(130 days)
The intended use of the Sysmex® CA-500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform coagulation tests.
The Sysmex® CA-500 series is a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The manufacturer has modified the series to include two new models with immunological testing capability. The proposed Sysmex CA-500 series can now provide accurate and precise test results for up to five parameters simultaneously and in random access. The CA-500 uses clot, chromogenic and immunological detection technologies for determination of the various parameters.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance:
The document presents two types of performance data: method comparison studies (comparing the CA-500 to predicate devices) and precision studies (evaluating the CA-500's internal consistency). The "acceptance criteria" are implied by the results needing to demonstrate substantial equivalence and acceptable precision for in vitro diagnostic use. Specific quantitative criteria are provided for the precision study.
| Test / Metric | Acceptance Criteria (Implied for Method Comparison, Explicit for Precision) | Reported Device Performance (CA-500) |
|---|---|---|
| Method Comparison Studies (vs. CA-7000 or CA-6000 Predicate Devices) | High Coefficient of Correlation (r) and linear regression close to Y=X (slope ~1, intercept ~0) for substantial equivalence. | D-Dimer Assay (Advanced D-Dimer): r=0.992, Y = 1.01X + 0.14PT, seconds (Thromborel® S): r=0.999, Y = 1.00X - 0.50PT, INR (Thromborel® S): r=0.999, Y = 0.89X + 0.11Derived Fibrinogen (Thromborel® S): r=0.998, Y = 1.08X + 0.04PT, seconds (Innovin®): r=0.999, Y = 1.03X - 0.26PT, INR (Innovin®): r=0.999, Y = 1.08X - 0.09Derived Fibrinogen (Innovin®): r=0.995, Y = 1.09X - 0.17PT, seconds (Thromboplastin C Plus): r=0.997, Y = 1.00X - 0.20PT, INR (Thromboplastin C Plus): r=0.998, Y = 1.00X - 0.00Derived Fibrinogen (Thromboplastin C Plus): r=0.998, Y = 1.12X + 0.03APTT (Actin®): r=0.982, Y = 1.00X - 0.20APTT (Actin® FS): r=0.983, Y = 1.00X + 0.10APTT (Actin® FSL): r=0.990, Y = 1.00X + 0.10All R-values are very close to 1, and regression equations show slopes generally close to 1 and intercepts close to 0, indicating strong correlation and agreement with the predicate devices. |
| Precision Studies (Total %CV) | Max. Error Criteria (%CV) specified for each assay/control level. | PT, Seconds (Thromborel® S): 0.9% and 1.5% (Max. 5% CV)PT, INR (Thromborel® S): 0.8% and 1.3% (Max. 5% CV)Derived Fibrinogen (Thromborel® S): 1.6% and 2.5% (Max. 10% CV)PT, Seconds (Innovin®): 0.4% and 1.8% (Max. 5% CV)PT, INR (Innovin®): 0.4% and 1.8% (Max. 5% CV)Derived Fibrinogen (Innovin®): 2.8% and 3.4% (Max. 10% CV)PT, Seconds (Thromboplastin C Plus): 0.4% and 1.8% (Max. 5% CV)PT, INR (Thromboplastin C Plus): 0.7% and 3.5% (Max. 5% CV)Derived Fibrinogen (Thromboplastin C Plus): 1.9% and 1.6% (Max. 10% CV)APTT (Dade® Actin): 3.5% and 1.4% (Max. 5% CV)APTT (Dade® Actin FS): 0.5% and 1.5% (Max. 5% CV)APTT (Dade® Actin® FSL): 0.4% and 1.5% (Max. 5% CV)D-Dimer (Advanced D-Dimer): 2.9% and 2.0% (Max. 15% CV)All reported Total %CV values are well within the specified maximum error criteria, indicating excellent precision. |
2. Sample size used for the test set and the data provenance:
- Test Set Sample Sizes:
- Method Comparison Studies:
- D-Dimer Assay: 390 samples
- PT (Thromborel® S): 248 samples
- Derived Fibrinogen (Thromborel® S): 248 samples
- PT (Innovin®): 243 samples
- Derived Fibrinogen (Innovin®): 247 samples
- PT (Thromboplastin C Plus): 245 samples
- Derived Fibrinogen (Thromboplastin C Plus): 245 samples
- APTT (Actin®): 864 samples
- APTT (Actin® FS): 857 samples
- APTT (Actin® FSL): 864 samples
- Precision Studies:
- For each assay and control level, 40 measurements (e.g., PT (Thromborel® S) at Control Plasma N: 40 measurements; PT (Thromborel® S) at Ci-Trol® Level 3: 40 measurements, etc.).
- Method Comparison Studies:
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It describes the samples as "citrated human plasma" and refers to "Control Plasma N" and "Path. Plasmapool" for validation, suggesting laboratory-obtained samples rather than patient-specific demographic data from a specific geographical location.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the document. For in vitro diagnostic devices like this coagulation analyzer, the "ground truth" is typically established by the reference methods performed on the predicate device or by established control materials with known values, not by independent expert interpretation in the same way it would be for imaging diagnostics. The study compares the new device's results to those of the predicate devices.
4. Adjudication method for the test set:
This information is not applicable for this type of device study. Adjudication methods (like 2+1, 3+1) are typically used in studies where human interpretation of data (e.g., medical images) is involved and discrepancies need to be resolved to establish ground truth. For an automated coagulation analyzer, the "ground truth" for method comparison is the measurement obtained from the predicate device, and for precision, it's the instrument's own internal consistency against known controls.
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:
This is not applicable to this device. The Sysmex® Automated Coagulation Analyzer CA-500 is an automated instrument, not an AI-assisted diagnostic tool that human readers use. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The performance presented for the Sysmex® Automated Coagulation Analyzer CA-500 is inherently standalone (algorithm/instrument only performance). As an automated analyzer, its primary function is to process samples and provide results without direct human interpretive intervention at the point of measurement. The studies quantify the agreement of its measurements with predicate devices and its internal precision.
7. The type of ground truth used:
The ground truth used for these studies is based on:
- Reference measurements from legally marketed predicate devices: For the method comparison studies, the results obtained from the Sysmex® Automated Coagulation Analyzer CA-7000 and CA-6000 (which are themselves established and cleared devices) served as the reference standard against which the CA-500's measurements were compared.
- Known values of control materials: For the precision studies, "Control Plasma N," "Ci-Trol® Level 3," "Path. Plasmapool," "Adv. D-D Control 1," and "Adv. D-D Control 2" were used. These are standard laboratory control materials with established reference ranges or target values that enable the assessment of an instrument's accuracy and precision.
8. The sample size for the training set:
This information is not provided and is generally not applicable in the context of traditional automated laboratory instruments. These instruments are typically developed and validated using engineering principles, analytical chemistry, and statistical methods rather than machine learning models that require distinct "training sets." The studies described are validation and performance testing, not model training.
9. How the ground truth for the training set was established:
As noted in point 8, the concept of a "training set" and "ground truth for the training set" as used in machine learning is not applicable to this device and its validation. The device's operational parameters and algorithms are designed and verified against established principles of coagulation testing and validated using control materials and comparison with predicate devices.
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Dade Behring Inc. 510(k) Premarket Notification Sysmex® Automated Coagulation Analyzer CA-500
510(k) Summary of Safety and Effectiveness Information Sysmex® Automated Coagulation Analyzer CA-500 April 30, 2003
MANUFACTURER AND CONTACT INFORMATION I.
| Contact Information: | Dade Behring Inc.P.O. Box 6101Newark, DE 19714-6101Attn: Radames RiesgoPhone: 305.480.7558FAX: 305.552.5288 | |
|---|---|---|
| Registration Number: | Manufacturing Site | |
| Sysmex Corporation | ||
| Kobe, Japan | 9613959 | |
| Importer | ||
| Sysmex Corporation of America | ||
| One Wildlife Way | ||
| Long Grove, IL 60047-9596 | 1422681 | |
| Distributor | ||
| Dade Behring Inc. | ||
| Glasgow Site | ||
| P.O. Box 6101 | ||
| Newark, DE 19714-6101 | 2517506 |
DEVICE NAME AND CLASSIFICATION NAME II.
Trade or Proprietary Name: Sysmex Automated Coagulation Analyzer CA-500
Common or Usual Name: Automated Coagulation System
Coagulation Instrument (21 CFR §864.5400) Classification Name:
III. IDENTIFICATION OF THE LEGALLY MARKETED DEVICE
Sysmex® Automated Coagulation Analyzer CA-7000 (K020979) Sysmex® Automated Coagulation Analyzer CA-6000 (K964139)
SEP - 8 2003
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DEVICE DESCRIPTION IV.
The Sysmex® CA-500 series is a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The manufacturer has modified the series to include two new models with immunological testing capability. The proposed Sysmex CA-500 series can now provide accurate and precise test results for up to five parameters simultaneously and in random access. The CA-500 uses clot, chromogenic and immunological detection technologies for determination of the various parameters.
DEVICE INTENDED USE V.
The intended use of the Sysmex® CA-500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories. The instrument uses citrated human plasma to perform coagulation tests.
VI. SUBSTANTIAL EQIVALENCE
The Sysmex® Automated Coagulation Analyzer CA-550 or CA-560 is substantially equivalent in intended use for D-Dimer testing to the Sysmex® Automated Coagulation Analyzer CA-7000, which was cleared under Document Control No. K020979.
The results of PT and APTT parameters using the new software version for the Sysmex® Automated Coagulation Analyzer CA-500 Series are substantially equivalent to the results for PT and APTT parameters obtained with the Sysmex® Automated Coagulation Analyzer CA-6000, which was cleared under Document Control No. K964139.
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VII. DEVICE PERFORMANCE CHARACTERISTICS
| Test | PredicateDevice | SampleNumber(n) | Coefficient ofCorrelation(r) | RegressionEquation |
|---|---|---|---|---|
| D-Dimer Assay(Advanced D-Dimer) | CA-7000 | 390 | 0.992 | Y = 1.01X + 0.14 |
| PT, seconds(Thromborel® S) | CA-6000 | 248 | 0.999 | Y = 1.00X - 0.50 |
| PT, INR(Thromborel® S) | CA-6000 | 248 | 0.999 | Y = 0.89X + 0.11 |
| Derived Fibrinogen(Thromborel® S) | CA-6000 | 248 | 0.998 | Y = 1.08X + 0.04 |
| PT, seconds(Innovin®) | CA-6000 | 243 | 0.999 | Y = 1.03X - 0.26 |
| PT, INR(Innovin®) | CA-6000 | 243 | 0.999 | Y = 1.08X - 0.09 |
| Derived Fibrinogen(Innovin®) | CA-6000 | 247 | 0.995 | Y = 1.09X - 0.17 |
| PT, seconds(Thromboplastin C Plus | CA-6000 | 245 | 0.997 | Y = 1.00X - 0.20 |
| PT, INR(Thromboplastin C Plus) | CA-6000 | 245 | 0.998 | Y = 1.00X - 0.00 |
| Derived Fibrinogen(Thromboplastin C Plus) | CA-6000 | 245 | 0.998 | Y = 1.12X + 0.03 |
| APTT(Actin®) | CA-6000 | 864 | 0.982 | Y = 1.00X - 0.20 |
| APTT(Actin® FS) | CA-6000 | 857 | 0.983 | Y = 1.00X + 0.10 |
| APTT(Actin® FSL) | CA-6000 | 864 | 0.990 | Y = 1.00X + 0.10 |
Summary of Method Comparison Studies between CA-500 and CA-7000 or CA-6000
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| Assay | Control Level | n | Mean | WithinRun%CV | BetweenRun%CV | Total%CV | Max.ErrorCriteria% CV |
|---|---|---|---|---|---|---|---|
| PT, Seconds(Thromborel® S) | Control Plasma NCi-Trol® Level 3 | 40 | 11.959.2 | 0.71.1 | 0.71.0 | 0.91.5 | 5 |
| PT, INR(Thromborel® S) | Control Plasma NCi-Trol® Level 3 | 40 | 1.14.6 | 0.61.0 | 0.60.9 | 0.81.3 | 5 |
| Derived Fibrinogen, g/L(Thromborel® S) | Control Plasma NPath. Plasmapool | 40 | 2.34.8 | 1.61.9 | 0.61.7 | 1.62.5 | 10 |
| PT, Seconds(Dade® Innovin®) | Control Plasma NCi-Trol® Level 3 | 40 | 11.538.0 | 0.40.9 | 0.21.5 | 0.41.8 | 5 |
| PT, INR(Dade® Innovin®) | Control Plasma NCi-Trol® Level 3 | 40 | 1.13.7 | 0.40.9 | 0.21.6 | 0.41.8 | 5 |
| Derived Fibrinogen, g/L(Dade® Innovin®) | Control Plasma NPath. Plasmapool | 40 | 1.95.2 | 2.63.2 | 1.41.6 | 2.83.4 | 10 |
| PT, Seconds(Thromboplastin C Plus) | Control Plasma NCi-Trol® Level 3 | 40 | 11.525.9 | 0.41.0 | 0.21.5 | 0.41.8 | 5 |
| PT, INR(Thromboplastin C Plus) | Control Plasma NCi-Trol® Level 3 | 40 | 1.05.0 | 0.71.9 | 0.43.0 | 0.73.5 | 5 |
| Derived Fibrinogen, g/L(Thromboplastin C Plus) | Control Plasma NPath. Plasmapool | 40 | 2.55.0 | 1.51.6 | 1.30.6 | 1.91.6 | 10 |
| APTT(Dade® Actin) | Control Plasma NCi-Trol® Level 3 | 40 | 26.857.9 | 1.00.6 | 3.41.3 | 3.51.4 | 5 |
| APTT(Dade® Actin FS) | Control Plasma NCi-Trol® Level 3 | 40 | 27.163.8 | 0.50.3 | 0.21.5 | 0.51.5 | 5 |
| APTT(Dade® Actin® FSL) | Control Plasma NCi-Trol® Level 3 | 40 | 29.361.4 | 0.40.4 | 0.21.4 | 0.41.5 | 5 |
| D-Dimer(Advanced D-Dimer) | Adv. D-D Control 1Adv. D-D Control 2 | 40 | 5.020.5 | 2.41.6 | 1.81.4 | 2.92.0 | 15 |
Summary of Precision Studies Sysmex® Automated Coagulation Analyzer CA-500
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three wing strokes, symbolizing the department's mission to protect and promote the health and well-being of all Americans. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle symbol.
SEP - 8 2003
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Radames Riesgo Manager, Regulatory Affairs & Compliance Dade Behring Inc. P.O. Box 6101 Newark, DE 19714
Re: K031377 Trade/Device Name: Sysmex® Automated Coagulation Analyzer CA-500 Regulation Number: 21 CFR 864.5400 Regulation Name: Coagulation instrument Regulatory Class: Class II Product Code: GKP Dated: August 7, 2003 Received: August 8, 2003
Dear Mr. Riesgo:
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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours.
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________
Device Name: Sysmex® Automated Coagulation Analyzer CA-500
Indications for Use:
The intended use of the Sysmex® CA-500 is as a fully automated, computerized blood plasma coagulation analyzer for in vitro diagnostic use in clinical laboratories.
The instrument uses citrated human plasma to perform coagulation tests.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Jourdine Bautista
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K0231377
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter-Use (Optional Format 1-2-96)
§ 864.5400 Coagulation instrument.
(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.