(89 days)
MDA™ Heparin anti-X, is achromgenic assay for the quantitative determination of heparin anti-X, activity in human plasma.
Heparin is administered to prevent thrombotic comple, to prevent thrombosis following surgery) and to reduce or prevent the extension of existing thrombi (for example, in treatment of deep venous thrombosis). Heparin acts by binding to antithrombin III (AT-III), a plasma protein that inhibits coagulation enzymes including thrombin and FXa. Inhibition of these enzymes is greatly accelerated when AT-III is bound to heparin.
MDA Heparin anti-FXa measures the ability of heparin to accelerate AT-III inhibition of FXa using a chromogenic substrate. This substrate is a small peptide linked to a chromophore which is specifically cleaved by FXa to produce yellow color. The assay principle is based on the method of Teien and Lee (1,2) and uses a two-step reaction:
-
- Plasma containing heparin is mixed with buffer and AT-III, and incubated with FXa reagent for a fixed period of time. Some of the FXa is inactivated:
FXa + AT-III-Heparin (complex) ----------------------------------------------------------------------------------------------------------------------------------------------residual FXa
- Plasma containing heparin is mixed with buffer and AT-III, and incubated with FXa reagent for a fixed period of time. Some of the FXa is inactivated:
-
- Remaining active FXa cleaves chromogenic substrate to produce yellow color, monitored by measuring absorbance at 405 nm. The amount of color produced is proportional to the amount of FXa remaining and inversely proportional to the amount of heparin in the specimen plasma:
FXa + peptide-pNA -----------------> peptide + p-NO2-aniline (yellow) Reagents included in the assay kit include Buffer Concentrate, FXa reagent, Substrate reagent and AT-III
- Remaining active FXa cleaves chromogenic substrate to produce yellow color, monitored by measuring absorbance at 405 nm. The amount of color produced is proportional to the amount of FXa remaining and inversely proportional to the amount of heparin in the specimen plasma:
reagent.
Until recently, the heparins used for anticoagulant therapy were high-molecular weight (~15,000-30,000 daltons) sulfated polysaccharides that could be monitored using Activated Partial Thromboplastin Time (APTT, PTT) assay, chromogenic assays, or other methods (3). Recently, low molecular weight heparins (Mr < 15,000 daltons) have become available for clinical use. These LMW heparins can be measured using chromogenic assays, but are not readily measured by APTT.
Here's an analysis of the provided 510(k) summary regarding the MDA Heparin anti-Xₐ device, structured according to your request.
Please Note: The provided text is a 510(k) summary, not a full study report. As such, detailed information requested for items like ground truth establishment for training sets, specific expert qualifications, and MRMC study details are generally not present in these summaries. I will extract what is available and note what is not.
Acceptance Criteria and Reported Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary does not explicitly state pre-defined "acceptance criteria" in the format of a table with specific thresholds (e.g., "Slope must be between 0.95 and 1.05"). Instead, it presents the results of accuracy and precision studies and implicitly suggests that these results demonstrate substantial equivalence.
Based on the provided information, we can infer the performance metrics reported:
| Performance Metric | Reported Device Performance (MDA Heparin anti-Xₐ vs. Reference Method) | Implicit (or Common) Acceptance Range for Equivalence |
|---|---|---|
| Accuracy | ||
| Slope (Standard Heparin) | 1.06 | Typically close to 1.0 (e.g., 0.95 - 1.05) |
| Intercept (Standard Heparin) | 0.00 | Typically close to 0.0 (e.g., -0.05 - 0.05) |
| Correlation (r) (Standard Heparin) | 0.954 | Typically > 0.95 |
| Slope (Low Molecular Weight Heparin) | 0.95 | Typically close to 1.0 (e.g., 0.95 - 1.05) |
| Intercept (Low Molecular Weight Heparin) | -0.02 | Typically close to 0.0 (e.g., -0.05 - 0.05) |
| Correlation (r) (Low Molecular Weight Heparin) | 0.954 | Typically > 0.95 |
| Slope (All Specimens) | 0.98 | Typically close to 1.0 (e.g., 0.95 - 1.05) |
| Intercept (All Specimens) | 0.00 | Typically close to 0.0 (e.g., -0.05 - 0.05) |
| Correlation (r) (All Specimens) | 0.952 | Typically > 0.95 |
| Precision | (Table missing from provided text) | (No specific values or implied ranges available) |
Note on Precision Table: The precision table is garbled in the input. Therefore, I cannot report the "Reported Device Performance" for precision beyond stating that it was determined according to NCCLS guideline EPS-T2 for total and within-run precision.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Standard Heparin: 90 specimens
- Low Molecular Weight Heparin: 35 specimens
- All specimens (combined): 125 specimens
- Data Provenance: Not explicitly stated in the summary (e.g., country of origin, specific demographics). The study refers to "specimens tested." It is likely retrospective as it involves comparison to an existing commercial reagent. Whether it was prospective or retrospective is not definitively stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This is not applicable to this type of device and study. The "ground truth" for a quantitative assay like Heparin anti-Xₐ is established by comparing it to an existing, legally marketed reference method (the predicate device or another commercial chromogenic reagent). There are no human experts "establishing ground truth" in the way radiologists label images.
4. Adjudication Method for the Test Set
This is not applicable to this type of device and study. Adjudication methods (like 2+1, 3+1) are used to resolve disagreements among human reviewers in studies involving subjective interpretation (e.g., image reading). Here, the "ground truth" for comparison is an objective measurement from a reference assay.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study assesses how human performance improves with AI assistance. The MDA Heparin anti-Xₐ is a standalone laboratory assay device, not an AI-assisted interpretation tool for human readers.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done for the MDA Heparin anti-Xₐ. The study directly compared the results of the new device (MDA Heparin anti-Xₐ on an MDA 180 instrument) against a "reference method" (another commercial chromogenic reagent and system). The performance metrics (slope, intercept, correlation) reflect the standalone ability of the device to measure heparin anti-Xa activity.
7. The Type of Ground Truth Used
The "ground truth" in this context is the quantitative measurement obtained from a commercial chromogenic reagent and system that serves as the reference method. This reference method is an established, legally marketed assay for measuring Heparin anti-Xₐ. It is not expert consensus, pathology, or outcomes data.
8. The Sample Size for the Training Set
The 510(k) summary does not provide information on a "training set." This device is a diagnostic assay, and the studies described are validation studies for its performance. While the manufacturer would have developed and optimized the assay, specific details on a "training set" for an algorithm are not typically applicable or disclosed in this context for non-AI devices.
9. How the Ground Truth for the Training Set Was Established
Since no training set is described or applicable in the AI sense for this device, information on how its "ground truth" was established is not available and not relevant to the described validation studies.
{0}------------------------------------------------
510(k) SUMMARY
MAR 1 8 1997
MDA™ Heparin anti-X。
This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and the final rule under 21 CFR 807.92 published December 14, 1994.
The submitter's name, address, telephone number, a contact person, and the date the summary (a) (1) was prepared;
Submitter's Name: Submitter's Address: Submitter's Telephone: Submitter's Contact: Date 510(k) Summmary Prepared:
Organon Teknika Corporation 100 Akzo Avenue, Durham, North Carolina 27712, USA (919) 620-2373 Ron Sanyal, M. Pharm, CQE, RAC Kam December 17, 1996
The name of the device, including the trade or proprietary name if applicable, the common or (a) (2) usual name, and the classification name, if known;
| Trade/Proprietary Name: | MDA™ Heparin anti-X |
|---|---|
| Common/ Usual Name: | Heparin assay |
| Classification Name: | Heparin assay |
An identification of the legally marketed device to which the submitter claims substantial (a) (3) equivalence.
Stachrom® Heparin (K925433) Device Equivalent to:
(a) (4) A description of the device(System)
Description of MDA Heparin anti-Xa
Heparin is administered to prevent thrombotic comple, to prevent thrombosis following surgery) and to reduce or prevent the extension of existing thrombi (for example, in treatment of deep venous thrombosis). Heparin acts by binding to antithrombin III (AT-III), a plasma protein that inhibits coagulation enzymes including thrombin and FXa. Inhibition of these enzymes is greatly accelerated when AT-III is bound to heparin.
MDA Heparin anti-FXa measures the ability of heparin to accelerate AT-III inhibition of FXa using a chromogenic substrate. This substrate is a small peptide linked to a chromophore which is specifically cleaved by FXa to produce yellow color. The assay principle is based on the method of Teien and Lee (1,2) and uses a two-step reaction:
-
- Plasma containing heparin is mixed with buffer and AT-III, and incubated with FXa reagent for a fixed period of time. Some of the FXa is inactivated:
FXa + AT-III-Heparin (complex) ----------------------------------------------------------------------------------------------------------------------------------------------residual FXa
- Plasma containing heparin is mixed with buffer and AT-III, and incubated with FXa reagent for a fixed period of time. Some of the FXa is inactivated:
-
- Remaining active FXa cleaves chromogenic substrate to produce yellow color, monitored by measuring absorbance at 405 nm. The amount of color produced is proportional to the amount of FXa remaining and inversely proportional to the amount of heparin in the specimen plasma:
FXa + peptide-pNA -----------------> peptide + p-NO2-aniline (yellow) Reagents included in the assay kit include Buffer Concentrate, FXa reagent, Substrate reagent and AT-III
- Remaining active FXa cleaves chromogenic substrate to produce yellow color, monitored by measuring absorbance at 405 nm. The amount of color produced is proportional to the amount of FXa remaining and inversely proportional to the amount of heparin in the specimen plasma:
reagent.
Until recently, the heparins used for anticoagulant therapy were high-molecular weight (~15,000-30,000 daltons) sulfated polysaccharides that could be monitored using Activated Partial Thromboplastin Time (APTT, PTT) assay, chromogenic assays, or other methods (3). Recently, low molecular weight heparins (Mr < 15,000 daltons) have become available for clinical use. These LMW heparins can be measured using chromogenic assays, but are not readily measured by APTT.
{1}------------------------------------------------
(a) (5) A statement of the intended use of the device.
MDA™ Heparin anti-X, is achromgenic assay for the quantitative determination of Device Intended Use: heparin anti-X, activity in human plasma.
A summary of the technological characteristics of the new device in comparision to those of the (a) (6) predicate device.
The technological characteristics of the new device in comparison to those of the device [Stachrom® Heparin (K925433)] are given in the Table 1 below.
| PARAMETERS | ORGNON TEKNIKA'sMDA™ Heparin anti-Xₐ | DIAGNOSTICA STAGO'sStachrom® Heparin |
|---|---|---|
| CATEGORY | MDA™ Heparin anti-Xₐ is achromogenic assay. | Stachrom® Heparin assay is achromogenic assay |
| INTENDED USE | MDA™ Heparin anti-Xₐ is achromogenic assay for thequantitative determination ofheparin anti-Xa activity inhuman plasma. | Stachrom® Heparin assay is achromogenic assay forquantitative determination of theplasma level of unfractionatedheparins (UFH) or low molecularweight heparins (LMWH) by themeasurement of their anti-Xaactivity using the amidolyticmethod with chromogenicsubstrate. |
| SAMPLE | Citrated Plasma | Citrated Plasma |
| AUTOMATION | Yes(MDA 180 Instrument) | Yes(Adaptation protocol is availableon request from DiagnoticaStago) |
| TEIEN AND LEE METHOD | Yes(Two step chromogenicmeasurement based on Teien andLee method) | Yes(Two step chromogenicmeasurement based on Teien andLee method) |
TABLE 1
{2}------------------------------------------------
(b) (1) A brief discussion of the nonclinical tests submitted, reference, or relied on in the premarket notification submission for a determination of substantial equivalency.
Not Applicable
A brief discussion of the clinical tests submitted, reference, or relied on in the premarket (b)(2) notification submission for a determination of substantial equivalency.
Accuracy
Results from MDA Heparin anti-FX, reagents obtained on an MDA 180 were compared with another commercial chromogenic reagent and system for specimens tested in duplicate according to NCCLS Tentative Guideline EP9-A. The following results for slope, intercept and correlation were observed for linear regression comparing MDA Heparin anti Xs (y-axis) and the reference method (x-axis):
| Type of heparintherapy | n | Slope | Intercept | r |
|---|---|---|---|---|
| Standard heparin | 90 | 1.06 | 0.00 | 0.954 |
| Low molecularweight heparin | 35 | 0.95 | -0.02 | 0.954 |
| All specimens | 125 | 0.98 | 0.00 | 0.952 |
Precision
Total precision and within-run precision fo the MDA Heparin anti-Xa assay were determined in accordance with NCCLS guideline EPS-T2. Controls were tested in duplicate on two MDA instruments twice daily. Instruments were calibrated using duplicate determinations at the begining of each week. For each instrument, data were collected for 19-21 days, with a minimum of 38 runs and 76 measurements at each control level per instrument. The following precision was observed:
| THE BELLE FOR THE TECH TECT THE TELES LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LE LSample Sample Mean Mean(1) ========================================================================================================================================================================== | .----------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT COLLECT CONTRACT CONTRACT CONTRACT CON.. C. L. B. B. B. | Contract Concession Comparis Company Come Comments of Concession. | . SD(total) And Children a. | .---------------------------------------------------------------------------------------------------------(total). |
|---|---|---|---|---|---|
| --------------------------------------------------------- | |||||
(b) (3) The conclusion drawn from the nonclinical and clinical tests that demonstrate that the device is as safe, as effective, and performed as well or better than the legally marketed device identified in (a) (3).
In concusion, the MDA™ Heparin anti-X, has sucessfully met all aspects of clinical testing and have demonstrated that the device is safe and effective and has performed well and is substantially equivalent to the legally marketed device {Stachrom® Heparin (K925433)].
§ 864.7525 Heparin assay.
(a)
Identification. A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).(b)
Classification. Class II (performance standards).