(219 days)
CP3000 analyzer: The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays.
Coagpia AT Reagent: Coagpia AT Reagent is intended for the quantitative determination (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use.
Coagpia Calibrator: The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. - Coagpia AT Reagent
Coagpia Control Set: The Coagpia Control Set contains 2 levels of assaved plasma intended for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. - Coagpia AT Reagent
CP3000: The CP3000 is designed for easy-to-use, rapid in-vitro blood coagulation testing on citrated human plasma. The CP3000 system is capable of performing the chromogenic methodologic assay, giving the user the ability to perform analysis for both direct hemostasis measurements and calculated parameters. For these assay methodologies, the analyzers employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405/570/730 nm.
Coagpia AT Reagent: Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzers. The reagent is supplied in a kit of 2 x 10 mL of Reagent 1 and 1 x 10mL of Reagent 2. Both reagents are liquid and do not require any preparation prior to use.
Coagpia Calibrator: The Coagpia Calibrator is supplied as 10 vials of lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzers.
Coagpia Control Set: The Coagpia Control Set is supplied as10 vials of lyophilized human plasma; 5 vials of Level 1 Control and 5 vials of Level 2 Control and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzers.
Here's a breakdown of the acceptance criteria and study information for the CP3000 Coagulation analyzer, Coagpia AT Reagent, Coagpia Calibrator, and Coagpia Control Set, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (New Device) | Reported Device Performance (Coagpia AT Reagent on CP3000) |
|---|---|---|
| Precision (Coagpia AT Reagent) | ||
| Repeatability (Within-Run) CV | ≤ 10% | 0.7% - 2.9% |
| Between-Run CV | ≤ 10% | 0.8% - 5.1% |
| Between-Day CV | ≤ 10% | 0.0% - 0.4% |
| Between-Lot CV | ≤ 10% | 0.3% - 1.0% |
| Within-Laboratory CV | ≤ 10% | 1.1% - 5.8% |
| Between Instrument CV | ≤ 15% | 0.6% - 4.8% |
| Total CV | ≤ 15% | 1.3% - 7.7% |
| Analytical Sensitivity | ||
| Limit of Quantitation (LOQ) | Total error ≤ 15% | 11% |
| Limit of Blank (LOB) | Not explicitly stated | 3% |
| Limit of Detection (LOD) | Not explicitly stated | 5% |
| Linearity | Allowable non linearity < 20% | 14% - 140% |
| Clinical Reportable Range (CRR) | Design goal of 150% | 14% - 179% (claim is 14% to 150%) |
| Analytical Specificity (Interference) | Insensitivity to listed substances | Insensitive to various substances (Hemoglobin, Triglyceride, Bilirubin, α2-Macroglobulin, α1-antitrypsin, Unfractionated heparin, Low Molecular Weighted heparin, Bivariludin, Dabigatran, Argatroban, Rivaroxaban) |
| Precision (Coagpia Calibrator) | ||
| Repeatability (Within-Run) CV | ≤ 10% | 0.8% |
| Between-Run CV | ≤ 10% | 1.5% |
| Between-Day CV | ≤ 10% | 0.0% |
| Between-Lot CV | ≤ 10% | 2.3% |
| Within-Laboratory CV | ≤ 10% | 2.8% |
| Between Instrument CV | ≤ 15% | 1.5% |
| Total CV | ≤ 15% | 3.2% |
| Precision (Coagpia Control Set) | ||
| Repeatability (Within-Run) CV | <10% | Level 1: 0.9%; Level 2: 2.5% |
| Between-Run CV | <10% | Level 1: 1.4%; Level 2: 4.4% |
| Between-Day CV | <10% | Level 1: 0.3%; Level 2: 1.9% |
| Between-Lot CV | <10% | Level 1: 1.1%; Level 2: 2.8% |
| Within-Laboratory CV | <10% | Level 1: 2.1%; Level 2: 6.0% |
| Between Instrument CV | <15% | Level 1: 1.5%; Level 2: 3.5% |
| Total CV | <15% | Level 1: 2.6%; Level 2: 6.9% |
| Method Comparison | ||
| Slope (vs. predicate) | 0.90 to 1.10 | 1.012 |
| Correlation Coefficient (r) | ≥ 0.90 | 0.9909 |
| Reproducibility (Coagpia AT Reagent) | ||
| Repeatability (Within-Run) %CV | ≤ 10% (for all 6 levels) | 0.8% to 3.8% (for all 6 levels) |
| Total Reproducibility %CV | ≤ 15% (for all 6 levels) | 1.1% to 7.5% (for all 6 levels) |
| Reproducibility (Coagpia Control Set & Calibrator) | ||
| Repeatability (Within-Run) %CV | ≤ 10% | 0.8% to 3.2% |
| Total Reproducibility %CV | ≤ 15% | 2.7% to 6.1% |
2. Sample Size Used for the Test Set and Data Provenance
-
Precision (Coagpia AT Reagent, Calibrator, Control Set):
- Sample Size: Six samples (for Reagent precision), three lots of Calibrator, three lots of Control Set. Each tested in duplicate, twice per day, for 20 non-consecutive days, on three CP3000 analyzers.
- Data Provenance: Not explicitly stated, but clinical laboratory settings are mentioned ("trained laboratory personnel in clinical laboratories"). Given it's a submission for US market through FDA, it likely includes data relevant to a US or internationally recognized clinical setting. It's prospective data collection given the structured study design (20 non-consecutive days).
-
Analytical Sensitivity (LOQ, LOB, LOD):
- Sample Size: Five natural plasmas (for LOQ, LOB, LOD), five analyte-free plasmas (for LOB, LOD). Measured in quadruplicate using three lots of Coagpia AT Reagent on two CP3000 analyzers. Measurement conducted for four days (total of 80 replicates per analyzer for LOQ).
- Data Provenance: Not explicitly stated. This is internal analytical validation data, likely from the manufacturer's lab. Prospective.
-
Linearity:
- Sample Size: High AT plasma diluted with AT deficient plasma to create a series of concentrations. Each sample measured in quadruplicate using three lots of Coagpia AT Reagent.
- Data Provenance: Not explicitly stated. Internal analytical validation data. Prospective.
-
Clinical Reportable Range (CRR):
- Sample Size: High AT plasma diluted with AT deficient plasma to create sample concentrations. Each sample measured in quadruplicate using three lots of Coagpia AT Reagent.
- Data Provenance: Not explicitly stated. Internal analytical validation data. Prospective.
-
Analytical Specificity (Interference):
- Sample Size: Not explicitly detailed, but involved testing sensitivity to various interfering substances.
- Data Provenance: Not explicitly stated. Internal analytical validation data. Prospective.
-
Method Comparison:
- Sample Size: 482 samples.
- Data Provenance: Left-over, prospectively collected, citrated plasma samples. Conducted at three (3) external sites. Country of origin not specified, but likely US given the FDA submission. Prospective.
-
Normal Reference Range:
- Sample Size: 179 samples.
- Data Provenance: Fresh citrated plasma samples collected from consented, apparently healthy adult volunteers. Conducted at three (3) external sites. Country of origin not specified, but likely US. Prospective.
-
Reproducibility (Coagpia AT Reagent, Calibrator, Control Set):
- Sample Size: Six levels (for Coagpia AT Reagent), Control Level 1, Control Level 2, and Calibrator (for Control Set and Calibrator). Each level had N=270 (implying 5 days x 2 runs/day x 3 replicates/run x 3 sites = 90 tests per site * 3 sites = 270 replicates).
- Data Provenance: Not explicitly stated, but conducted at three (3) external sites. Prospective.
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" or "ground truth" in the context of human interpretation or review of the test results for this
In-vitro Diagnostic (IVD) device. The ground truth for this type of device is typically established through:
- Reference Methods: Comparison against established, legally marketed predicate devices, considered the standard for measuring AT activity.
- Known Concentrations: Use of spiked samples, diluted samples, or reference materials with known concentrations of the analyte.
- Clinical Studies: Determining normal reference ranges based on samples from healthy individuals.
The method comparison study used the predicate device (HemosIL Liquid Antithrombin on ACL TOP 700 System) as the reference for comparison, which implicitly serves as the "ground truth" for evaluating the new device's accuracy.
4. Adjudication Method for the Test Set
Not applicable. As described above, there's no mention of human adjudication of results in the context of this IVD device. The evaluations are based on quantitative measurements and statistical analysis against defined criteria and predicate device performance.
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 is an In-Vitro Diagnostic (IVD) device (coagulation analyzer and reagents), not an AI-assisted diagnostic imaging or interpretation system that would involve human "readers" or "AI assistance" in the typical sense of MRMC studies.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are standalone performance studies of the device (CP3000 analyzer and Coagpia AT Reagent, Calibrator, Control Set). The device generates quantitative results (Antithrombin activity) automatically, without direct human intervention in the measurement process or interpretation beyond standard lab practices for running assays and reporting results. The device's performance is assessed based on its ability to accurately and precisely determine AT activity.
7. The Type of Ground Truth Used
The ground truth for the analytical and clinical studies varied:
- Method Comparison: The predicate device (HemosIL Liquid Antithrombin on ACL TOP 700 System) served as the de facto "ground truth" or reference standard against which the new device's measurements were compared.
- Precision, Analytical Sensitivity, Linearity, CRR, Analytical Specificity: Ground truth was established through known concentrations (e.g., highly concentrated plasma diluted with AT deficient plasma), calibrated reference standards, and defined acceptable ranges based on scientific principles and regulatory guidance (e.g., CLSI standards).
- Normal Reference Range: Ground truth was derived from samples collected from "apparently healthy adult volunteers," establishing a statistically derived normal range for the population.
8. The Sample Size for the Training Set
No specific "training set" is mentioned in the context of machine learning. This is a traditional IVD device, not an AI/ML-based device that typically undergoes a distinct training phase with a dedicated dataset. The development and optimization of the analyzer and reagents would involve internal development and validation data, but this is not typically referred to as a "training set" in the context of regulatory submissions.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no mention of a "training set" in the context of an AI/ML device.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.
May 9, 2018
Sekisui Medical Co., Ltd. % Shelly Harris Director of Regulatory Affairs Sekisui Diagnostics, LLC 6659 Top Gun Drive San Diego, California 92121
Re: K173202
Trade/Device Name: CP3000 Coagulation analyzer, Coagpia AT Reagent, Coagpia Calibrator, Coagpia Control Set Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: JPA, JBQ, JIX, GGN Dated: March 23, 2018 Received: April 9, 2018
Dear Shelly Harris:
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. 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 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
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173202
Device Name
CP3000 Coagulation Analyzer, Coagpia AT Reagent, Coagpia Calibrator, and Coagpia Control Set
Indications for Use (Describe)
CP3000 analyzer
The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays.
Coagpia AT Reagent
Coagpia AT Reagent is intended for the quantitative determination (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use.
Coagpia Calibrator
The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. - Coagpia AT Reagent
Coagpia Control Set
The Coagpia Control Set contains 2 levels of assaved plasma intended for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. - Coagpia AT Reagent
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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SECTION 5 510(K) SUMMARY
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR §807.92. This is a Traditional 510(k).
SPONSOR/APPLICANT INFORMATION AND DATE [807.92(A) (1)] 5.1.
| Owner/Manufacturer Name and Address: | Sekisui Medical Co., Ltd.1-3, Nihonbashi, 2-ChomeChuo-ku, Tokyo 103-0027, JapanFEI Number: 3006769061Establishment Registration Number: 3003539867 |
|---|---|
| Submitter Name and Address: | Sekisui Medical Co., Ltd.1-3, Nihonbashi, 2-ChomeChuo-ku, Tokyo 103-0027, JapanFEI Number: 3006769061Establishment Registration Number: 3003539867 |
| Contact Person: | Shelly HarrisDirector of Regulatory AffairsSekisui Diagnostics, LLC(858) 777-2627Michelle.harris@sekisui-dx.com |
| Application correspondent: | Shelly HarrisDirector of Regulatory AffairsSekisui Diagnostics, LLC(858) 777-2627Michelle.harris@sekisui-dx.com |
Date Summary prepared:
May 3, 2018
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| Trade Name | Common Name | Classification Name | Classification | Product |
|---|---|---|---|---|
| Code | ||||
| CP3000 | Coagulation | Multipurpose system for in | Class II | JPA |
| Analyzers | vitro coagulation studies | 21 CFR 864.5425 | ||
| Coagpia AT | Antithrombin | Antithrombin III assay | Class II | JBO |
| Reagent | assay reagent | 21 CFR 864.7060 | ||
| Coagpia Calibrator | Calibrator | Calibrator, multi-analyte | Class II | JIX |
| (Standard | mixture | 21 CFR 864.5425 | ||
| Human Plasma) | ||||
| Coagpia Control | Plasma, Coagulation | Class II | GGN | |
| Set | Control Plasma | Control | 21 CFR 864.5425 |
5.2. DEVICE NAME AND CLASSIFICATION [807.92 (A)(2)]
5.3. IDENTIFICATION OF LEGALLY MARKETED PREDICATE DEVICES [807.92(A)(3)]
| Trade Name | Predicate Device | Predicate 510(k) Number |
|---|---|---|
| CP3000 | ACL TOP | K160276- ACL TOP 700 LAS |
| Coagpia AT Reagent | HemosIL Liquid Antithrombin | K062431 |
| Coagpia Calibrator | HemosIL Calibration Plasma | K041905 |
| Coagpia Control Set | HemosIL Normal Control AssayedHemosIL Low Abnormal Control Assayed | K021023K021024 |
5.4. DEVICE DESCRIPTION [807.92 (A)(4)]
| 5.4.DEVICE DESCRIPTION 807.92 (A)(4) | |
|---|---|
| Trade Name | Device Description |
| CP3000 | The CP3000 is designed for easy-to-use, rapid in-vitro blood coagulation testing |
| on citrated human plasma. The CP3000 system is capable of performing the | |
| chromogenic methodologic assay, giving the user the ability to perform analysis | |
| for both direct hemostasis measurements and calculated parameters. For these | |
| assay methodologies, the analyzers employs two photometric detection methods: | |
| light scattering and absorbance. The light scattering method uses light emitting | |
| diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp | |
| with filters providing wavelengths at 405/570/730 nm. | |
| Coagpia AT | Coagpia AT Reagent is intended for the quantitative determination of antithrombin |
| Reagent | (AT) activity in human plasma on the CP3000 analyzers. The reagent is supplied |
| in a kit of 2 x 10 mL of Reagent 1 and 1 x 10mL of Reagent 2. Both reagents are | |
| liquid and do not require any preparation prior to use. | |
| Coagpia | The Coagpia Calibrator is supplied as 10 vials of lyophilized human plasma and is |
| Calibrator | suitable for the calibration of the antithrombin activity assay using Coagpia AT |
| Reagent on the CP3000 coagulation analyzers. |
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| Trade Name | Device Description |
|---|---|
| Coagpia ControlSet | The Coagpia Control Set is supplied as10 vials of lyophilized human plasma; 5 vials of Level 1 Control and 5 vials of Level 2 Control and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzers. |
| Trade Name | Intended Use | |
|---|---|---|
| CP3000 | The CP3000 is a fully automated, random-access in vitro blood coagulation | |
| analyzer intended for use by healthcare professionals in the clinical | ||
| laboratory. The CP3000 analyzer is designed to process plasma samples | ||
| photometrically using chromogenic assays. | ||
| Coagpia AT Reagent | Coagpia AT Reagent is intended for the quantitative determination of | |
| antithrombin (AT) activity in human 3.2% citrated venous plasma. The | ||
| reagent is intended for use on Sekisui CP3000 analyzers by trained | ||
| laboratory personnel in clinical laboratories. For in vitro diagnostic use. | ||
| Coagpia Calibrator | The Coagpia Calibrator is intended for use as a calibration plasma for the | |
| following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained | ||
| laboratory personnel in clinical laboratories. For in vitro diagnostic use. | ||
| Coagpia AT Reagent | ||
| Coagpia Control Set | The Coagpia Control set contains 2 levels of assayed plasma intended for the | |
| quality control of the following Sekisui coagulation assay on Sekisui CP3000 | ||
| analyzers by trained laboratory personnel. For in vitro diagnostic use. | ||
| Coagpia AT Reagent |
INTENDED USE [807.92 (A)(5)] 5.5.
TECHNOLOGICAL SIMILARITIES AND DIFFERENCES TO THE PREDICATE 5.6. [807.92 (A)(6)]
The CP3000 coagulation analyzers and Coagpia AT Reagent, Coagpia Calibrator and Coagpia Control Set included in the submission each has a unique predicate device, as described in the tables below.
5.6.1 CP3000 Coagulation Analyzers
| Characteristic | New Device | Predicate Device |
|---|---|---|
| ---------------- | ------------ | ------------------ |
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| CP3000 (CTS and non-CTS)(There will be 2 catalog codes forCTS and non-CTS)(Proposed) | ACL TOP 700 (CTS and non-CTS)(K160276) | |
|---|---|---|
| Options | Available with closed tube sampling(CTS) function | Same |
| Analytes | Multiple | Same |
| Intended Use andIndications for Use | The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. | 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 measurement and calculated parameter. |
| Method Types | Chromogenic | Coagulometric (turbidimetric) measurement Chromogenic (absorbance) measurement Immunological measurement |
| Interface | Touch screen operation Windows 7 Operating System | Touch screen operation Windows XP Operating System |
| Detection | Photometric Absorbance Light scattering | Photometric Absorbance |
| Wavelengths | 405 nm 570 nm 660 nm 730 nm | 405 nm 671 nm |
| Throughput(non-CTS) | Up to 400 clotting tests/hour | Up to 330 PT and APTT tests/hour |
| Reagent Handling | Refrigerated on board Internal bar code sample identification | Same |
|---|---|---|
| ------------------ | --------------------------------------------------------------- | ------ |
5.6.2 Coagpia AT Reagent
| Characteristic | New Device | Predicate Device |
|---|---|---|
| Coagpia AT Reagent(Proposed) | HemosIL Liquid Antithrombin(K062431) | |
| Analyte | Antithrombin | Same |
| Indications for Use | Coagpia AT Reagent is intended for thequantitative determination ofantithrombin (AT) activity in human3.2% citrated venous plasma. Thereagent is intended for use on SekisuiCP3000 analyzers by trained laboratorypersonnel in clinical laboratories. For invitro diagnostic use. | HemosIL Liquid Antithrombin is anautomated chromogenic assay for thequantitative determination ofAntithrombin in human citrated plasmaas an aid in the diagnosis of hereditaryand acquired Antithrombin deficiencyand to monitor Antithrombinsubstitution therapy.This in vitro diagnostic test is based ona synthetic chromogenic substrate andon Factor Xa inactivation. As aconsequence, it is specific and notinfluenced by Heparin Cofactor II.Antithrombin levels in patient plasmaare measured automatically on ILCoagulation Systems. |
| Reagent State | Liquid, ready to use | Same |
| Method | Chromogenic | Same |
| Detection | Photometric | Same |
| Key Components | Factor Xa (bovine) Heparin N-Acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilidedihydrochloride (chromogenicsubstrate) | Factor Xa (bovine) Heparin N-α-Z-D-Arg-Gly-Arg-pNA·2HCl (chromogenicsubstrate) |
| Sample Type | Human citrated plasma | Human citrated plasma |
| Expected Values | 89 - 131% | 83 - 128% |
| Repeatability | 0.7-2.9% | 2.2 - 7.4% |
| Within Laboratory | 1.1-5.8% | 3.1 - 8.6% |
| Characteristic | New Device | Predicate Device |
| Coagpia AT Reagent(Proposed) | HemosIL Liquid Antithrombin(K062431) | |
| Precision | ||
| Clinical ReportableRange (CRR) | 14-150% | 10 - 150% |
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5.6.3 Coagpia Calibrator
| Characteristic | New Device | Predicate Device |
|---|---|---|
| Coagpia Calibrator (Proposed) | HemosIL Calibration plasma (K041905) | |
| Intended Use andIndications for Use | The Coagpia Calibrator is intended foruse as a calibration plasma for thefollowing Sekisui coagulation assay onSekisui CP3000 analyzers by trainedlaboratory personnel in clinicallaboratories. For in vitro diagnosticuse.Coagpia AT Reagent | HemosIL Calibration plasma is intendedfor the calibration of coagulation assays onIL and ELECTRA Coagulation Systems.Used for the determination of PT,Fibrinogen, Single Factors, von WillebrandFactor, Antithrombin, Plasminogen,Plasmin Inhibitor, Protein C, Protein S, andas a reference plasma for APTT and TT. |
| Format | Lyophilized | Same |
| Calibrator Type | Antithrombin | Fibrinogen, Antithrombin, PT, SingleFactors, von Willebrand Factor,Plasminogen, Plasmin Inhibitor, Protein C,Protein S, and as a reference plasma forAPTT and TT. |
| Key Components | Human plasma | Same |
5.6.4 Coagpia Control Set
| New Device | Predicate Device | ||
|---|---|---|---|
| Characteristic | Coagpia Control Set(Proposed) | HemosIL NormalControl Assayed(K021023) | HemosIL High AbnormalControl Assayed(K021024) |
| Intended Use andIndications forUse | The Coagpia Control setcontains 2 levels of assayedplasma intended for the qualitycontrol of the followingSekisui coagulation assay onSekisui CP3000 analyzers bytrained laboratory personnel.For in vitro diagnostic use.• Coagpia AT Reagent | HemosIL NormalControl ASSAYED isintended for the qualitycontrol of coagulationassays in the normalrange on IL Coagulationand ELECTRA Systems.The normal control isprepared using humancitrated plasma fromHealth donors. Valuesfor all analytes are | HemosIL High AbnormalControl ASSAYED isintended for the qualitycontrol of coagulation assaysin the high abnormal rangeon IL Coagulation andELECTRA Systems. TheHigh Abnormal Control isprepared using humancitrated plasma from healthydonors (not heparinizedplasma or plasma samplesunder oral anticoagulation |
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| within the normal range. therapy) and modified tostimulate an abnormalcoagulation sample. Valuesfor all analytes are in thehigh abnormal range. | |||
|---|---|---|---|
| Format | Lyophilized | Same | Same |
| Key Components | Human plasma | Same | Same |
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5.7. SUMMARY OF NON-CLINICAL PERFORMANCE DATA [807.92 (B)(1)] 5.7.1 CP3000 Coagulation analyzers
The CP3000 analyzers were successfully tested for electrical safety, emissions and immunity according to the following standards:
| Description | Standard | Title |
|---|---|---|
| ElectricalSafetyTesting | IEC 61010-1 | Safety requirements for electrical equipment formeasurement, control and laboratory use. Part 1: Generalrequirements |
| IEC 61010-2-081 | Safety requirements for electrical equipment formeasurement, control and laboratory use – Part 2-081:Particular requirements for automatic and semi-automaticlaboratory equipment for analysis and other purposes | |
| IEC 60825-1 | Safety of laser products – Part 1: Equipment classificationand requirements | |
| IEC61010-2-101 | Safety requirements for electrical equipment formeasurement, control and laboratory use – Part 2-101.Particular requirements for in vitro diagnostic (IVD)medical equipment | |
| Emission | IEC 61326-2-6 | Electrical equipment for measurement, control andlaboratory use – EMC requirements – Part 2-6: Particularrequirements – In vitro diagnostic (IVD) medicalequipment |
| CISPR 11 | Industrial, scientific and medical equipment – Radio-frequency disturbance characteristics – Limits and methodsof measurement | |
| IEC 61000-3-2 | Electromagnetic compatibility (EMC) – Part 3-2: Limits –Limits for harmonic current emissions | |
| IEC 61000-3-3 | Electromagnetic compatibility (EMC) – Part 3-3: Limits –Limitation of voltage changes, voltage fluctuations andflicker in public low – voltage supply systems, forequipment with rated current ≤16 A per phase and not | |
| Description | Standard | Title |
| subject to conditional connection | ||
| Immunity | IEC 61326-2-6 | Electrical equipment for measurement, control andlaboratory use – EMC requirements – Part 2-6: Particularrequirements – In vitro diagnostic (ICD) medical equipment |
| IEC 61000-4-2 | Electromagnetic compatibility (EMC) – Part 4-2: Testingand measurement techniques – Electrostatic dischargeimmunity test | |
| IEC 61000-4-3 | Electromagnetic compatibility (EMC) – Part 4-3: Testingand measurement techniques - Radiated, radio-frequency,electromagnetic field immunity test | |
| IEC 61000-4-4 | Electromagnetic compatibility (EMC) – Part 4-4: Testingand measurement techniques – Electrical fast transient/burstimmunity test | |
| IEC 61000-4-5 | Electromagnetic compatibility (EMC) – Part 4-5: Testingand measurement techniques – Surge immunity test | |
| IEC 61000-4-6 | Electromagnetic compatibility (EMC) – Part 4-6: Testingand measurement techniques - Immunity to conducteddisturbances, induced by radio-frequency fields | |
| IEC 61000-4-8 | Electromagnetic compatibility (EMC) – Part 4-8: Testingand measurement techniques - Power frequency magneticfield immunity test | |
| IEC 61000-4-11 | Electromagnetic compatibility (EMC) – Part 4-11: Testingand measurement techniques – Voltage dips, shortinterruptions and voltage variations immunity tests |
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5.7.2 Coagpia AT Reagent
Precision
Precision studies were performed according to CLSI EP5-A3. Repeatability (Within-Run precision), Between-Run precision, Between-day precision, Between Instrument, and Total precision were determined using six samples tested in duplicate, twice per day on 20 non-consecutive days on three CP3000 analyzers using three lots of Coagpia AT Reagent. The following results were demonstrated:
| Sample | Mean | Repeatability | Between Run | Between Day | Between Lot | WithinLaboratory | BetweenInstrument | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | ||
| Sample 1 | 31.1 | 0.9 | 2.9% | 1.6 | 5.1% | 0.0 | 0.0% | 0.3 | 1.0% | 1.8 | 5.8% | 1.5 | 4.8% | 2.4 | 7.7% |
| Sample 2 | 54.6 | 0.9 | 1.6% | 1.4 | 2.6% | 0.2 | 0.4% | 0.2 | 0.4% | 1.7 | 3.1% | 1.5 | 2.7% | 2.3 | 4.2% |
| Sample 3 | 79.9 | 0.8 | 1.0% | 1.4 | 1.8% | 0.0 | 0.0% | 0.3 | 0.4% | 1.6 | 2.0% | 1.1 | 1.4% | 2.0 | 2.5% |
| Sample 4 | 106.5 | 1.0 | 0.9% | 1.3 | 1.2% | 0.0 | 0.0% | 0.5 | 0.5% | 1.7 | 1.6% | 1.1 | 1.0% | 2.1 | 2.0% |
| Sample 5 | 130.8 | 0.9 | 0.7% | 1.1 | 0.8% | 0.1 | 0.1% | 0.5 | 0.4% | 1.5 | 1.1% | 0.8 | 0.6% | 1.7 | 1.3% |
| Sample 6 | 151.2 | 3.2 | 2.1% | 2.8 | 1.9% | 0.0 | 0.0% | 0.5 | 0.3% | 4.3 | 2.8% | 2.8 | 1.9% | 5.1 | 3.4% |
| Criteria | $ \le 10% $ | $ \le 10% $ | $ \le 10% $ | $ \le 10% $ | $ \le 10% $ | $ \le 15% $ | $ \le 15% $ | ||||||||
| Pass/Fail | Pass | Pass | Pass | Pass | Pass | Pass | Pass |
Analytical Sensitivity
Limit of Quantitation:
Limit of Quantitation (LOQ) represents the lowest amount of AT that can be detected reliably. Five natural plasmas at concentrations near the lower limit of Reportable Range were measured in quadruplicate using three lots of Coagpia AT Reagent on two CP3000 analyzers. Measurement has been conducted for four days for a total of eighty replicates per analyzer (5 samples x quadruplicate x 4 days). LOQ was determined at the level where the calculated total error estimate falls within the defined goal (total error ≤15%). The Limit of Quantitation was determined to be 11%.
Limit of Blank:
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Limit of blank (LOB) is the highest concentration likely to be measured for a blank sample. Five analyte-free plasmas and five natural plasmas at concentrations near the lower limit of Reportable Range were measured in quadruplicate using three lots of Coagpia AT Reagent on two CP3000 analyzers. Results were processed and analyzed following CLSI Guidance EP17-A. The Limit of blank was determined to be 3%.
Limit of Detection:
Limit of detection (LOD) is the lowest concentration of an analyte that is reliably detected. Five analyte-free plasmas and five natural plasmas at concentrations near the lower limit of Reportable Range were measured in quadruplicate using three lots of Coagpia AT Reagent on two CP3000 analyzers. Results were processed and analyzed following CLSI Guidance EP17-A. The Limit of Detection was determined to be 5%.
Linearity:
High AT plasma (pooled plasma) was diluted with AT deficient plasma to create the sample concentration required for this evaluation. The dilution series was prepared above and below the anticipated linear range of the test method as recommended by CLSI EP6-A. Each sample was measured in quadruplicate using three lots of Coagpia AT Reagent. Linearity range was determined at the calculated allowable non linearity estimate falls within the defined goal (allowable non linearity <20%). The data demonstrate a Linear Range of 14 - 140%.
Clinical Reportable Range:
A clinical reportable range study was conducted to determine the upper limit of the measurable range of the assay. The Auto Dilution (auto-rerun as defined in the system software) function was turned on for this study. High AT plasma (pooled plasma) was diluted with AT deficient plasma to create the sample concentration required for this evaluation. Each sample was measured in quadruplicate using three lots of Coagpia AT Reagent. % Difference (Recovery) to the theoretical value has been calculated for each measurement result. Measurement range of which % difference falls within =10% has been determined. The data demonstrate measurement range up to 179% which met the design goal of 150%. The following Table summarizes the Analytical Data.
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| Analytical Data Summary | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| AT Lot # | LOQ | LOB | LOD | Lower limit of LinearRange | Upper limit of ReportableRange | |||||
| IUO001 | 11% | 3% | 4-5% | 10.8 % | 182% | |||||
| IUO002 | 11% | 2% | 4% | 14.0 % | 179% | |||||
| IUO003 | 11% | 3% | 4-5% | 11.0 % | 182% |
Based on this result, the Clinical Reportable Range (CRR) of the Coagpia AT Reagent on CP3000 analyzers have been verified from 14% to 179%. The CRR claim is 14% to 150%.
Analytical Specificity (Endogenous and Exogenous Interference)
Interference studies were performed according to the paired difference method reference in CLSI EP7A2. The Coagpia AT Reagent is insensitive to the following substances:
- . Hemoglobin concentration up to 700mg/dL
- . Triglyceride concentration up to 2000mg/dL
- . Unconjugated Bilirubin concentration up to 100mg/dL
- Conjugated Bilirubin concentration up to 100mg/dL
- α2-Macroglobulin concentration up to 500mg/dL ●
- α1-antitrypsin concentration up to 600mg/dL ●
- Unfractionated heparin concentration up to 8.0IU/mL ●
- . Low Molecular Weighted heparin concentration up to 8.0IU/mL
- Bivariludin concentration of to 30μg/mL .
- Dabigatran concentration up to 1000ng/mL ●
- Argatroban concentration up to 2500ng/mL .
- Rivaroxaban concentration up to 25ng/mL .
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5.7.3 Coagpia Calibrator
Precision
Precision studies were performed according to CLSI EP5-A3. Repeatability (Within-Run precision), Between-Run precision, Between-day precision, Between-lot precision, Within-laboratory precision, and Total precision were determined using three lots of Coagpia Calibrator tested in in duplicate, twice per day on 20 nonconsecutive days on three CP3000 analyzers using three lots of Coagpia AT Reagent calibrated with in-house primary reference standard. The following result were demonstrated:
| Mean | Within Run | Between Run | Between Day | Between Lot | WithinLaboratory | BetweenInstrument | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV | SD | CV | SD | SD | SD | CV | SD | CV | SD | CV | SD | CV | |
| 103.1 | 0.8 | 0.8% | 1.5 | 1.5% | 0.0 | 0.0% | 2.4 | 2.3% | 2.9 | 2.8% | 1.5 | 1.5% | 3.3 | 3.2% |
| Criteria | ≤10% | ≤10% | ≤10% | ≤10% | ≤10% | ≤15% | ≤15% | |||||||
| Pass/Fail | Pass | Pass | Pass | Pass | Pass | Pass | Pass |
5.7.4 Coagpia Control Set
Precision
Precision studies were performed according to CLSI EPS-A3. Repeatability (Within-Run precision), Between-Run precision, Between-day precision, Between-lot precision, Within-laboratory precision, and Total precision were determined using three lots of Coagpia Control Set tested in in duplicate, twice per day on 20 nonconsecutive days on three CP3000 analyzers using three lots of Coagpia AT Reagent calibrated with in-house primary reference standard. The following result were demonstrated:
| CoagpiaControlSet | Mean | Within Run | Between Run | Between Day | Between Lot | Within Laboratory | BetweenInstrument | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | ||
| Level 1 | 99.5 | 0.9 | 0.9% | 1.4 | 1.4% | 0.3 | 0.3% | 1.1 | 1.1% | 2.1 | 2.1% | ો રે | 1.5% | 2.6 | 2.6% |
| Level 2 | 31.8 | 0.8 | 2.5% | 1.4 | 4.4% | 0.6 | 1.9% | 0.9 | 2.8% | 1.9 | 6.0% | 1.1 | 3.5% | 2.2 | 6.9% |
| Criteria | <10% | <10% | <10% | <10% | <10% | <15% | <15% | ||||||||
| Pass/Fail | Pass | Pass | Pass | Pass | Pass | Pass | Pass |
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SUMMARY OF CLINICAL PERFORMANCE CHARACTERISTICS 5.8.
Method comparison with predicate device:
A method comparison study was performed to compare the performance of the CP3000 with Coagpia AT Reagent to the predicate device, Instrumentation Laboratories (IL) ACL TOP 700 with HemosIL Liquid Antithrombin. The study was conducted at three (3) externals sites utilizing left-over, prospectively collected, citrated plasma samples. A total of 482 samples were analyzed. Results were analyzed using Deming regression. All results met the acceptance criteria: Slope 0.90 to 1.10; Correlation Coefficient (r) ≥ 0.90. The following table summarizes the regression results:
| Instrument | Slope | Intercept | |||
|---|---|---|---|---|---|
| CP3000 | 482 | 1.012 | U.T | 0.9909 |
Normal reference range:
A normal reference interval study was conducted to determine the normal reference range for the Coagpia AT assay. The study was conducted at three (3) external sites utilizing fresh citrated plasma samples collected from consented, apparently healthy adult volunteers. A total of 179 samples were analyzed. The reference range was established by calculating the non-parametric 95% confidence interval (2.5th to 97.5th percentiles). The mean of the reference range was 108.9% and the central 95% range was 89% to 131%. The following table summarizes the results for the normal reference interval:
| Reference Interval | Lower Limit | Upper Limit |
|---|---|---|
| Antithrombin | 89% | 131% |
Reproducibility:
The reproducibility study utilized a 5x2x3x3 design (five non-consecutive days, two runs per day, three replicates per run at three sites). Three lots of Coagpia AT Reagent were evaluated for repeatability (within-run) and total reproducibility. The mean, SD and %CV were calculated for each sample tested. For repeatability, the %CV for all six levels ranged from 0.8% to 3.8% which met the acceptance criteria of ≤ 10%. For total reproducibility, the %CV for all six levels ranged from 1.1% to 7.5% which met the acceptance criteria of ≤ 15%. The following table summarizes the reproducibility results for the Coagpia AT Reagent for all sites combined:
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| Within-Run | Total | |||||
|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV |
| Level 1 | 270 | 30.0 | ાં 15 | 3.8% | 2.26 | 7.5% |
| Level 2 | 270 | 51.7 | 1.00 | 1.9% | 2.02 | 3.9% |
| Level 3 | 270 | 77.5 | 0.86 | 1.1% | 1.45 | 1.9% |
| Level 4 | 270 | 102.8 | 0.98 | 1.0% | 1.43 | 1.4% |
| Level 5 | 270 | 122.7 | 1.03 | 0.8% | 1.36 | 1.1% |
| Level 6 | 270 | 145.3 | 2.01 | 1.4% | 3.06 | 2.1% |
Three lots of Coagpia Control Set and three lots of Coagpia Calibrator were evaluated for repeatability (within-run) and total reproducibility. The mean, SD and %CV were calculated for each sample tested. For repeatability, the %CV ranged from 0.8% to 3.2% which met the acceptance criteria of ≤ 10%. For total reproducibility, the %CV ranged from 2.7% to 6.1% which met the acceptance criteria of ≤ 15%. The following table summarizes the reproducibility results for the Coagpia Control Set and Coagpia Calibrator for all sites combined:
| Within-Run | Total | |||||
|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV |
| Control Level 1 | 270 | 99.4 | 0.84 | 0.8% | 2.70 | 2.7% |
| Control Level 2 | 270 | 33.3 | 1.08 | 3.2% | 2.03 | 6.1% |
| Calibrator | 270 | 102.2 | 1.00 | 1.0% | 3.07 | 3.0% |
5.9. CONCLUSION
Coagpia AT Reagent on CP3000 analyzers system was shown to be substantially equivalent to the HemosIL liquid Antithrombin assay (K062431) on ACL TOP700 System (K160276).
§ 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.