248 | 1.63 | 0.416 | 2.74 |
| 11 | 270 | 39.131 | 0.544 | 1.39 | 0.926 | 2.37 | 0.000 | 0.00 | 1.074 | 2.74 | 0.381 | 0.97 | 1.199 | 3.06 | 1.654 | 4.23 |

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Image /page/11/Picture/0 description: The image contains the logo for Stago. The logo features the word "Stago" in a red, serif font. Above the word, there is an abstract graphic consisting of two curved shapes, one red and one brown, arranged in a circular fashion.

| STA Compact Max - All<br>sites - All lots<br>(INR) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | | |
|----------------------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|--------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 1.0695 | 0.014 | 1.31 | 0.014 | 1.31 | 0.008 | 0.75 | 0.021 | 2.00 | 0.026 | 2.43 | 0.016 | 1.50 | 0.038 | 3.55 |
| 2 | 270 | 1.0444 | 0.014 | 1.34 | 0.018 | 1.72 | 0.000 | 0.00 | 0.023 | 2.18 | 0.027 | 2.59 | 0.000 | 0.00 | 0.035 | 3.35 |
| 3 | 270 | 2.3103 | 0.046 | 1.99 | 0.050 | 2.16 | 0.007 | 0.30 | 0.068 | 2.96 | 0.085 | 3.68 | 0.088 | 3.81 | 0.140 | 6.06 |
| 4 | 270 | 3.4573 | 0.050 | 1.45 | 0.087 | 2.52 | 0.030 | 0.87 | 0.105 | 3.03 | 0.139 | 4.02 | 0.057 | 1.65 | 0.183 | 5.29 |
| 5 | 270 | 4.8191 | 0.073 | 1.51 | 0.143 | 2.97 | 0.043 | 0.89 | 0.166 | 3.45 | 0.189 | 3.92 | 0.074 | 1.54 | 0.262 | 5.44 |
| ଚି | 270 | 5.4617 | 0.111 | 2.03 | 0.193 | 3.53 | 0.000 | 0.00 | 0.223 | 4.08 | 0.236 | 4.32 | 0.131 | 2.40 | 0.350 | 6.41 |
| 10 | 270 | 1.1126 | 0.014 | 1.26 | 0.021 | 1.89 | 0.000 | 0.00 | 0.025 | 2.27 | 0.026 | 2.34 | 0.013 | 1.17 | 0.038 | 3.42 |

| STA Satellite - All sites -<br>All lots<br>(seconds) | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | | |
|------------------------------------------------------|-----|---------------|-------|-------------|-------|-------------|-------|------------|-------|-------------|-------|--------------|-------|-------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 14.370 | 0.166 | 1.16 | 0.203 | 1.41 | 0.000 | 0.00 | 0.262 | 1.82 | 0.196 | 1.36 | 0.225 | 1.57 | 0.397 | 2.76 |
| 2 | 270 | 13.957 | 0.130 | 0.93 | 0.216 | 1.55 | 0.000 | 0.00 | 0.252 | 1.81 | 0.200 | 1.43 | 0.223 | 1.60 | 0.392 | 2.81 |
| 3 | 270 | 31.016 | 0.510 | 1.64 | 1.039 | 3.35 | 0.000 | 0.00 | 1.157 | 3.73 | 0.534 | 1.72 | 1.251 | 4.03 | 1.786 | 5.76 |
| 4 | 270 | 46.346 | 0.600 | 1.29 | 1.110 | 2.40 | 0.000 | 0.00 | 1.262 | 2.72 | 0.744 | 1.61 | 1.484 | 3.20 | 2.085 | 4.50 |
| 5 | 270 | 66.456 | 0.829 | 1.25 | 1.457 | 2.19 | 0.212 | 0.32 | 1.690 | 2.54 | 0.836 | 1.26 | 1.893 | 2.85 | 2.672 | 4.02 |
| 6 | 270 | 74.733 | 1.331 | 1.78 | 2.262 | 3.03 | 0.000 | 0.00 | 2.625 | 3.51 | 1.455 | 1.95 | 3.260 | 4.36 | 4.432 | 5.93 |
| 7 | 270 | 25.763 | 0.387 | 1.50 | 0.532 | 2.06 | 0.000 | 0.00 | 0.658 | 2.55 | 0.180 | 0.70 | 0.776 | 3.01 | 1.033 | 4.01 |
| 8 | 270 | 14.878 | 0.220 | 1.48 | 0.241 | 1.62 | 0.000 | 0.00 | 0.326 | 2.19 | 0.229 | 1.54 | 0.385 | 2.59 | 0.554 | 3.72 |
| 9 | 270 | 25.845 | 0.372 | 1.44 | 0.573 | 2.22 | 0.000 | 0.00 | 0.683 | 2.64 | 0.375 | 1.45 | 0.741 | 2.87 | 1.075 | 4.16 |
| 10 | 270 | 14.926 | 0.154 | 1.03 | 0.229 | 1.53 | 0.000 | 0.00 | 0.276 | 1.85 | 0.180 | 1.21 | 0.309 | 2.07 | 0.452 | 3.03 |
| 11 | 270 | 39.160 | 0.618 | 1.58 | 1.013 | 2.59 | 0.000 | 0.00 | 1.187 | 3.03 | 0.848 | 2.17 | 1.130 | 2.89 | 1.845 | 4.71 |

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Image /page/12/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be three curved shapes, one red and one brown, arranged in a circular pattern.

| STA Satellite - All sites -<br>All lots<br>(INR) | | | Repeatability | | Between-run | | Between-day | | Within-lab | | Between_lot | | Between_site | | Total | |
|--------------------------------------------------|-----|--------|---------------|------|-------------|------|-------------|------|------------|------|-------------|------|--------------|------|-------|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 270 | 1.0587 | 0.012 | 1.13 | 0.016 | 1.51 | 0.000 | 0.00 | 0.020 | 1.89 | 0.020 | 1.89 | 0.015 | 1.42 | 0.032 | 3.02 |
| 2 | 270 | 1.0275 | 0.010 | 0.97 | 0.016 | 1.56 | 0.000 | 0.00 | 0.019 | 1.84 | 0.020 | 1.95 | 0.015 | 1.46 | 0.032 | 3.11 |
| 3 | 270 | 2.3522 | 0.039 | 1.66 | 0.082 | 3.49 | 0.000 | 0.00 | 0.091 | 3.86 | 0.088 | 3.74 | 0.088 | 3.74 | 0.154 | 6.55 |
| 4 | 270 | 3.5671 | 0.048 | 1.35 | 0.088 | 2.47 | 0.000 | 0.00 | 0.100 | 2.81 | 0.145 | 4.06 | 0.091 | 2.55 | 0.198 | 5.55 |
| 5 | 270 | 5.1826 | 0.068 | 1.31 | 0.117 | 2.26 | 0.014 | 0.27 | 0.136 | 2.63 | 0.204 | 3.94 | 0.105 | 2.03 | 0.267 | 5.15 |
| 6 | 270 | 5.8552 | 0.108 | 1.84 | 0.183 | 3.13 | 0.000 | 0.00 | 0.212 | 3.63 | 0.293 | 5.00 | 0.215 | 3.67 | 0.421 | 7.19 |
| 10 | 270 | 1.1012 | 0.012 | 1.09 | 0.018 | 1.63 | 0.000 | 0.00 | 0.022 | 1.96 | 0.023 | 2.09 | 0.021 | 1.91 | 0.038 | 3.45 |

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Image /page/13/Picture/0 description: The image shows the logo for Stago. The logo consists of the word "Stago" in red, with a stylized graphic above it. The graphic appears to be two curved shapes, one red and one brown, arranged in a way that suggests movement or flow. The overall design is simple and modern.

## Analytical Specificity/Interference

#### Extrinsic Factor Sensitivity

The study was performed to determine at which clinically significant abnormal extrinsic factor levels (Factor II, V, VII and X) the STA® - NeoPTimal gives abnormal results for PT. The study was performed using three lots on the STA-R family of analyzers.

| | STA NeoPTimal |
|------------|---------------|
| Factor II | 46 % |
| Factor V | 59 % |
| Factor VII | 55 % |
| Factor X | 65 % |

## Interferences

This study was performed to evaluate the effect of (endogenous or exogenous) potentially interfering substances in the STA - NeoPTimal assay on four samples;

- Patient sample included in the normal reference range
- VKA patient sample with an INR between 2.0 and 3.0
- VKA patient sample with an INR between 3.1 and 4.5 ●
- Deficient V patient sample

| Molecule | No interference up to |
|------------------------|-----------------------|
| Triglycerides | 3270 mg/dL |
| Hemoglobin | 4000 mg/dL |
| Conjugated Bilirubin | 29 mg/dL |
| Unconjugated Bilirubin | 20 mg/dL |
| UFH | 1.0 IU/mL |
| LMWH | 1.5 IU Anti-Xa/mL |
| Apixaban | 13 ng/mL |
| Dabigatran | 3 ng/mL |
| Edoxaban | 6 ng/mL |
| Rivaroxaban | 7 ng/mL |

#### Daptomycin

Note: According to the drug manufacturer, Daptomycin may artificially prolong PT and INR in patients with normal renal function for up to nine hours and for patients with renal impairment up to 28 hours'. Therefore, PT or INR monitoring of patients on Daptomycin may be affected for up to 28 hours after dosing.

#### Stability

#### Sample Stability – Room Temperature

A study of sample stability at room temperature was performed to demonstrate plasma remains stable for 24 hours if stored at room temperature. Four normal samples and eight VKA samples with INR between 1.5 to 5.5 were used along with one lot of STA NeoPTimal. Samples were testing in triplicate for each sample across different time points. All results met the acceptance criteria and support a plasma stability claim of 24 hours at room temperature.

¹ PATEL S., SAW S. Daptomycin. [Updated 2020 Apr 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470407

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Image /page/14/Picture/0 description: The image contains the logo for Stago. The logo features the word "Stago" in a red, serif font. Above the word "Stago" is an abstract graphic consisting of two curved shapes, one red and one brown, arranged in a circular fashion. The red shape is positioned above the brown shape.

## Sample Stability - Long-term Frozen

The study was performed across two lots of STA® - NeoPTimal on a STA-R family analyzer. Testing was performed on 53 samples stored at ≤ -70°C;

- -Patient samples included in the normal reference range (Normal)
- VKA patient samples with INR between 1.5 and 5.0 -

All samples were tested in triplicate at different time points. All results met the acceptance criteria and support a long-term frozen plasma stability claim of 12 months at ≤ -70℃.

#### Shelf-life Stability

The study was performed on three lots of each STA® - NeoPTimal configuration on a STA-R family analyzer. Testing was performed on 10 samples;

- Patient samples included in the normal reference range (Normal) -
- -VKA patient samples with INR between 2 and 4.5
- Deficient V patient samples -
- Quality controls -

All samples were tested in triplicate at different time points. The results support the following shelf-life when stored at 2-8°C:

| Product | Shelf-Life Stability Claim |
|----------------------|----------------------------|
| STA – NeoPTimal (5) | 24 months |
| STA – NeoPTimal (10) | 24 months |

## In-Use Stability

The study was performed on three lots of STA - NeoPTimal representing the two different volume configurations (5ml and 10ml) on the STA-R family, STA Compact family and STA Satellite instrumentation. Testing was performed on six samples:

- Patient sample included in the normal reference range (Normal) .
- VKA patient sample with an INR between 2.0 and 3.0 (VKA 2-3) .
- VKA patient sample with an INR between 3.1 and 4.5 (VKA 3-4.5) .
- . Deficient patient sample (Def V)
- Two controls .

All the samples were tested after reconstitution (TOh) in triplicate at different time points. The result support the following:

| | STA® - NeoPTimal 5 | STA® - NeoPTimal 10 |
|--------------------------------------|--------------------|---------------------|
| STA-R® family<br>STA Compact® family | 48h on board | |
| STA Satellite® family | | 4 days on board |
| 2-8 °C | 8 days | |

Detection Limit Not applicable

Assay Cut-off Not applicable

{15}------------------------------------------------

Image /page/15/Picture/0 description: The image contains the logo for Stago. The logo features the word "Stago" in red, serif font. Above the word is an abstract graphic consisting of two curved shapes. The top shape is red, and the bottom shape is brown. The shapes are arranged in a way that suggests movement or rotation.

## Comparison Studies

### Method Comparison

Four sites were involved in the external method comparison study for STA – NeoPTimal to validate the performance of the STA - NeoPTimal kit via method comparison with the predicate device, Thromborel S across one STA R Max, STA Satellite, STA Compact Max, and three Siemens CA-1500s. The STA NeoPTimal performed comparably to the Thromborel S. All acceptance criteria were met.

| Slope<br>(95% CI) | Intercept<br>(95% CI) | rPearson |
|------------------------|------------------------|----------|
| 0.93<br>(0.92 to 0.95) | 0.04<br>(0.02 to 0.06) | 0.965 |

| Bias at 2.5 INR<br>(95% CI) | Bias at 3.5 INR<br>(95% CI) |
|-----------------------------|-----------------------------|
| -5.3% | -5.7% |
| (-6.2% to -4.3%) | (-6.9% to -4.6%) |

## Clinical Studies

Clinical Sensitivity Not applicable

Clinical Specificity Not applicable

Clinical Cut-off Not applicable

#### Reference Interval

The adult reference interval was based on calculations established within CLSI guideline EP28-A3c using 137 patients across three external sites. The reference interval for STA® -NeoPTimal was determined to be 11.8 to 14.9 seconds, and 0.89 to 1.11 INR.

## CONCLUSION

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.