(339 days)
INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.
The INNOVANCE™ Antithrombin assay utilizes a chromogenic measuring principle. An excess of factor Xa is added to citrated plasma. In the presence of heparin, a portion of the enzyme is complexed and inactivated by the antithrombin present in the sample. Excess, uninhibited factor Xa then cleaves a specific chromogenic substrate, causing the release of a dye. The rate of the substrate cleavage is determined by the increase in the absorbance value at 405 nm.
Acceptance Criteria and Device Performance for INNOVANCE™ Antithrombin
This response summarizes the acceptance criteria and study details for the INNOVANCE™ Antithrombin device, as presented in the provided 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary primarily focuses on demonstrating substantial equivalence to a predicate device. Therefore, the "acceptance criteria" are implied by the performance of the predicate device and the desired correlation and precision statistics.
Table 1: Performance Characteristics of INNOVANCE™ Antithrombin
| Performance Characteristic | Acceptance Criteria (Implied by Predicate) | Reported Device Performance |
|---|---|---|
| Method Comparison | ||
| Slope | ~1.0 | 1.04 |
| Intercept | ~0 (close to zero) | 0.34 |
| Correlation Coefficient (R) | High, typically ≥ 0.95 (for strong correlation) | 0.944 |
| Precision | ||
| Repeatability CV (Control Plasma N) | Low | 2.8% |
| Repeatability CV (Control Plasma P) | Low | 2.6% |
| Repeatability CV (Pathological Plasma Pool) | Low | 1.9% |
| Within-device/lab CV (Control Plasma N) | Low | 3.7% |
| Within-device/lab CV (Control Plasma P) | Low | 4.5% |
| Within-device/lab CV (Pathological Plasma Pool) | Low | 3.5% |
Study Proving Device Meets Acceptance Criteria:
The study involved comparing the INNOVANCE™ Antithrombin reagent to the legally marketed predicate device, Dade Behring Berichrom™ Antithrombin III (A) reagent (K933125), on the BCS®/BCS® XP System.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Method Comparison: n = 284 plasma samples.
- Precision:
- Control Plasma N: Tested 80 times (reported as N=80 for precision).
- Control Plasma P: Tested 80 times.
- Pathological Plasma Pool: Tested 80 times.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it's a 510(k) submission for a device manufactured in Germany (Dade Behring Marburg GmbH), some data might originate from Germany, but this is not confirmed. It is also not specified if the data was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. This device is an in vitro diagnostic (IVD) assay that quantifies a specific analyte (functionally active antithrombin) through a chromogenic reaction. The "ground truth" for the test samples is established by the validated results from the predicate device and the known concentrations of the control plasmas, not through expert human interpretation.
4. Adjudication Method for the Test Set
Not applicable. As described above, the "ground truth" for this IVD device is based on quantifiable measurements and a predicate device's performance, not on subjective expert assessment requiring adjudication.
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
Not applicable. This is an in vitro diagnostic assay, not an imaging or diagnostic AI device that involves 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 performance data presented (method comparison and precision) represents the standalone performance of the INNOVANCE™ Antithrombin assay without human intervention influencing the assay's quantitative result. The device is automated, and its performance is assessed independently.
7. The Type of Ground Truth Used
The ground truth for the method comparison study was established by the results obtained from the legally marketed predicate device, Dade Behring Berichrom™ Antithrombin III (A) reagent, when run on the same plasma samples. For precision studies, the ground truth was the known concentrations of the control plasmas (Control Plasma N, Control Plasma P, and a pathological plasma pool). This is an example of an established reference method/device and certified controls.
8. The Sample Size for the Training Set
Not applicable. This device is a chromogenic assay; it is not based on a machine learning or AI algorithm that requires a "training set" in the conventional sense. Its performance is based on chemical reactions and optical detection.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of IVD device.
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510(k) Summary for INNOVANCE™ Antithrombin
MAY 28 2009
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________
- Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation: 1.
| Manufacturer: | Dade Behring Marburg GmbH |
|---|---|
| A Siemens Company | |
| Emil-von-Behring Str. 76 | |
| 35041 Marburg, Germany |
- Siemens Healthcare Diagnostics Inc. Contact Information: 500 GBD Drive Newark, Delaware 19702 Attn: Radames Riesgo Tel: 305.480.7558 Fax: 305.552.5288
May 5. 2009 Preparation date:
INNOVANCE™ Antithrombin 2. Device Name:
Class II Classification: Product Code: JBQ Panel: Hematology
3. Identification of the Legally Marketed Device:
Dade Behring Berichrom™ Antithrombin III (A) - K933125
Device Description: 4.
The INNOVANCE™ Antithrombin assay utilizes a chromogenic measuring principle. An excess of factor Xa is added to citrated plasma. In the presence of heparin, a portion of the enzyme is complexed and inactivated by the antithrombin present in the sample. Excess, uninhibited factor Xa then cleaves a specific chromogenic substrate, causing the release of a dye. The rate of the substrate cleavage is determined by the increase in the absorbance value at 405 nm.
-> [antithrombin · heparin] antithrombin + heparin -[antithrombin · heparin] + FXa (excess) —> [antithrombin · heparin · FXa] + FXa (residual)
FXa (residual)
chromogenic FXa substrate ----------- > tripeptide + dye
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The release of dye is inversely proportional to the inhibiting activity of the antithrombin in the plasma sample, i.e. the smaller the concentration of functionally active antithrombin, the higher the absorbance signal per time unit.
5. Device Intended Use:
INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.
Medical device to which equivalence is claimed and comparison information: 6.
The INNOVANCE™ Antithrombin reagent is substantially equivalent, and has the same intended use and performance to the Dade Behring Berichrom™ Antithrombin III (A) reagent (K933125).
7. Device Performance Characteristics:
The INNOVANCE™ Antithrombin reagent was compared to the Dade Behring Berichrom™ Antithrombin III (A) reagent on the BCS®/BCS® XP System by evaluating plasma samples with antithrombin activity ranging from 4.8 to 131.3% of the norm. Regression analysis of these evaluations yielded the following equation:
| Comparative Method | n | Slope | Intercept | Correlation Coefficient |
|---|---|---|---|---|
| BerichromTM Antithrombin III (A) on the BCS ® /BCS® XP System | 284 | 1.04 | 0.34 | 0.944 |
Method Comparison Study
Precision studies were conducted with the BCS®/BCS® XP System, as described in the CLSI Guideline EP5-A2, using Control Plasma N (control plasma in the normal range) and Control Plasma P (control plasma in the pathological range) as well as a pathological plasma pool (human plasma pool in the decision range).
| Sample | Precision (N = 80) | ||
|---|---|---|---|
| Mean[% of the Norm] | Repeatability CV[%] | Within-device/lab CV[%] | |
| Control Plasma N | 95.8 | 2.8 | 3.7 |
| Control Plasma P | 31.4 | 2.6 | 4.5 |
| PathologicalPlasma Pool | 61.7 | 1.9 | 3.5 |
8. Conclusion:
The proposed INNOVANCE™ Antithrombin device is substantially equivalent to the legally marketed device based upon the correlation studies and the information above.
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Public Health Service
28 2009 MAY
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Siemens Healthcare Diagnostics Inc. c/o Mr. Radames Riesgo Regulatory Affairs and Compliance Manager 500 GBD Drive MS 514 Newark, DE 19702
Re: K081769
Trade/Device Name: INNOVANCE™ Antithrombin Regulation Number: 21 CFR 864.7060 Regulation Name: Antithrombin III assay Regulatory Class: Class II Product Code: JBQ Dated: March 23, 2009 Received: March 24, 2009
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, 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 (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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice
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Page 2 - Mr. Radames Riesgo
requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. For more information regarding the reporting of adverse events, please go to http://www.fda.gov/cdrh/mdr/.
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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours,
・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
ie m. chan
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
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、
Enclosure
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Indications for Use
510(k) Number (if known): K081769
Device Name: INNOVANCE™ Antithrombin
Indications for Use:
INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.
Prescription Use _ X (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
RemelD
Division Sign-Off
Office of In Vitro Diagnostic
Device Evaluation and Safety
K081769
510(k)
§ 864.7060 Antithrombin III assay.
(a)
Identification. An antithrombin III assay is a device that is used to determine the plasma level of antithrombin III (a substance which acts with the anticoagulant heparin to prevent coagulation). This determination is used to monitor the administration of heparin in the treatment of thrombosis. The determination may also be used in the diagnosis of thrombophilia (a congenital deficiency of antithrombin III).(b)
Classification. Class II (performance standards).