(258 days)
The QNext is a fully-automated, random-access instrument, intended for in vitro diagnostic use in clinical laboratories to perform hemostasis testing by detecting the changes in optical density.
DG-PT is a thromboplastin reagent for the quantitative determination of Prothrombin Time on human plasma samples collected in 3.2% sodium citrate.
The product is used for the evaluation of the extrinsic and common coagulation pathways in seconds and for the monitoring Oral Anticoagulant Therapy with warfarin in International Normalized Ratio (INR).
For use with ONext.
For clinical professional laboratory and prescription use only.
For in vitro diagnostic use.
The performance of this device has not been established in neonate and pediatric patient populations.
QNext is designed to automatically perform all stages of the procedures associated to hemostasis tests allowing the operator to:
- Absorb the workload involved in running hemostasis laboratory tests profiles, optimizing the execution of these profiles in the shortest time possible, and ensuring the maximum possible precision and accuracy in the results.
- Increase the reliability of the analytical process, eliminating any possible errors in the identification ● and treatment of samples and products and in the revision and transcription of the results.
- Reduce the risk of Operator contamination by minimizing interaction between the Operator and ● samples and products during the analytical process.
To perform the operations for which it has been designed, QNext automatically follows the steps listed below:
- Sample management: loading, positive identification, dilution (if required) and dispensation into cuvettes.
- Reagent management: loading, positive identification, cooling, stirring, aspiration and dispensation into cuvettes.
- Cuvette management: loading, transport, incubation during the reactions and management of used cuvettes.
- Management of test requests. ●
- Execution of test procedures.
- Result management: optical measurement of the reactions, algorithm calculation of analytical parameters from reaction curves, validation of results, traceability, bi-directional transmission of requests and results to the LIS.
- Management of disposable components. ●
The data analyzed can be stored, displayed and printed. Additionally, the analyzer allows conducting integrated functions, such as the analysis of urgent samples or the Quality Control module.
DG-PT consists of a glass vial containing lyophilized thromboplastin (tissue factor and phospholipids) from rabbit brain tissue, buffer, calcium ions and preservative. The closure system includes a stopper and a screw сар.
DG-PT reagent is used to perform PT tests for:
- the evaluation of the extrinsic and common coagulation pathways.
- The monitoring Oral Anticoagulant Therapy with warfarin.
The assay is based on the activation of the extrinsic coagulation pathway by the addition of the reagent to the plasma sample. The thromboplastin interacts with FVII and calcium ions activating a series of specific enzymes that comprise the extrinsic and common pathways of the coagulation cascade ultimately leading to the formation of a fibrin clot. The QNext reader measures the light change produced during the reaction.
The provided text describes the performance testing of the ONext instrument and DG-PT reagent for Prothrombin Time (PT) determination, but it does not contain information related to an AI/ML powered device. Therefore, many of the requested criteria regarding AI/ML device performance (e.g., multi-reader multi-case studies, human-in-the-loop performance, training set details, expert ground truth adjudication) are not applicable to this document.
However, I can extract and present the acceptance criteria and performance data for the described in-vitro diagnostic device:
Device: ONext (fully-automated hemostasis instrument) and DG-PT (thromboplastin reagent for PT determination).
Study Proving Device Meets Acceptance Criteria:
The submission details several performance studies conducted according to CLSI guidelines to demonstrate the substantial equivalence of the ONext and DG-PT to predicate devices.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined quantitative acceptance criteria thresholds for each study (e.g., "Precision CV must be less than X%"). Instead, it presents the results of various performance studies (Precision, Reference Interval, Sensitivity, Specificity, Method Comparison) which are implicitly understood to meet the necessary performance characteristics for substantial equivalence. The "performance" column therefore reflects the observed results from these studies.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (ONext and DG-PT) |
|---|---|---|
| Precision | Repeatability and Within-laboratory precision should demonstrate acceptable variability. | Repeatability (PT seconds / INR): Varies by sample level. For PT (seconds), 1.4-2.1% CV; for INR, 1.6-2.4% CV. Upper One-sided 95% Limits slightly higher. Within-laboratory Precision (PT seconds / INR): Varies by sample level. For PT (seconds), 2.4-5.7% CV; for INR, 2.2-8.2% CV. Upper One-sided 95% Limits higher. Reproducibility (PT seconds / INR): Varies by sample level. For PT (seconds), Repeatability 1.6-3.1% CV, Reproducibility 3.1-6.0% CV; for INR, Repeatability 1.9-3.7% CV, Reproducibility 5.5-9.2% CV. Upper One-sided 95% Limits higher. (See Tables 1 & 2 in source for full details) |
| Reference Interval | Establish a clear reference interval for healthy individuals. | PT (seconds): 12.1 to 16.1 seconds PT (INR): 0.83 to 1.17 INR |
| Sensitivity (Factor) | Demonstrate ability to detect deficiencies in key coagulation factors. | FII: 29 IU/dL FV: 45 IU/dL FVII: 44 IU/dL FX: 43 IU/dL |
| Specificity (Interference) | Demonstrate resistance to interference from common endogenous and exogenous substances. | Maximum Concentration without Significant Interference (Normal/Abnormal samples): Hemoglobin: 10.0 g/L Conjugated bilirubin: 43.3 mg/dL Triglycerides: 3000 mg/dL Citrate: 0.6% UFH: 1.1 IU/mL (Normal), 0.7 IU/mL (Abnormal) LMWH: 2.3 IU/mL (Normal), 1.8 IU/mL (Abnormal) Observed Interference at All Concentrations Tested for: Rivaroxaban (e.g., 313, 625, 938, 1250 ng/mL for normal sample) Argatroban (e.g., 375, 750, 1125, 1500 ng/mL for normal sample) Dabigatran (e.g., 150, 300, 450, 600 ng/mL for normal sample) |
| Method Comparison | Results should correlate well with a legally marketed predicate device. | Results from two US sites (n=360): PT (s): Slope 0.913 (95% CI: 0.893-0.938), Intercept 1.118 (95% CI: 0.706-1.477), r=0.983 PT (INR): Slope 1.034 (95% CI: 1.010-1.060), Intercept -0.024 (95% CI: -0.054-0.009), r=0.980 Results from ex-US site (n=271): PT (s): Slope 0.985 (95% CI: 0.962-1.003), Intercept 0.272 (95% CI: -0.078-0.716), r=0.988 PT (INR): Slope 1.000 (95% CI: 0.978-1.022), Intercept -0.070 (95% CI: -0.099--0.042), r=0.990 |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Studies:
- Repeatability and Within-laboratory: 7 patient-derived samples. Data provenance not explicitly stated (e.g., country of origin), assumed to be clinical samples. Retrospective/prospective not specified, but typically for precision studies, these would be collected prospectively or obtained from a biobank.
- Reproducibility: 7 patient-derived samples. Data provenance not explicitly stated (e.g., country of origin), assumed to be clinical samples. Retrospective/prospective not specified.
- Reference Interval Study: 243 reference samples. Data provenance not explicitly stated.
- Sensitivity Study: Not specified, but involved a set of samples spanning from 100% to <1% of specific coagulation factors.
- Specificity Study: Two sample levels (pooled normal and pooled abnormal samples) with various interfering substances added. Specific total sample count not given.
- Method Comparison Study:
- US Sites: 360 patient-derived samples covering the claimed analytical measurement range (AMR). Data provenance: from two US clinical sites.
- Ex-US Site: 271 patient-derived samples covering the claimed AMR. Data provenance: from one ex-US clinical site.
- Retrospective/Prospective: Not explicitly stated, but clinical validation studies often use prospectively collected samples or samples from a well-characterized biobank.
3. Number of Experts Used to Establish Ground Truth and Qualifications
Not Applicable. This is an in-vitro diagnostic device for measuring Prothrombin Time. The "ground truth" is established by direct measurement of the blood coagulation time or the INR, not by expert interpretation of images or clinical data. Therefore, expert consensus for ground truth is not relevant to this type of device.
4. Adjudication Method for the Test Set
Not Applicable. As per point 3, the ground truth for this device is a direct quantitative measurement, not a subjective interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, If So, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance
Not Applicable. This document describes a medical device for in-vitro diagnostics (measuring blood coagulation), not an AI/ML powered device for image interpretation or diagnosis. There are no "human readers" or "AI assistance" components mentioned in the context of this device's intended use or validation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Not Applicable. This is not an AI/ML algorithm. The device, ONext, is a fully-automated instrument, meaning its performance is inherently "standalone" in terms of its operation and measurement of PT/INR. The "human-in-the-loop" would be the laboratory professional using the instrument, but their role is in operating the device and interpreting its quantitative output, not in assisting or being assisted by an algorithm in a diagnostic task.
7. The Type of Ground Truth Used
The "ground truth" for the performance studies of the ONext and DG-PT device is:
- Direct Measurement: The actual PT/INR values obtained from patient samples using the predicate device or a reference method.
- Clinical Samples with Known Characteristics: For sensitivity studies, samples with known factor deficiencies were used. For specificity studies, samples with known concentrations of interfering substances were used.
- Reference Intervals: Established from healthy donor samples.
8. The Sample Size for the Training Set
Not Applicable. As this is not an AI/ML powered device, there is no "training set" in the context of machine learning model development. The device's operational parameters and algorithms are determined through traditional engineering and chemistry principles, not data-driven machine learning training.
9. How the Ground Truth for the Training Set was Established
Not Applicable. See point 8.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 21, 2019
Diagnostic Grifols, S.A. Joaquin Tamparillas Technical Director at Diagnostic Industrial Group of Grifols S.A. Passeig Fluvial, 24 Parets del Valles, Barcelona 08150 Spain
Re: K183390
Trade/Device Name: ONext and DG-PT Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA, GJS Dated: July 20, 2019 Received: July 22, 2019
Dear Joaquin Tamparillas:
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.
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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 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 mediation-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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Takeesha Taylor-Bell Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K183390
Device Name QNext and DG-PT
Indications for Use (Describe)
QNext:
The QNext is a fully-automated, random-access instrument, intended for in vitro diagnostic use in clinical laboratories to perform hemostasis testing by detecting the changes in optical density.
DG-PT:
DG-PT is a thromboplastin reagent for the quantitative determination of Prothrombin Time on human plasma samples collected in 3.2% sodium citrate.
The product is used for the evaluation of the extrinsic and common coagulation pathways in seconds and for the monitoring Oral Anticoagulant Therapy with warfarin in International Normalized Ratio (INR).
For use with ONext.
For clinical professional laboratory and prescription use only.
For in vitro diagnostic use.
The performance of this device has not been established in neonate and pediatric patient populations.
| Type of Use (Select one or both, as applicable): |
|---|
| Research Use Only (Per 21 CFR 201.122 - Sponsor-Investigator) |
| For-Profit Commercial Use (Per 21 CFR 201.128 - Sponsor-Investigator) |
Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
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510 (k) Summary
This 510(k) Summary of Safety and Effectiveness is submitted in accordance with the requirements of 21 CFR 807.92 and follows the FDA guidance 'The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]', issued July 28, 2014.
5.1 Submitter Information
| Company Information: | Diagnostic Grifols S.A.Passeig Fluvial, 24, Parets del VallesBarcelona, 08150, Spain |
|---|---|
| Contact Person: | Joaquín Alberto Tamparillas, GH Diagnostic Techical DirectorPhone: (34) 670 924 632Fax: (34) 935 731 132Email: joaquin.alberto@grifols.com |
| Date Prepared: | June 13, 2019 |
5.2 Devices
| Trade Names: | QNext and DG-PT. |
|---|---|
| Common Names: | Multipurpose System for In Vitro Coagulation and Prothrombin Time. |
| Regulation Number: | 864.5425 and 864.7750 |
| Regulatory Class: | Class II |
| Product Codes: | JPA and GJS |
5.3 Predicate Devices
| Trade Names: | ACL Top 700 (K160276) and HemosIL PT Fibrinogen HS Plus(K060931). |
|---|---|
| Common Names: | Instrument Coagulation Automated and Prothrombin Time. |
| Regulation Number: | 864.5400 and 864.7750 |
| Regulatory Class: | Class II |
| Product Codes: | GKP and GJS |
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5.4 Device Description
QNext is designed to automatically perform all stages of the procedures associated to hemostasis tests allowing the operator to:
- Absorb the workload involved in running hemostasis laboratory tests profiles, optimizing the execution of these profiles in the shortest time possible, and ensuring the maximum possible precision and accuracy in the results.
- Increase the reliability of the analytical process, eliminating any possible errors in the identification ● and treatment of samples and products and in the revision and transcription of the results.
- Reduce the risk of Operator contamination by minimizing interaction between the Operator and ● samples and products during the analytical process.
To perform the operations for which it has been designed, QNext automatically follows the steps listed below:
- Sample management: loading, positive identification, dilution (if required) and dispensation into cuvettes.
- Reagent management: loading, positive identification, cooling, stirring, aspiration and dispensation into cuvettes.
- Cuvette management: loading, transport, incubation during the reactions and management of used cuvettes.
- Management of test requests. ●
- Execution of test procedures.
- Result management: optical measurement of the reactions, algorithm calculation of analytical parameters from reaction curves, validation of results, traceability, bi-directional transmission of requests and results to the LIS.
- Management of disposable components. ●
The data analyzed can be stored, displayed and printed. Additionally, the analyzer allows conducting integrated functions, such as the analysis of urgent samples or the Quality Control module.
DG-PT consists of a glass vial containing lyophilized thromboplastin (tissue factor and phospholipids) from rabbit brain tissue, buffer, calcium ions and preservative. The closure system includes a stopper and a screw сар.
DG-PT reagent is used to perform PT tests for:
- the evaluation of the extrinsic and common coagulation pathways.
- The monitoring Oral Anticoagulant Therapy with warfarin.
The assay is based on the activation of the extrinsic coagulation pathway by the addition of the reagent to the plasma sample. The thromboplastin interacts with FVII and calcium ions activating a series of specific enzymes that comprise the extrinsic and common pathways of the coagulation cascade ultimately leading to the formation of a fibrin clot. The QNext reader measures the light change produced during the reaction.
{5}------------------------------------------------
ર્સ્ડ Indications for Use
QNext:
The QNext is a fully-automated, random-access instrument, intended for in vitro diagnostic use in clinical laboratories to perform hemostasis testing by detecting the changes in optical density.
DG-PT:
DG-PT is a thromboplastin reagent for the quantitative determination of Prothrombin Time on human plasma samples collected in 3.2% sodium citrate.
The product is used for the evaluation of the extrinsic and common coagulation pathways in seconds and for the monitoring Oral Anticoagulant Therapy with warfarin in International Normalized Ratio (INR). For use with QNext.
For clinical professional laboratory and prescription use only.
For in vitro diagnostic use.
The performance of this device has not been established in neonate and pediatric patient populations.
ર્સ્વ Comparison to Predicate Devices
5.6.1 Similarities
| Item | Subject DeviceQNext | Predicate DeviceACL Top 700 |
|---|---|---|
| Intended Use | The QNext is a fully-automated, random-access instrument, intended for in vitro diagnostic use in clinical laboratories to perform hemostasis testing by detecting the changes in optical density. | The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurements and calculated parameters. |
| Specimen type | 3.2% Citrated Plasma | Same |
| Methodology | Cloting tests.Note: QNext doesn't include the chromogenic and turbidimetric methods in the intended use. This indication will be presented in a future 510(k) submission. | - Cloting tests.- Chromogenic- Turbidimetric |
| Quality Control | Automated QC | Same |
| Modes ofOperation | Automated and continuous | Same |
| Cuvettesloading | Continuous | Same |
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| Item | Subject DeviceQNext | Predicate DeviceACL Top 700 |
|---|---|---|
| Samples andReagents barcode reader | Yes | Same |
| Sample pre-dilution | Yes | Same |
| Sample liquidlevel detection | Yes | Same |
| Reagentcontainer | Original container | Same |
| Item | Subject Device | Predicate Device | |
|---|---|---|---|
| DG-PT | HemosIL PT-Fibrinogen HS PLUS | ||
| Intended Use | DG-PT is a thromboplastin reagent forthe quantitative determination ofProthrombin Time on human plasmasamples collected in 3.2% sodium citrate.The product is used for the evaluation ofthe extrinsic and common coagulationpathways in seconds and for themonitoring Oral Anticoagulant Therapywith warfarin in InternationalNormalized Ratio (INR). For use withQNext. For clinical professionallaboratory and prescription use only. Forin vitro diagnostic use. The performanceof this device has not been established inneonate and pediatric patient populations.Note: DG-PT doesn't include thedetermination of fibrinogen in theintended use. This indication will bepresented in a future 510(k) submission. | A very high sensitivity calciumthromboplastin for simultaneousdeterminations of Prothrombin Time (PT)and Fibrinogen (Fib), for the evaluation ofthe extrinsic coagulation pathway andmonitoring Oral Anticoagulant Therapy inhuman citrated plasma on the ILCoagulation Systems. | |
| Principle of thetest | The assay is based on the activation ofthe extrinsic coagulation pathway by theaddition of a PT reagent to plasma.Tissue thromboplastin interacts withFVII and calcium ions activating a seriesof specific enzymes that comprise theextrinsic and common pathways of thecoagulation cascade, ultimately leadingto the formation of a fibrin clot.The PT is the time (in seconds) from themixing of the plasma with athromboplastin reagent until a fibrin clotis detected | Same |
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| Vial content | Lyophilized | Same |
|---|---|---|
| Thromboplastin origin | Rabbit brain | Same |
| Reagent preparation required | Yes. Reconstitution | Same |
| Device Class | 2 | Same |
| Classification Product Code | GJS; CFR 864.7750 | Same |
| Common Name | Test, Time, Prothrombin | Same |
| Measurement | Quantitative | Same |
| Detection principle | Photometric | Same |
| Sample Type | Citrated plasma | Same |
| Reporting units | PT: seconds and INR | Same |
5.6.2 Differences
| Item | Subject DeviceQNext | Predicate DeviceACL Top 700 |
|---|---|---|
| Regulatory | JPA, Class II864.5425 Multipurpose System For In | GKP, Class II864.5400 Instrument, coagulation, |
| Classification | Vitro Coagulation | automated |
| Samples on- | 60 | 120 |
| board | ||
| Reagents on- | 30 | 60 |
| board | ||
| Wavelength | 405 nm and/or 620 nm | 405 nm and/or 671 nm |
| Item | Subject Device DG-PT | Predicate Device PT-Fibrinogen HSPLUS |
| Package content | 6 vials of Thromboplastin | 5 vials of Thromboplastin |
| 5 vials of Buffer. | ||
| Quality control | 2 levels | 3 levels |
| In-use | Stability after reconstitution, stored at 2- | Stability after reconstitution, stored at 2-8 |
| Stability | 8 ℃ in the original vial: 10 days. | ℃ in the original vial: 5 days. |
| On-board stability: 5 days. | On-board stability: 36 hours. |
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5.7 Performance Testing
5.7.1 Precision
Precision studies were designed in accordance with CLSI EP05-A3.
Repeatability and Within-laboratory precision study was performed in a single site involving seven patient derived samples with tree lots of reagent during twenty days with two runs per day and two replicates per run.
Reproducibility study was performed in three sites assaying seven patient derived samples on two instruments during five days with two runs per day and three replicates per run.
The following results were demonstrated:
| Sample | Mean Value | N | Repeatability | Within-laboratory | |||
|---|---|---|---|---|---|---|---|
| Test | %CV | Upper One-sided 95% Limit | %CV | Upper One-sided 95% Limit | |||
| Prothrombin time(seconds) | 1 | 10.65 | 240 | 1.4 | 1.6 | 2.4 | 3.3 |
| 2 | 17.02 | 238 | 1.6 | 1.8 | 3.5 | 5.1 | |
| 3 | 27.68 | 240 | 1.7 | 1.9 | 3.6 | 6.3 | |
| 4 | 29.40 | 240 | 1.9 | 2.1 | 3.4 | 5.9 | |
| 5 | 37.48 | 240 | 1.8 | 2.0 | 3.9 | 8.6 | |
| 6 | 53.82 | 240 | 1.7 | 1.9 | 4.4 | 10.4 | |
| 7 | 85.08 | 240 | 2.1 | 2.3 | 5.7 | 15.5 | |
| Prothrombin time(INR) | 1 | 0.729 | 240 | 1.6 | 1.8 | 2.2 | 2.4 |
| 2 | 1.250 | 238 | 1.7 | 1.9 | 3.9 | 5.6 | |
| 3 | 2.186 | 240 | 2.0 | 2.2 | 4.4 | 8.3 | |
| 4 | 2.343 | 240 | 2.2 | 2.5 | 4.5 | 9.8 | |
| 5 | 3.098 | 240 | 2.0 | 2.3 | 5.3 | 13.4 | |
| 6 | 4.698 | 240 | 2.0 | 2.3 | 6.2 | 17.4 | |
| 7 | 7.959 | 240 | 2.4 | 2.7 | 8.2 | 26.2 |
Table 1. Summary of Repeatability and Within-Laboratory Precision Study Results
CV=Coefficient of Variation
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| Test | Sample | MeanValue | N | Repeatability | Reproducibility | ||
|---|---|---|---|---|---|---|---|
| %CV | Upper One-sided95% Limit | %CV | Upper One-sided95% Limit | ||||
| Prothrombin time(seconds) | 1 | 10.70 | 180 | 2.2 | 2.5 | 3.1 | 4.0 |
| 2 | 16.78 | 180 | 1.6 | 1.8 | 3.1 | 4.2 | |
| 3 | 27.08 | 180 | 1.9 | 2.1 | 4.2 | 6.1 | |
| 4 | 29.06 | 180 | 1.7 | 1.9 | 4 | 6.1 | |
| 5 | 36.87 | 180 | 1.7 | 1.9 | 4 | 8.3 | |
| 6 | 52.27 | 180 | 1.7 | 1.9 | 5.7 | 9.1 | |
| 7 | 80.65 | 180 | 3.1 | 3.4 | 6 | 13.1 | |
| Prothrombin time(INR) | 1 | 0.712 | 180 | 2.6 | 2.9 | 5.5 | 11.3 |
| 2 | 1.212 | 180 | 1.9 | 2.1 | 5.5 | 10.9 | |
| 3 | 2.133 | 180 | 2.2 | 2.5 | 6.9 | 13.9 | |
| 4 | 2.318 | 180 | 2.1 | 2.3 | 6.9 | 14.4 | |
| 5 | 3.070 | 180 | 2 | 2.2 | 6.7 | 17.3 | |
| 6 | 4.637 | 180 | 2 | 2.3 | 8.7 | 18.3 | |
| 7 | 7.735 | 180 | 3.7 | 4.1 | 9.2 | 24.7 |
Table 2. Summary of Reproducibility Study Results
CV=Coefficient of Variation
5.7.2 Reference Interval Study
The reference interval study was designed in accordance with CLSI C28-A3.
The study was performed at two sites using one lot of reagents. A total of 243 reference samples were tested with each reagent.
The Reference Intervals of DG-PT in seconds and INR are shown in the following tables:
| Test(units) | Reference Interval |
|---|---|
| Prothrombin time (seconds) | 12.1 to 16.1 |
| Prothrombin time (INR) | 0.83 to 1.17 |
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5.7.3. Sensitivity Study
Factor sensitivity study was designed in accordance with CLSI H47-A2. DG-PT Prothrombin Time determination was made for factors II, V, VII and X in a set of samples spanning from 100% to <1% of a specific coagulation factor, in order to establish the minimum concentration at which the screening test rises above the upper limit of the established reference interval.
The sensitivity results of Prothrombin Time to factor deficiency (II, V, VII and X) plasmas are provided below:
| Sensitivity (IU/dL) | |
|---|---|
| FII | 29 |
| FV | 45 |
| FVII | 44 |
| FX | 43 |
5.7.4. Specificity Study
The study was designed in accordance with the recommendations in CLSI EP7-A2 and the statistical analyses were conducted in accordance with the recommendations in CLSI EP7-A3.
Two sample levels were tested (pooled normal samples and pooled abnormal samples). Each potentially interfering substance was added to the sample pool. The interfering was conducted by paireddifference.
Maximum concentration of interfering substances for DG-PT Prothrombin Time is summarized in the following tables:
| Normal level | Abnormal level | |||
|---|---|---|---|---|
| Interfering substance / Test | PT (s) | PT (INR) | PT (s) | PT (INR) |
| Hemoglobin (g/L) | 10.0 | 10.0 | 10.0 | 10.0 |
| Conjugated bilirubin (mg/dL) | 43.3 | 43.3 | 43.3 | 43.3 |
| Triglycerides (mg/dL) | 3000 | 3000 | 3000 | 3000 |
| Citrate (%) | 0.6 | 0.6 | 0.6 | 0.6 |
| UFH (IU/mL) | 1.1 | 0.9 | 0.7 | 0.7 |
| LMWH (IU/mL) | 2.3 | 2.0 | 1.8 | 1.6 |
{11}------------------------------------------------
Interference of argatroban, dabigatran and rivaroxaban was observed at all concentrations tested indicated below:
| Rivaroxaban(ng/mL) | Argatroban(ng/mL) | Dabigatran(ng/mL) | |
|---|---|---|---|
| Normal sample | 313, 625, 938, 1250 | 375, 750, 1125, 1500 | 150, 300, 450, 600 |
| Abnormal sample | 156, 313, 469, 625 | 150, 300, 450, 600 | 75, 150, 225, 300 |
5.7.5. Method comparison Study
This study was designed in accordance with CLSI EP09-A3. Method comparison study was conducted at three clinical sites. For each test, a minimum of 100 patient derived samples covering the claimed analytical measurement range (AMR) were tested at each site. Samples were assayed in a parallel, testing on both systems: QNext with DG-PT and the predicate device ACL Top 700 with HemosIL PT Fibrinogen HS Plus. The regression results are summarized in the following tables:
Results from the two US sites:
| Assay | n | Slope (95% CI) | Intercept (95% CI) | r |
|---|---|---|---|---|
| PT (seconds) | 360 | 0.913 (0.893-0.938) | 1.118 (0.706 - 1.477) | 0.983 |
| PT (INR) | 360 | 1.034 (1.010 - 1.060) | -0.024 (-0.054 - 0.009) | 0.980 |
CI=Confidence interval
Results from the ex-US site:
| Assay | n | Slope (95% CI) | Intercept (95% CI) | r |
|---|---|---|---|---|
| PT (seconds) | 271 | 0.985 (0.962-1.003) | 0.272 (-0.078 - 0.716) | 0.988 |
| PT (INR) | 271 | 1.000 (0.978 - 1.022) | -0.070 (-0.099 --0.042) | 0.990 |
CI=Confidence interval
10.9 Conclusions
Diagnostic Grifols S.A based on all the information included and discussed in this submission concludes that QNext and DG-PT are substantially equivalent to the predicate devices. The information submitted to FDA demonstrates that the devices are at least as safe and effective as the legally marketed devices.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.