(161 days)
The CoaguChek Pro APTT test is for the quantitative determination of the activated partical thromboplastin time (APTT) of freshly drawn whole blood. It is intended for health care professional use only.
The APTT is used to evaluate intrinsic pathway function. The APTT is sensitive to deficiencies of factors VIII, IX, XI, and XII, prekallikrein, high molecular weight kinogen, as well as common pathway factors (II, V, X, and fibrinogen). The APTT is useful as a screening test for coagulation function, since it is sensitive to all coagulation factors except VII, platelet factor III and calcium. Additionally, the APTT is used to monitor the effectiveness of heparin therapy. Many diseases and drugs can prolong or prevent coagulation by altering the balance of clotting factors involved in coagulation. The APTT test is initiated by inserting a CoaguChek Pro APTT test cartridge into the instrument. The instrument reads a code on the test cartridge to determine test identity and lot number. The test cartridge contains a sample application well, a reagent chamber, and a reaction path. After the instrument heats the test cartridge, a drop of fresh, whole blood is placed on the test cartridge sample application well. Blood is drawn into the reagent chamber by capillary action, where it mixes with the reagent to initiate coagulation. The blood sample moves along the reaction path until a clot forms. The laser optical system detects the clot by monitoring blood flow; endpoint is reached when the blood stops moving. The time from sample application to clot detection is the APTT. The displayed result is equivalent to laboratory plasma APTT results. Because each newly-manufactured lot is calibrated to an internal reference lot, any lot-to-lot variability between reagents is corrected electronically using information coded on the lot-specific code key.
The medical device in question is the CoaguChek Pro System, APTT Test and Controls.
1. Table of Acceptance Criteria and Reported Device Performance
| Claim | CoaguChek Plus APTT Test (Predicate) | CoaguChek Pro APTT Test |
|---|---|---|
| Mean Normal | 31 seconds | 31 seconds |
| Verified Assay Range | 18 - 150 seconds | 18 - 150 seconds |
| Displayed Assay Range | 18 - 150 seconds | 18 - 150 seconds |
| Factor Sensitivity | Factors VIII, IX, XI, XII, prekallikrein, and kininogen | Factors VIII, IX, XI, XII, prekallikrein, and kininogen |
| Verified Hematocrit Range | 25.5% - 53% | 26.5% - 53% |
| Precision with controls | Control Mean CVWithin-Day:Level 1: 55.5 sec 4.7%Level 2: 116.1 sec 4.5%Between-Day:Level 1: 56.2 sec 5.8%Level 2: 116.8 sec 3.8% | Control Mean CVOverall:Level 1: 44.2 sec 5.3%Level 2: 83.4 sec 4.7% |
| Accuracy (Regression Analysis) | Center A, n = 73: y = 1.24x - 9.9, r = 0.78Center B, n = 71: y = 1.54x - 22.5, r = 0.87Center C, n = 59: (data truncated) | Site 1, n = 55: y = 0.792x + 8.5, r = 0.89Site 2, n = 54: y = 1.134x - 0.8, r = 0.93Site 3, n = 45: (data truncated) |
Note: The provided document does not explicitly state "acceptance criteria" but rather presents a comparison of performance characteristics between the new device (CoaguChek Pro) and its predicate (CoaguChek Plus). The implication is that the CoaguChek Pro's performance characteristics demonstrate substantial equivalence to the predicate device, thereby meeting the necessary criteria for market entry. The study aims to show that the CoaguChek Pro's performance is comparable to or acceptable relative to the already marketed CoaguChek Plus system.
2. Sample size used for the test set and the data provenance
The sample sizes for the accuracy study (which serves as the "test set" for this type of device comparison) are:
- Site 1: n = 55
- Site 2: n = 54
- Site 3: n = 45
The total number of samples for the accuracy study in the CoaguChek Pro is 55 + 54 + 45 = 154 samples.
The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. However, given the nature of a 510(k) submission for a diagnostic device, these studies are typically prospective clinical performance evaluations conducted in a controlled environment, likely in the United States, by the manufacturer or affiliated research sites.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This type of in vitro diagnostic device (APTT test) typically uses a laboratory reference method or a legally marketed predicate device's results as the "ground truth" for comparison, rather than expert interpretation of images or clinical findings.
The document states: "The displayed result is equivalent to laboratory plasma APTT results." and "Test results for both methods were originally calibrated to laboratory plasma method." This indicates that the ground truth for the reported accuracy data would be a standard laboratory plasma APTT method.
Therefore, the concept of "experts" in the sense of clinicians or radiologists establishing ground truth is not directly applicable here. The ground truth is established by the highly controlled and validated laboratory reference methods for APTT, which are operated by trained laboratory professionals. The document does not specify the number or qualifications of the lab personnel operating the reference method.
4. Adjudication method for the test set
No adjudication method is mentioned. For an in vitro diagnostic device comparing its results to a laboratory reference method, an adjudication process involving multiple human readers or experts is generally not relevant. The comparison is typically a direct quantitative assessment (e.g., correlation and regression analysis) between the device's numerical output and the reference method's numerical output.
5. If a multi-reader, multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not done.
This document describes an in vitro diagnostic device for measuring Activated Partial Thromboplastin Time (APTT) in whole blood, not an AI-assisted diagnostic imaging or clinical decision support system. Therefore, the concept of human readers improving with AI assistance is not applicable. The device provides a quantitative measurement directly.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance presented is standalone/algorithm-only.
The CoaguChek Pro System provides a direct, quantitative measurement of APTT. The performance characteristics (Mean Normal, Assay Range, Factor Sensitivity, Hematocrit Range, Precision, Accuracy) describe the device's inherent analytical performance without direct human interpretation of the result in the clinical decision-making process for the purpose of the measurement itself. Healthcare professionals use the results provided by the device, but the device's detection of clot formation and calculation of APTT is an automated, standalone function.
7. The type of ground truth used
The ground truth used for performance validation is the laboratory plasma APTT method. The document explicitly states: "The displayed result is equivalent to laboratory plasma APTT results. Because each newly-manufactured lot is calibrated to an internal reference lot, any lot-to-lot variability between reagents is corrected electronically using information coded on the lot-specific code key." And "Test results for both methods [CoaguChek Pro and CoaguChek Plus] were originally calibrated to laboratory plasma method."
8. The sample size for the training set
The document does not explicitly specify a "training set" sample size. For an in vitro diagnostic device like this, the "training" equivalent would be the development and calibration of the instrument and reagents. While there's no mention of a traditional machine learning "training set," the device's internal reference lots and calibration processes are essentially what "train" the system to provide accurate results. The "Accuracy" and "Precision" data presented are considered the validation or test data, comparing the device's performance to the predicate and/or reference method.
9. How the ground truth for the training set was established
As noted above, the concept of a "training set" in the context of this device is analogous to its development and calibration. The ground truth for this process, as indicated by the text, is the laboratory plasma APTT method. The device's results are intended to be "equivalent to laboratory plasma APTT results" and were "originally calibrated to laboratory plasma method." This implies that the standard laboratory method was used as the reference to establish the correct readings and ensure lot-to-lot variability is corrected electronically.
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510(k) Summary
Introduction
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
| 1) Submitter name, address, contact | Boehringer Mannheim Corporation, doing business as Roche Diagnostics9115 Hague Rd.Indianapolis, IN 46256(317) 845-2000Contact Person: Luann Ochs |
|---|---|
| Date Prepared: October 30, 1998 | |
| 2) Device name | Proprietary name: CoaguChek Pro System, APTT Test and ControlsCommon name: Activated partial thromboplastin testClassification name: Multipurpose system for in vitro coagulation studies |
| 3) Predicate device | We claim substantial equivalence to the Biotrack monitor and APTT test cartridges and controls, K860720, K890052, K890051. The Biotrack system is also known as the Roche Diagnostics CoaguChek Plus System, APTT test and controls. |
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The APTT is used to evaluate intrinsic pathway function. The APTT is 4) Device Description sensitive to deficiencies of factors VIII, IX, XI, and XII, prekallikrein, high molecular weight kinogen, as well as common pathway factors (II, V, X, and fibrinogen). The APTT is useful as a screening test for coagulation function, since it is sensitive to all coagulation factors except VII, platelet factor III and calcium. Additionally, the APTT is used to monitor the effectiveness of heparin therapy. Many diseases and drugs can prolong or prevent coagulation by altering the balance of clotting factors involved in coagulation. The APTT test is initiated by inserting a CoaguChek Pro APTT test cartridge into the instrument. The instrument reads a code on the test cartridge to determine test identity and lot number. The test cartridge contains a sample application well, a reagent chamber, and a reaction path. After the instrument heats the test cartridge, a drop of fresh, whole blood is placed on the test cartridge sample application well. Blood is drawn into the reagent chamber by capillary action, where it mixes with the reagent to initiate coagulation. The blood sample moves along the reaction path until a clot forms. The laser optical system detects the clot by monitoring blood flow; endpoint is reached when the blood stops moving. The time from sample application to clot detection is the APTT. The displayed result is equivalent to laboratory plasma APTT results. Because each newly-manufactured lot is calibrated to an internal reference lot, any lot-to-lot variability between reagents is corrected electronically using information coded on the lot-specific code key. 5) Intended use The CoaguChek Pro APTT test is for the quantitative determination of the activated partial thromboplastin time (APTT) of freshly drawn whole blood. 6) Comparison The Roche Diagnostics CoaguChek Pro System, APTT Test and controls, is to predicate substantially equivalent to other products in commercial distribution intended device for similar use. Most notably it is substantially equivalent to the currently marketed Roche Diagnostics CoaguChek Plus System, APTT Test and controls.
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The CoaguChek Pro is similar to the CoaguChek Plus in the following items: Similarities to predicate device
| Topic | Comment |
|---|---|
| Intended Use | Both are intended for the measurement of activated partial thromboplastin time in whole blood samples. |
| Closed System | Both systems use only the instrument, reagent cartridges, and controls (liquid and electronic) that are provided by Roche and are intended to be used together. |
| Sample types | Both systems require whole blood samples, either venous or capillary. |
| Professional use | Both systems are indicated for use by health care professionals, not for over-the-counter or prescription self-testing. |
| Operating principle | Both systems use the same instrument and reagent operating principles. Instrument operating conditions are also unchanged. |
| Reagent Test Cartridges | The APTT Reagent Test cartridges are exactly the same for both monitor systems. Test cartridge design, packaging (individually foil wrapped), calibration, and storage conditions are identical. |
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Similarities to predicate device (continued)
| Topic | Comment |
|---|---|
| Assay procedure | The whole blood testing procedure is unchanged. |
| Quality control procedure | The use of the reconstituted liquid controls, or the electronic quality control cartridge is the same for both systems. |
| Specimen collection and preparation instructions | These instructions are the same for both systems. |
| Test cartridge dosing | For both systems, the test cartridge is dosed outside of the monitor, so that there is no need for cleaning of the cartridge guide or the monitor optics. |
| Maintenance | No maintenance is required for either monitor. |
| Limitations | The limitations of the procedure remain unchanged between the systems. |
| Unusual results | The instructions for action required when unusual results are obtained are the same for both systems. |
| Warnings and precautions | Warnings and precautions are unchanged. |
| Calibration of results | Test results for both methods were originally calibrated to laboratory plasma method. |
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Differences from predicate device
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The following table lists the major differences between the CoaguChek Pro and the predicate CoaguChek Plus device:
| Topic | Comment |
|---|---|
| Assays | At this time, we are only submitting the APTT test for use on the CoaguChek Pro monitor. Future tests will be submitted as separate 510(k)s. The CoaguChek Plus System includes APTT as well as a PT (prothrombin time) test. |
| Instrument models | The CoaguChek Plus System is available with one model of monitor. The CoaguChek Pro System will be available as a base model, a direct replacement for the Plus monitor, and a DM model. The DM model includes options for use in professional settings where data reporting features are required. |
| Monitor displayed self-diagnostic messages. | While both monitors provide self-diagnostic messages, the CoaguChek Plus has 22 such messages, while the CoaguChek Pro has 16 self-test messages and 29 other diagnostic messages. Please refer to the appropriate operator's manuals for the listings of the messages. |
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Performance characteristics The following chart shows a comparison of performance characteristic claims for the CoaguChek Pro APTT test and the CoaguChek Plus APTT test. Data to support the claims for the CoaguChek Pro is included in this 510(k), in section IV.
| Claim | CoaguChek PlusAPTT Test (Predicate) | CoaguChek ProAPTT Test |
|---|---|---|
| Mean Normal | 31 seconds | 31 seconds |
| Verified AssayRange | 18 - 150 seconds | 18 - 150 seconds |
| Displayed AssayRange | 18 - 150 seconds | 18 - 150 seconds |
| Factor Sensitivity | Factors VIII, IX, XI, XII,prekallikrein, andkininogen. | Factors VIII, IX, XI, XII,prekallikrein, andkininogen. |
| VerifiedHematocritRange | 25.5% - 53% | 26.5% - 53% |
| Precison withcontrols | Control Mean CVWithin-DayLevel 1 55.5 sec 4.7%Level 2 116.1 sec 4.5%Between-DayLevel 1 56.2 sec 5.8%Level 2 116.8 sec 3.8% | Control Mean CVOverallLevel 1 44.2 sec 5.3%Level 2 83.4 sec 4.7% |
| Accuracy | Center A, n = 73$y = 1.24 x - 9.9, r = 0.78$Center B, n=71$y = 1.54 x - 22.5, r = 0.87$Center C, n=59 | Site 1, n = 55$y = 0.792 x + 8.5, r = 0.89$Site 2, n = 54$y = 1.134 x - 0.8, r = 0.93$Site 3, n = 45 |
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Public Health Service
Image /page/6/Picture/2 description: The image shows a partial view of a logo or emblem. The visible portion includes a stylized representation of a human face in profile, composed of curved lines. Above the face are three curved lines that could represent hair or some other abstract design element. The word "DEPARTMENT" is partially visible along the left edge of the image, oriented vertically.
Re:
APR 1 3 1999
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
Ms. Luann Ochs Regulatory Program Manager Roche Diagnostics 9115 Hague Road Indianapolis, Indiana 46256
K983892 Trade Name: CoaguChek Pro System, APTT Test and Controls Regulatory Class: II Product Code: JPA Dated: February 5, 1999 Received: February 8, 1999
Dear Ms. Ochs:
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 (QS) 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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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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510(k) Number (if known): Device Name: CoaguChek Pro System, APTT Test and Controls Indications for Use:
The CoaguChek Pro APTT test is for the quantitative determination of the activated partical thromboplastin time (APTT) of freshly drawn whole blood. It is intended for health care professional use only.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Peter E. Madeni
(Division Sign-Off) Division of Clinical Laboratory Devices 610(k) Numiber _______________________________________________________________________________________________________________________________________________________________
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use _______
(Optional Format 1-2-96)
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§ 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.