(192 days)
For the in vitro quantitative determination of N-terminal proBrain natriuretic peptide in human serum and plasma. Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome or congestive heart failure. The test may also serve as an aid in the assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure who have stable coronary artery disease. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers.
A device for the measurement of human proBNP in serum or plasma.
Here's an analysis of the provided text regarding the Elecsys® proBNP Immunoassay's acceptance criteria and testing:
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily compares the expanded intended use device with a predicate device (K032646) which has the same core technology. The performance characteristics presented are more about consistency with the predicate rather than specific acceptance criteria against defined thresholds for new indications. However, implicit acceptance criteria can be inferred from the data provided demonstrating equivalent or better performance in the listed categories.
| Feature / Acceptance Criteria (Inferred) | Reported Device Performance (Elecsys proBNP Expanded Intended Use) |
|---|---|
| Precision | |
| E170 - Within run | 0.9%CV @ 474 pg/mL, 1.1%CV @ 8005 pg/mL, 0.9%CV @ 13682 pg/mL |
| E170 - Total | 5.8%CV @ 494 pg/mL, 4.1%CV @ 7827 pg/mL, 3.7%CV @ 13143 pg/mL |
| E1010/2010 – Within run | 2.7%CV @ 175 pg/mL, 2.4%CV @ 355 pg/mL, 1.9%CV @ 1068 pg/mL, 1.8%CV @ 4962 pg/mL |
| E1010/2010 – Total | 3.2%CV @ 175 pg/mL, 2.9%CV @ 355 pg/mL, 2.6%CV @ 1068 pg/mL, 2.3%CV @ 4962 pg/mL |
| Hook Effect | No effect up to 300,000 pg/ml |
| Analytical Sensitivity | 5 pg/mL |
| Interference (Limitations) | No interference from bilirubin up to 35 mg/dL, hemoglobin up to 1.4 g/dL, triglycerides up to 4000 mg/dL, biotin up to 30 ng/mL, rheumatoid factor up to 1500 IU/mL. Sample should not be taken until 8 hours after high biotin doses (>5 mg/dL). Rare interference from high titers of anti-streptavidin and ruthenium. |
| Measuring Range | 5-35,000 pg/mL |
| Result Interpretation | 125 pg/ml for patients younger than 75 years and 450 pg/ml for patients 75 years and older. |
The "study that proves the device meets the acceptance criteria" for the expanded indications primarily relies on three literature articles that support the clinical utility of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in the new indications (risk stratification in stable and unstable CAD, and assessment of increased risk of cardiovascular events/mortality in patients at risk for heart failure with stable CAD). The provided text confirms that the analytical performance characteristics (precision, hook effect, analytical sensitivity, limitations, measuring range, result interpretation) of the current device are the same as an existing predicate device (K032646), which presumably already met its own set of acceptance criteria. The submission is for an expanded intended use, implying the analytical performance itself is not a new challenge, but rather the clinical validation of the biomarker for additional conditions.
2. Sample Size Used for the Test Set and Data Provenance:
- Clinical Studies (Expanded Indications): The document does not explicitly state the sample size, provenance (country, retrospective/prospective), or specific details of the patient populations for the three literature articles cited. These are external peer-reviewed publications.
-
- Schnabel R, et al. (2005) - AtheroGene Study cohort.
-
- Kragelund C, et al. (2005) - Copenhagen.
-
- Ndrepepa G, et al. (2005) - Unknown.
-
- Analytical Performance Studies (Precision, Hook Effect, etc.): The sample sizes for the internal analytical performance studies are not provided. The text states "Elecsys proBNP (add'l indication)" and refers to the predicate device's performance, implying either that new studies for these parameters were performed and yielded identical results, or that the existing data for the predicate device is considered applicable due to the identical assay protocol, traceability, calibrator, controls, and instrument.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Clinical Studies (Expanded Indications): This information would be within the cited literature articles, not directly in this 510(k) summary. These studies involve clinical endpoints and patient outcomes, which are not typically "expert-established ground truth" in the same way an image interpretation might be. The "ground truth" would be the observed clinical events (e.g., cardiovascular events, mortality) and patient diagnoses.
- Analytical Performance Studies: Not applicable. Ground truth for these studies relates to spiked samples or reference materials, not expert consensus.
4. Adjudication Method for the Test Set:
- Clinical Studies (Expanded Indications): This information would be within the cited literature articles. Clinical trials often have adjudication committees for endpoints, but the specific methods are not detailed here.
- Analytical Performance Studies: Not applicable.
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:
- No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic imaging or interpretation device. Therefore, the concept of "human readers improving with AI assistance" is not applicable. The device provides a quantitative measurement of a biomarker.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense, a "standalone" performance was done for the analytical characteristics. The device itself provides a quantitative measurement (pg/mL) directly. The analytical performance metrics (precision, sensitivity, interference, hook effect, measuring range) are intrinsic to the device's function and were demonstrated without human intervention in the measurement process. The interpretation of these results for clinical decision-making is then done by a healthcare professional, but the measurement itself is automated.
7. The type of ground truth used:
- Clinical Studies (Expanded Indications):
- For the diagnosis of congestive heart failure and risk stratification of acute coronary syndrome/congestive heart failure: Presumed clinical diagnosis and patient outcomes/events (e.g., mortality, cardiovascular events) as defined and adjudicated within the cited clinical studies.
- For assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure with stable coronary artery disease: Presumed observed cardiovascular events and mortality over follow-up periods, as defined in the cited literature.
- Analytical Performance Studies: Presumed reference methods, defined concentrations in spiked samples, or reference materials for accuracy, precision, sensitivity, and interference studies.
8. The Sample Size for the Training Set:
- Not Applicable / Not Provided. For an immunoassay like this, there isn't typically a "training set" in the machine learning sense. The assay is built and validated based on biochemical principles, antibody specifications, and instrument calibration. The clinical utility is established in clinical trials, but these aren't "training sets" for an algorithm. If referring to assay development, that data is not provided.
9. How the Ground Truth for the Training Set was Established:
- Not Applicable / Not Provided. As mentioned above, "training set" is not a direct concept for this type of IVD. The development and validation of the immunoassay itself relies on established analytical chemistry and immunoassay principles, using characterized reagents and reference standards to establish the analytical performance.
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K05/382
Elecsys® proBNP Immunoassay Expanded Intended Use Submission
:
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. |
|---|---|
| Submitter name, address, contact | Roche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3544 |
| Contact Person: Theresa M. Ambrose | |
| Date Prepared: Nov 28, 2005 | |
| Device Name | Proprietary name: Elecsys® proBNP Immunoassay |
| Common name: proBNP test | |
| Classification name: Test, Natriuretic Peptide | |
| Description | A device for the measurement of human proBNP in serum or plasma. |
| Intended use | Immunoassay for the in vitro quantitative determination of N-terminal pro-Brain Natriuretic Peptide in human serum and plasma. |
| Indications for Use | Elecsys proBNP is used as an aid in the diagnosis of individuals suspected of having congestive heart failure. The test is further indicated for the risk stratification of patients with acute coronary syndrome or congestive heart failure. The test may also serve as an aid in the assessment of increased risk of cardiovascular events and mortality in patients at risk for heart failure who have stable coronary artery disease. |
| Substantial equivalence | The device and test method contained within this premarket notification and described in the labeling is substantially equivalent to other devices legally marketed in the United States. We claim equivalence to the Roche Elecsys proBNP (K032646). |
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The following table compares the Elecsys proBNP Test System with the Substantial predicate device. equivalence comparison
| Feature | Elecsys proBNPExpanded Intended Use | Elecsys proBNP(K032646) Predicate |
|---|---|---|
| Intended Use | Immunoassay for the in vitroquantitative determination of N-terminal pro-Brain natriureticPeptide in human serum andplasma. | same |
| Indication for Use | Elecsys proBNP is used as an aidin the diagnosis of individualssuspected of having congestiveheart failure. The test is furtherindicated for the risk stratificationof patients with acute coronarysyndrome or congestive heartfailure. The test may also serve asan aid in the assessment ofincreased risk of cardiovascularevents and mortality in patients atrisk for heart failure who havestable coronary artery disease. | Elecsys proBNP is used as an aidin the diagnosis of individualssuspected of having congestiveheart failure. The test is furtherindicated for the risk stratificationof patients with acute coronarysyndrome and congestive heartfailure. |
| Assay Protocol | ElectrochemiluminescentImmunoassay | Same |
| Traceability /Standardization | Reference standard - purifiedsynthetic NTG-proBNP (1-76) inhuman serum matrix | Same |
| Calibration Interval | E170/E2010• After 1 month when using thesame reagent lot• After 7 days when using thesame reagent kitE1010• With every reagent kit• After 7 days (20-25°C)• After 3 days (25-32°C) | Same |
| Sample Type | Human serum and plasma | Same |
Table 3 - Comparison to Predicate Device
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| Feature | Elecsys proBNPExpanded Intended Use | Elecsys proBNP(K032646) Predicate |
|---|---|---|
| Reagent Stability | Unopened• Up to stated expiration datestored at 2-8°COpened• 12 weeks at 2-8°• 8 weeks on E170• 8 weeks on E2010• 4 weeks on E1010 (20-25°ambient temp - up to 20 hoursopened in total) | Same |
| Calibrator | Elecsys proBNP CalSet | Same |
| Controls | Elecsys PreciControl Cardiac | Elecsys PreciControl proBNPElecsys PreciControl Cardiac |
| Result Interpretation | 125 pg/ml for patients youngerthan 75 years and 450 pg/ml forpatients 75 years and older. | Same |
| Instrument | Elecsys 1010, Elecsys 2010 andMODULAR analytics E170 familyof analyzers | Same |
| Measuring Range | 5-35,000 pg/mL | Same |
.
.
:
.
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The performance characteristics of the Elecsys proBNP Immunoassay and the predicate Substantial equivalence table below. performance characteristics
| Feature | Elecsys proBNP(add'l indication) | Elecsys proBNP(K022516) |
|---|---|---|
| Precision | E170 - Within run | Same |
| 0.9%CV @ 474 pg/mL | ||
| 1.1%CV @ 8005 pg/mL | ||
| 0.9%CV @ 13682 pg/mL | ||
| E170 - Total | ||
| 5.8%CV @ 494 pg/mL | ||
| 4.1%CV @ 7827 pg/mL | ||
| 3.7%CV @ 13143 pg/mL | ||
| E1010/2010 – Within run | ||
| 2.7%CV @ 175 pg/mL | ||
| 2.4%CV @ 355 pg/mL | ||
| 1.9%CV @ 1068 pg/mL | ||
| 1.8%CV @ 4962 pg/mL | ||
| E1010/2010 – Total | ||
| 3.2%CV @ 175 pg/mL | ||
| 2.9%CV @ 355 pg/mL | ||
| 2.6%CV @ 1068 pg/mL | ||
| 2.3%CV @ 4962 pg/mL |
Table 4 - Comparison to Predicate Device - Performance Characteristics
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| Feature | Elecsys proBNP(add'l indication) | Elecsys proBNP(K022516) |
|---|---|---|
| Hook Effect | No effect up to 300,000 pg/ml | Same |
| Analytical Sensitvity | 5 pg/mL | Same |
| Limitations | No interference from bilirubin up to 35 mg/dL No interference from hemoglobin up to 1.4 g/dL No interference from triglycerides up to 4000 mg/dL No interference with biotin up to 30 ng/mL No interference from rheumatoid factor up to 1500 IU/mL In patients receiving high biotin doses > 5 mg/dL, sample should not be taken until 8 hours after administration. Rare occurrence of interference from high titers of anti-streptavidin and ruthenium Use in conjunction with patient medical history, clinical exam and other findings | Same |
Three literature articles were provided in support of the expanded intended Support for claim use:
-
- Schnabel R, Rupprecht HJ, Lackner KJ, Lubos E, Bickel C, et al. Analysis of N-Terminal-pro-Brain Natriuretic Peptide and C-Reactive Protein for Risk Stratification in Stable and Unstable Coronary Artery Disease: Results from the AtheroGene Study. European Heart Journal, 2005. 26(3):241-249.
-
- Kragelund C, Groenning B, Kober L, Hildebrandt P and Steffensen R. N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease. The New England Journal of Medicine, 2005. 352(7):666-675.
-
- Ndrepepa G, Braun S, Niemoller K, Mehilli J, von Beckerath N, et al. Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Chronic Stable Angina. Circulation, 2005. 112:2102-2107.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three abstract shapes resembling birds in flight. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
2005 DEC 5
Theresa M. Ambrose, PhD, RAC Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road Indianapolis, IN 46250
Re: K051382
Trade/Device Name: Elecsys proBNP Immunoassay Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: October 14, 2005 Received: October 17, 2005
Dear Dr. Ambrose:
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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
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 promative results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours,
Alberto Guez
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K051382
Elecsys proBNP Immunoassay Device Name:
Indications For Use:
For the in vitro quantitative determination of N-terminal proBrain natriuretic peptide in human serum and plasma.
peptial in hamall ver an aid in the diagnosis of individuals suspected of having Electy proDities is as a the test is further indicated for the risk stratification of contents with acute coronary syndrome or congestive heart failure . The test may patients with assessment of increased risk of cardiovascular events and anso ser re as an and and failure who have stable coronary artery disease.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers
Prescription Use XXX
AND/OR
Over-The-Counter Use
(Part 21 CFR 801 Subpart D)
(21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
CHS
vision Sign-Off
Page 1 of
Office of In Vitro Diagnostic Device Evaluation and Safet
§ 862.1117 B-type natriuretic peptide test system.
(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”