(63 days)
The Pacific Hemostasis ThromboScreen® 200 is a photo-optical instrument used for the performance of in-vitro diagnostic coagulation testing of citrated plasma specimens in the clinical laboratory. Coagulation testing capabilities of the device include routine clotting tests such as Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (Clauss and Derived methods), as well as PT and APTT-based factor assays.
The ThromboScreen® 200 (TS200) is a photo-optical instrument used for the performance of invitro diagnostic clotting procedures in the clinical laboratory. The instrument utilizes photo-optical principles to measure and record the time required for patient plasma specimens to clot. The ThromboScreen® 200 light source is provided by a 470 nm LASER. The incubator block is temperature regulated to 36.5 - 37.5℃ and contains two measuring positions, three reagent and 12 cuvette prewarming positions.
Here's an analysis of the provided text regarding the ThromboScreen® 200, structured to answer your questions:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to predicate devices (MLA-900C and MLA-1000C). The ThromboScreen® 200 must demonstrate comparable performance in terms of correlation coefficients and precision.
| Test (Reagent, Unit) | Acceptance Criteria (Implied: Comparable to Predicate) | ThromboScreen® 200 Performance (Correlation Coefficient, r) | ThromboScreen® 200 Performance (%CV for within-run precision) | ThromboScreen® 200 Performance (%CV for between-run precision) | Predicate Performance (%CV for within-run precision) | Predicate Performance (%CV for between-run precision) |
|---|---|---|---|---|---|---|
| Prothrombin Time (PT) (Thromboplastin DS, seconds) | High correlation (e.g., >0.90-0.95), comparable precision | 0.98, 0.99 | 1.9, 2.0, 2.8 (Normal); 2.3, 5.7, 3.2 (High) | 1.7% (Normal), 5.9% (Abnormal) | 1.1, 1.5, 1.0 (Normal); 2.8, 2.0, 2.8 (High) | 1.4% (Normal), 8.1% (Abnormal) |
| Prothrombin Time (Thromboplastin DS, INR) | High correlation (e.g., >0.90-0.95), comparable precision | 0.98, 0.99 | Included with PT seconds | Included with PT seconds | Included with PT seconds | Included with PT seconds |
| Activated Partial Thromboplastin Time (APTT-LS reagent, seconds) | High correlation (e.g., >0.90-0.95), comparable precision | 0.98, 0.97 | 5.1, 4.7, 3.3 (Normal); 1.6, 2.3, 2.5 (High) | 3.6% (Normal), 2.8% (Abnormal) | 1.4, 3.3, 0.9 (Normal); 2.9, 2.2, 1.2 (High) | 4.3% (Normal), 7.5% (Abnormal) |
| Clauss Fibrinogen (PH Thrombin reagent, mg/dL) | High correlation (e.g., >0.90-0.95), comparable precision | 0.99, 0.98, 0.98 | 6.7 (Low), 6.8 (Normal), 5.0 (High) | Not specified | 2.0 (Low), 2.1 (Normal), 2.8 (High) | Not specified |
| Derived Fibrinogen (Thromboplastin DS, mg/dL) | High correlation (e.g., >0.90-0.95), comparable precision | 0.99, 0.99 | 5.6 (Low), 2.5 (Normal), 4.1 (High) | Not specified | 2.2 (Low), 3.4 (Normal), 2.1 (High) | Not specified |
| Factor VIII (APTT-LS, % activity) | High correlation (e.g., >0.90-0.95), comparable precision | 0.97 | 9.6 (Low), 10.2 (Normal) | Not specified | 5.3 (Low), 4.7 (Normal) | Not specified |
| Factor V (Thromboplastin DS, % activity) | High correlation (e.g., >0.90-0.95), comparable precision | 0.97 | 2.3 (Low), 2.5 (Normal) | Not specified | 4.0 (Low), 2.0 (Normal) | Not specified |
Summary of Device Performance Meeting Acceptance Criteria:
The study demonstrates high correlation coefficients (ranging from 0.97 to 0.99) for all tested parameters when comparing the TS200 to the predicate devices. The precision data (within-run %CV and between-run %CV) for the TS200 also falls within a similar range or is sometimes better than the predicate devices, supporting the claim of substantial equivalence. For instance, for PT and APTT between-run precision, the TS200 shows comparable or better CVs than the predicate devices in several categories (e.g., PT Normal Plasma, APTT Abnormal Plasma). This suggests the device meets the implied acceptance criteria of performing comparably to legally marketed predicate devices.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Sizes for Correlation Studies (Test Set):
- Prothrombin Time (PT): Site #1 (137 samples), Site #2 (141 samples)
- Activated Partial Thromboplastin Time (APTT): Site #1 (104 samples), Site #2 (121 samples)
- Clauss Fibrinogen: Site #1 (20 samples), Site #2 (20 samples), PH (49 samples)
- Derived Fibrinogen: Site #1 (19 samples), Site #2 (47 samples)
- Factor VIII: PH (49 samples)
- Factor V: PH (45 samples)
- Sample Sizes for Precision Studies (Test Set):
- PT & APTT Between-run: Normal Plasma (n=39 for TS200, n=40 for MLA), Abnormal Plasma (n=38 for TS200 PT, n=40 for MLA PT; n=40 for TS200 APTT, n=40 for MLA APTT).
- Within-run: Not explicitly stated as a number of independent samples for each CV, but rather performed on "Low," "Normal," and "High" control levels. Usually, precision studies involve a certain number of replicates over a set number of days.
- Data Provenance: The data was collected from "in-house" (Pacific Hemostasis, PH) and "two external testing laboratories." The document states that "Specimens were evaluated from apparently healthy individuals and from patients with different pathological conditions." The country of origin is not explicitly stated, but given the submission to the FDA (USA), it's highly probable the data originated in the USA. The study is prospective in the sense that fresh clinical samples were collected and tested on both the new device and predicate devices for comparison.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of device (manual coagulation instrument) does not typically involve human expert interpretation for establishing ground truth in the same way an image analysis device would. The "ground truth" for the test set is established by the results obtained from the legally marketed predicate devices (MLA-900C and MLA-1000C), which are considered the reference standard for these in-vitro diagnostic assays. Therefore, no human experts for "ground truth interpretation" are detailed or required in this context. The experts involved are likely laboratory personnel who performed the tests on both instruments, ensuring proper methodology.
4. Adjudication Method for the Test Set
Not applicable. The study is a method comparison study where the new device's results are directly compared to those of predicate devices. There is no ambiguous output from the device that would require adjudication by experts.
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 instrument for coagulation testing, not a medical imaging device or a device involving human "readers" or AI assistance in interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the study primarily evaluates the standalone performance of the ThromboScreen® 200 instrument itself (algorithm only, if one considers the photo-optical clot detection as an "algorithm") against predicate instruments. The instrument provides a direct numerical readout (clotting time, concentration, etc.), and the study assesses its accuracy and precision in generating these results independently. Human intervention is limited to sample preparation and loading, which is standard for manual/semi-automated lab instruments.
7. The Type of Ground Truth Used
The ground truth is established by the results obtained from the legally marketed predicate devices (MLA-900C and MLA-1000C). These predicate devices are considered reliable and accurate for measuring coagulation parameters. The study assumes that if the ThromboScreen® 200 produces results highly correlated and comparable in precision to these established methods, then its measurements are also accurate.
8. The Sample Size for the Training Set
There is no mention of a "training set" in the context of this device and study. The ThromboScreen® 200 is an instrument that measures a physical property (clotting time) using photo-optical principles. It does not appear to involve machine learning or algorithms that require a separate training phase with labeled data in the way an AI-powered diagnostic might. The device's operational parameters (e.g., 470 nm laser, 37°C incubator) are fixed by its design and engineering, not trained on a data set.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no specific "training set" described for this type of device.
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JUN 21 1999
Premarket Notification 510(K) Summary ThromboScreen® 200
| 10.0 | PREMARKET NOTIFICATION 510(K) SUMMARY |
|---|---|
| Applicant: | Laura A. Worfolk, Ph.D.Pacific Hemostasis11515 Vanstory DriveHuntersville, NC 28078704-875-0494Fax # 704-875-2092 |
| Contact: | Larry Kopyta, Manager FDA Programs704-875-0494Fax # 704-875-2092 |
| Date: | April 16, 1999 |
| Trade Name: | Pacific Hemostasis ThromboScreen® 200 |
| Common Name: | Manual Coagulation Instrument |
| Classification Name: | Instrument, Coagulation (per 21 CFR section 864.5400) |
| Equivalent Devices: | MLA-900C &1000C, #K884863, #K894052 |
Description of the ThromboScreen® 200
The ThromboScreen® 200 (TS200) is a photo-optical instrument used for the performance of invitro diagnostic clotting procedures in the clinical laboratory. The instrument utilizes photo-optical principles to measure and record the time required for patient plasma specimens to clot. The ThromboScreen® 200 light source is provided by a 470 nm LASER. The incubator block is temperature regulated to 36.5 - 37.5℃ and contains two measuring positions, three reagent and 12 cuvette prewarming positions. A detailed description of the device, including an explanation of how it functions, is described in the ThromboScreen® 200 Operator's Manual, section 1, Introduction.
Intended Use of the ThromboScreen® 200
The Pacific Hemostasis ThromboScreen® 200 is a photo-optical instrument used for the performance of in-vitro diagnostic coagulation testing of citrated plasma specimens in the clinical laboratory. Coagulation testing capabilities of the device include routine clotting tests such as Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (Clauss and Derived methods), as well as PT and APTT-based factor assays.
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Summary of Substantial Equivalence Comparisons
The ThromboScreen® 200 (TS200) was compared to the MLA-900C and the MLA-1000C (K884863 & K894052, respectively). All three instruments have a similar intended use: for in-vitro diagnostic coagulation testing in the clinical laboratory. Further, the proposed device and the predicate devices have the same measurement system for clotting assays: photo-optical clot detection systems.
The TS200 is a "manual" coagulation instrument, in that the user must pipet both sample and test reagent. In contrast, the MLA-900C is semi-automated, and the MLA-1000C is a fully-automated instrument. The MLA-900C requires manual sample addition, but has an automatic pipet for reagent addition. The MLA-1000C has an automatic pipetting system, which adds both sample and test reagent. The light source for the MLA instruments is a Halogen lamp and the wavelength is set at 550 nm (for clotting assays). In contrast, the TS200 utilizes an LASER optic at 470 nm. Although differences in light source and wavelength exist, all instruments have been optimized for their light source/filter combinations. The performance data generated support this statement (Tables 1-3).
Comparison testing was performed in-house and at two external testing laboratories using Pacific Hemostasis (PH) brand reagents. Specimens were evaluated from apparently healthy individuals and from patients with different pathological conditions which are expected to affect the results for a particular assay. Table 1 summarizes the results of the comparison studies between the proposed and the predicate devices.
| Test(Reagent, Unit) | Site & Sample # | CorrelationCoefficient, r | Regression Equation |
|---|---|---|---|
| Prothrombin Time (PT)(Thromboplastin DS,seconds) | Site #1 - 137Site #2 - 141 | 0.980.99 | y = 1.078x + 0.309y = 1.076x - 0.526 |
| Prothrombin Time(Thromboplastin DS,INR) | Site #1 - 137Site #2 - 141 | 0.980.99 | y = 0.899x + 0.186y = 1.0754x - 0.1063 |
| Activated PartialThromboplastin Time*(APTT-LS reagent,seconds) | Site #1 - 104Site #2 - 121 | 0.980.97 | y = 1.328x - 0.305y = 1.072x + 4.351 |
| Clauss Fibrinogen(PH Thrombin reagent,mg/dL) | Site #1 - 20Site #2 - 20PH - 49 | 0.990.980.98 | y = 1.059x - 11.526y = 1.038x - 14.293y = 1.001x - 9.257 |
| Derived Fibrinogen(Thromboplastin DS,mg/dL) | Site #1 - 19Site #2 - 47 | 0.990.99 | y = 0.775x + 96.12y = 0.896x + 23.02 |
| Factor VIII(APTT-LS, % activity) | PH - 49 | 0.97 | y = 0.844x + 14.07 |
| Factor V,(Thromboplastin DS, %activity) | PH - 45 | 0.97 | y = 1.071x + 2.01 |
Table 1. Summary of Method Comparison Studies Between the TS200 & the MLA-900C/1000C
The predicate device used at site #1 & PH was the MLA-1000C, at site # 2 , the MLA-900C. *= APTT
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The following coefficients of variation were obtained for within-run and between-run precision studies:
| Test | Low | TS200 | MLA-900C/1000C | |||
|---|---|---|---|---|---|---|
| Normal | High | Low | Normal | High | ||
| PT | 1.9 | 2.3 | 1.1 | 2.8 | ||
| Site 1 | ||||||
| Site 2 | 2.0 | 5.7 | 1.5 | 2.0 | ||
| PH | 2.8 | 3.2 | 1.0 | 2.8 | ||
| APTT | ||||||
| Site 1 | 5.1 | 1.6 | 1.4 | 2.9 | ||
| Site 2 | 4.7 | 2.3 | 3.3 | 2.2 | ||
| PH | 3.3 | 2.5 | 0.9 | 1.2 | ||
| Clauss Fib.* | 6.7 | 6.8 | 5.0 | 2.0 | 2.1 | 2.8 |
| Derived Fib.* | 5.6 | 2.5 | 4.1 | 2.2 | 3.4 | 2.1 |
| Factor V* | 2.3 | 2.5 | 4.0 | 2.0 | ||
| Factor VIII* | 9.6 | 10.2 | 5.3 | 4.7 |
Table 2. Summary of Within-run Precision Studies, %CV
*Testing at PH only. (Shaded areas, no testing performed. Only clinically significant ranges tested.)
Table 3. Summary of PT & APTT Between-run Precision Testing
| Prothrombin Time Testing | Activated Partial ThromboplastinTime Testing | |||||||
|---|---|---|---|---|---|---|---|---|
| Normal Plasma | Abnormal Plasma | Normal Plasma | Abnormal Plasma | |||||
| TS200 | MLA | TS200 | MLA | TS200 | MLA | TS200 | MLA | |
| mean | 12.9 | 12.8 | 45.1 | 40.0 | 35.4 | 29.7 | 69.5 | 59.0 |
| SD | 0.22 | 0.18 | 2.68 | 3.24 | 1.28 | 1.27 | 1.96 | 4.41 |
| CV | 1.7% | 1.4% | 5.9% | 8.1% | 3.6% | 4.3% | 2.8% | 7.5% |
| n | 39 | 40 | 38 | 40 | 39 | 40 | 40 | 40 |
Testing performed at PH only.
In conclusion, the similar intended use, technological characteristics and performance data support the claim that the ThromboScreen® 200 is substantially equivalent to the MLA-900C and the MLA-1000C.
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PREMARKET NOTIFICATION
TRUTHFUL AND ACCURATE STATEMENT [As required by 21 CFR 807.87(j)]
I certify that, in my capacity as a Research Scientist at Pacific Hemostasis, a Fisher Scientific Company, I believe to the best of my knowledge, that all data and information submitted in the premarket notification are truthful and accurate and that no material fact has been omitted,
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មាន ១០
德国际网址 利来国际官网 利来
Laura A. Worfolk
Laura A. Worfolk, Ph.D.
K991321
*(Premarket Notification [510(k)] Number)
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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles an abstract caduceus or a series of interconnected, flowing lines, possibly representing people.
JUN 21 1999
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Laura A. Worfolk, Ph.D. Research Scientist Pacific Hemostasis 11515 Vanstory Drive Suite 125 Huntersville, North Carolina 28078-8144
Re: K991321
Trade Name: Pacific Hemostasis ThromboScreen 200 (TS200) Regulatory Class: II Product Code: KQG Dated: June 4, 1999 Received: June 7, 1999
Dear Dr. Worfolk:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Sutman
Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Page of of
510(k) Number (if known): 4991321
Device Name:__________________________________________________________________________________________________________________________________________________________________
Indications For Use:
The Pacific Hemostasis ThromboScreen® 200 is a photo-optical instrument used for the performance of in-vitro diagnostic coagulation testing in the clinical laboratory. Coagulation testing capabilities of the device include routine clotting tests such as Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (Clauss and Derived methods), as well as PT and APT-based factor assays.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Peter E. Maderi
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K99321
Prescription Use V (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.