(221 days)
HemosIL INR Validate is a tri-level quality control intended to monitor the accuracy of INR (International Normalized Ratio) reporting with designated HemosIL PT reagents on IL Coagulation Systems in conjunction with the ISIweb software.
HemosIL ISI Calibrate is a set of four certified plasmas intended to establish a laboratory's instrument/ reagent specific local ISI (International Sensitivity Index) and Mean Normal Prothrombin Time (MNPT) with designated Hemos)L PT reagents on IL Coagulation Systems in conjunction with the ISIweb software.
ISIweb Software is a web-based service to customers, used in conjunction with HemosIL INR Validate and HemosIL ISI Calibrate with designated HemosIL PT reagents on IL Coagulation Systems; whereby the PT seconds and INR results can be entered and calculated through a web-based interface (ISIweb software).
For in vitro diagnostic use.
HemosIL INR Validate: The HemosIL INR Validate set consists of three control plasmas (Levels 1-3) with assigned INR (International Normalized Ratio) Reference Values in the range of 1.6 - 5.0, prepared using lyophilized citrated plasma from human donors on stable anti-vitamin K therapy (AVK). The reference INR values for each Level are reagent-specific for the IL coagulation systems. The plasma factors (II, VII, IX, X, PC & PS) in these controls are similar to levels normally expected in plasma from patients undergoing long-term oral anticoagulant therapy, together with the proteins induced by vitamin K antagonists (PIKVA inhibitors). The control plasmas of HemosIL INR Validate are run on a local instrument/reagent system using the manufacturer's lot-specific label ISI value and the laboratory's locally establishied lot-specific Mean Normal Prothrombin Time (MNPT). If the mean INRs of all the controls are within ± 15% of their assigned INR Reference Values as determined through the ISIweb, the PT/INR system is verified. If the mean INRs of the controls exceed ± 15% of their assigned INR Reference Values as determined through the ISIweb a new local ISI calibration is recommended using HemosIL ISI Calibrate. Verification of the new local ISI and MNPT is then performed by running the HemosIL INR Validate control plasmas a second time on the same instrument/reagent system with the local ISI and MNPT.
HemosIL ISI Calibrate: The HemosIL ISI Calibrate set contains four calibration plasmas (Levels A-D) with assigned INR (International Normalized Ratio) Reference Values in the range of 0.9 - 5.0 for standardizing the PT test on IL Coagulation Systems. These INR Reference Values are reagent specific for the IL Coagulation Systems. Level A is a lyophilized normal human pool produced from the selected citrated plasmas of healthy donors. Levels B-D are lyophilized citrated plasmas produced from a pool of human donors on long-term oral anticoagulant therapy (antivitamin K: AVK). The plasma factors (II, VII, IX, X, PC, & PS) are similar to those levels normally expected in plasma from patients undergoing long term oral anticoagulant therapy together with protein induced by vitamin K antagonists (PIVKA inhibitors). The calibrate plasmas from HemosIL ISI Calibrate are run on the laboratory's IL instrument/reagent system to establish a local ISI. The PT (sec) data is entered into the ISIweb, which generates a calibration curve from the PT and the INR Reference Values by plotting an orthogonal regression of LogINR (X-axis) vs. LogPT (Y-axis). The ISI and Mean Normal Prothrombin Time (MNPT) are derived from the slope and y-intercept of the curve as: ISI = T slope MNP, MNP = T O y-intercept.
ISIweb Software: When used in conjunction with HemosIL INR Validate, ISIweb will automatically calculate the mean INR for each control level and verify that the mean INR for each control level is within ± 15% of the assigned INR Reference Value. When used in conjunction with HemosIL ISI Calibrate, ISIweb will automatically calculate the mean PT and %CV value for each level. If the %CV for each level passes % CV specifications, the ISIweb generates a calibration curve from the PT and INR Reference Values by plotting an orthogonal regression of LogINR (X-axis) vs. LogPT (y-axis).
Here's an analysis of the provided text to extract information about the acceptance criteria and the study that proves the device meets those criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the HemosIL INR Validate device revolve around the accuracy of INR reporting. The study mentioned focuses on the precision of the devices (HemosIL INR Validate and HemosIL ISI Calibrate).
| Device/Parameter | Acceptance Criteria | Reported Device Performance (Precision Study) |
|---|---|---|
| HemosIL INR Validate | ||
| Accuracy of INR reporting (mean INRs of controls) | If the mean INRs of all the controls are within ± 15% of their assigned INR Reference Values as determined through the ISIweb, the PT/INR system is verified. If the mean INRs exceed ± 15%, a new local ISI calibration is recommended. | Precision Data (PT in Seconds, %CV) - Note: Actual INR values or deviation from assigned INR reference values are not explicitly provided in the summary data for direct comparison to the ±15% criterion. The precision data shows the consistency of PT measurements, which contribute to INR accuracy. |
Examples for HemosIL INR Validate (across various reagents/instruments/levels):
- Within-Run %CV ranged from 0.4% to 4.1%.
- Total %CV ranged from 1.5% to 4.4%.
(Specific examples from the table are extensive, but these ranges represent the overall device performance as reported in the precision study.)
Examples (RecombiPlasTin, ACL TOP, Level 1): Mean 28.1s, Within-Run %CV 1.2, Total %CV 1.5.
(RecombiPlasTin 2G, ACL TOP, Level 3): Mean 53.2s, Within-Run %CV 4.1, Total %CV 4.4. |
| HemosIL ISI Calibrate | | |
| %CV for each calibration level | If the %CV for each level passes % CV specifications, the ISIweb generates a calibration curve. (Specific %CV specifications are not explicitly stated in the provided text, but implied as a pass/fail condition for calibration curve generation). | Precision Data (PT in Seconds, %CV)
Examples for HemosIL ISI Calibrate (across various reagents/instruments/levels):
- Within-Run %CV ranged from 0.1% to 4.4%.
- Total %CV ranged from 1.1% to 4.9%.
(Specific examples from the table are extensive, but these ranges represent the overall device performance as reported in the precision study.)
Examples (RecombiPlasTin, ACL TOP, Level A): Mean 12.1s, Within-Run %CV 1.2, Total %CV 1.3.
(RecombiPlasTin 2G, ACL TOP, Level D): Mean 50.8s, Within-Run %CV 4.4, Total %CV 4.9. |
Note: The provided text outlines the procedure for verifying the PT/INR system using HemosIL INR Validate (the ±15% criterion), but the "Summary Performance Data" presented is primarily a precision study showing %CV values for PT measurements. It implies that these precision levels are acceptable for the device's intended function, but does not directly report on the ±15% INR accuracy for HemosIL INR Validate or the specific %CV passing specifications for HemosIL ISI Calibrate used to generate the calibration curve.
2. Sample Size for the Test Set and Data Provenance
- Sample Size for Test Set: The precision study was conducted with N=80 per level for both HemosIL INR Validate (3 levels) and HemosIL ISI Calibrate (4 levels).
- Data Provenance: Not explicitly stated (e.g., country of origin). The study involved "representative IL Coagulation Systems" and "HemosIL PT reagents." The nature of the study (precision of controls and calibrators) suggests prospective testing within a laboratory setting.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
Not applicable. This device is a diagnostic control/calibrator and software for an in vitro diagnostic test (PT/INR). The "ground truth" here would be the assigned INR Reference Values for the control plasmas and calibrators by the manufacturer. These values are established through rigorous manufacturing and assay procedures, not typically by expert adjudication of individual test results in the way it applies to image interpretation or clinical diagnosis. The reference values are inherent to the product.
4. Adjudication Method for the Test Set
Not applicable. As noted above, the "ground truth" for the test samples are the assigned reference values of the control and calibrator plasmas, not a consensus derived from expert adjudication of individual patient results.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size
No. This is not an AI-assisted diagnostic device for human interpretation (e.g., image reading). It's a quality control and calibration system for a coagulation analyzer. Therefore, an MRMC comparative effectiveness study with human readers assisting with AI is not relevant and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, in a sense. The "ISIweb Software" performs automated calculations for INR verification and ISI calibration. The precision study evaluated the performance of the HemosIL INR Validate and HemosIL ISI Calibrate products in conjunction with IL Coagulation Systems, where the ISIweb software processes the raw PT data. The output (Mean Seconds, %CV) is from the system (reagents + instrument + software) functioning in a "standalone" or automated manner for its intended purpose. The software processes objective measurements (PT seconds) and applies pre-defined algorithms to calculate INR, ISI, MNPT, and verify control results.
7. The Type of Ground Truth Used
The ground truth used for these devices is primarily assigned reference values for the control plasmas and calibrator plasmas. These values are established by the manufacturer (Instrumentation Laboratory Co.) and are reagent-specific for the IL Coagulation Systems. For the HemosIL INR Validate, the controls have "assigned INR Reference Values." For the HemosIL ISI Calibrate, the calibrators also have "assigned INR Reference Values" which are used to establish a local ISI and MNPT. These reference values are traceable to international standards (e.g., WHO International Reference Preparations for Thromboplastins, as implied by the use of ISI).
8. The Sample Size for the Training Set
Not applicable in the conventional sense of an AI/ML training set. This device is a quality control and calibration system, not a machine learning algorithm that is "trained" on a dataset. The ISIweb software applies established mathematical algorithms (e.g., orthogonal regression for LogINR vs. LogPT) rather than a learned model.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of machine learning. The algorithms used by the ISIweb software are based on established scientific principles for INR and ISI calculation, following guidelines like CLSI H54-A and ISTH. The "ground truth" for these calculations is the mathematical relationship derived from these guidelines and the assigned reference values of the calibrator and control plasmas.
§ 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.