K Number
K032646
Date Cleared
2003-11-12

(77 days)

Product Code
Regulation Number
862.1117
Reference & Predicate Devices
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

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 and congestive heart failure.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers

Device Description

A device for the measurement of human proBNP in serum or plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Elecsys® proBNP Immunoassay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as strict pass/fail thresholds in the provided document. Instead, the document presents a comparative analysis against a predicate device (Elecsys proBNP (K022516)) and another predicate for conceptual use (Triage BNP (K021317)). The "acceptance" is implied by demonstrating substantial equivalence to these legally marketed devices.

The table below summarizes the performance characteristics of the Elecsys proBNP (add'l indication) and compares them to the predicate devices. The "acceptance criteria" column reflects the performance of the primary predicate for the device.

FeatureAcceptance Criteria (Elecsys proBNP K022516)Reported Device Performance (Elecsys proBNP - add'l indication)
PrecisionWithin run: - 0.9%CV @ 474 pg/mL - 1.1%CV @ 8005 pg/mL - 0.9%CV @ 13682 pg/mL 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/mLSame as Elecsys proBNP (K022516)
Hook EffectNo effect up to 300,000 pg/mlNo effect up to 300,000 pg/ml
Analytical Sensitivity5 pg/mL5 pg/mL
Limitations (Interference)Bilirubin: No interference up to 35 mg/dL Hemoglobin: No interference up to 1.4 g/dL Triglycerides: No interference up to 4000 mg/dL Biotin: No interference up to 30 ng/mL Rheumatoid Factor: No interference up to 1500 IU/mLSame as Elecsys proBNP (K022516)
Measuring Range5-35,000 pg/mL5-35,000 pg/mL

2. Sample Size Used for the Test Set and Data Provenance

The provided 510(k) summary does not contain specific details about the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It mainly focuses on the performance characteristics and comparison to predicate devices, but the underlying study details are not present.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the 510(k) summary. For an in vitro diagnostic device, "ground truth" for performance studies typically comes from reference methods, clinical diagnosis, or patient outcomes, rather than expert consensus on images or similar data.

4. Adjudication Method for the Test Set

This information is not provided in the 510(k) summary. Adjudication methods are more commonly described in studies where human interpretation of data is a variable (e.g., medical imaging studies).

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices involving human interpretation, especially AI-assisted diagnostic tools. The Elecsys proBNP Immunoassay is a laboratory-based immunoassay, not an AI-powered image analysis or interpretation tool.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the performance characteristics presented (precision, hook effect, analytical sensitivity, measuring range, limitations) represent the standalone performance of the immunoassay itself, without human-in-the-loop performance impacting the measurement results. The device quantifies a biomarker directly.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For the performance characteristics described:

  • Precision and Analytical Sensitivity: Ground truth is established by well-defined analytical methods using control materials or spiked samples with known concentrations.
  • Hook Effect: Established by testing samples with extremely high concentrations to determine if the assay accurately reports or produces a falsely low result.
  • Limitations (Interference): Established by testing samples spiked with known interferents at various concentrations.

For the clinical indications for use (aid in diagnosis of CHF, risk stratification for ACS and CHF), the underlying ground truth would be established through clinical diagnosis, patient outcomes, and potentially other diagnostic tests in clinical trials (which are not detailed in this 510(k) summary).

8. The Sample Size for the Training Set

This information is not applicable and is not provided. The Elecsys proBNP Immunoassay is a traditional immunoassay, not a machine learning or AI-based device that requires a "training set" in the computational sense. The assay is developed and validated through biochemical and analytical testing.

9. How the Ground Truth for the Training Set Was Established

As noted above, this is not applicable for this type of device.

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K032646


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Elecsys® proBNP Immunoassay

NOV 1 2 2003

510(k) Summary

IntroductionAccording 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, contactRoche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3544
Contact Person: Kay A. Taylor
Date Prepared: August 26, 2003
Device NameProprietary name: Elecsys® proBNP Immunoassay
Common name: proBNP test
Classification name: Test, Natriuretic Peptide
Device DescriptionA device for the measurement of human proBNP in serum or plasma.
Intended useFor the quantitative determination of N-terminal pro-Brain natriuretic peptide.
Indications for UseElecsys 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 and congestive heart failure.

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510(k) Summary, Continued

Substantial The device and test method contained within this premarket notification and described in the labeling is substantially equivalent to other devices legally equivalence marketed in the United States. We claim equivalence to the Roche Elecsys proBNP (K022516). Both products are intended for use in the quantitative determination of brain natriuretic peptides. The Triage BNP test (K021317) is used as predicate method for the conceptual description of how a biochemical marker can be used to provide prognostic information to a physician. Although this predicate method describes a different analyte, the description of how the test results should be interpreted with respect to the prognosis of the patient are substantially equivalent.

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Substantial equivalence comparison

The following table compares the Elecsys proBNP Immunoassay with the predicate devices.

FeatureElecsys proBNP(K022516)Elecsys proBNP(add'l indication)Triage BNP(K021317)
Intended UseImmunoassay for the in vitroquantitative determination of N-terminal pro-Brain natriureticPeptide in human serum andplasma.Immunoassay for the in vitroquantitative determination of N-terminal pro-Brain natriureticpeptide in human serum andplasma.The Triage BNP test is intended foruse with the Triage Meter for therapid in vitro quantitativemeasurement of B-Type NatriureticPeptide (BNP) in human wholeblood or plasma specimens usingEDTA as the anticoagulant.
Indication for UseThe Elecsys proBNP is intendedfor use as an aid in the diagnosis ofindividuals suspected of havingcongestive heart failure.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.The test is used as an aid in thediagnosis and assessment ofseverity of congestive heart failure.The test also is used for the riskstratification of patients with acutecoronary syndromes.
Assay ProtocolElectrochemiluminescentImmunoassaySame Elecsys proBNP (K022516)Fluorescence immunoassay
Traceability /StandardizationReference standard - purifiedsynthetic NTG-proBNP (1-76) inhuman serum matrixSame Elecsys proBNP (K022516)Not available
FeatureElecsys proBNP(K022516)Elecsys proBNP(add'l indication)Triage BNP(K021317)
Calibration IntervalE170/E2010 After 1 month when using the same reagent lot After 7 days when using the same reagent kit E1010 With every reagent kit After 7 days (20-25°C) After 3 days (25-32°C)Same Elecsys proBNP (K022516)Per lot
Sample TypeHuman serum and plasmaSame Elecsys proBNP (K022516)EDTA whole venous blood or plasma
Reagent StabilityUnopened Up to stated expiration date stored at 2-8°C Opened 12 weeks at 2-8° 8 weeks on E170 8 weeks on E2010 4 weeks on E1010 (20-25° ambient temp - up to 20 hours opened in total)Same Elecsys proBNP (K022516)In sealed pouch if stored refrigerated until the expiration date printed on the device if stored at room temperature for 14 days (w/I expiration) do not remove device from pouch until ready to use.
CalibratorElecsys proBNP CalSetSame Elecsys proBNP (K022516)Reagent Code Chip
ControlsElecsys PreciControl proBNPElecsys PreciControl proBNPElecsys PreciControl CardiacTriage BNP Controls
Result Interpretation125 pg/ml for patients younger than 75 years and 450 pg/ml for patients 75 years and older.Same Elecsys proBNP (K022516)100 pg/ml
FeatureElecsys proBNP(K022516)Elecsys proBNP(add'l indication)Triage BNP(K021317)
InstrumentElecsys 1010, Elecsys 2010 andMODULAR analytics E170 familyof analyzersSame Elecsys proBNP (K022516)Triage Meter
Measuring Range5-35,000 pg/mLSame Elecsys proBNP (K022516)5 - 5000 ng/mL

Table 3 - Comparison to Predicate Device

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Substantial The performance characteristics of the Elecsys proBNP Immunoassay and the predicate device are compared in the equivalence table below. performance characteristics

FeatureElecsys proBNP(add'l indication)Elecsys proBNP(K022516)Triage BNP(K021317)
PrecisionE170 - Within run0.9%CV @ 474 pg/mL1.1%CV @ 8005 pg/mL0.9%CV @ 13682 pg/mLE170 - Total5.8%CV @ 494 pg/mL4.1%CV @ 7827 pg/mL3.7%CV @ 13143 pg/mLE1010/2010 – Within run2.7%CV @ 175 pg/mL2.4%CV @ 355 pg/mL1.9%CV @ 1068 pg/mL1.8%CV @ 4962 pg/mLE1010/2010 - Total3.2%CV @ 175 pg/mL2.9%CV @ 355 pg/mL2.6%CV @ 1068 pg/mL2.3%CV @ 4962 pg/mLSame Elecsys proBNP (K022516)Within Day8.8%CV @ 71.3 pg/mL11.0%CV @ 629.9 pg/mL11.6%CV @ 4087.9 pg/mLTotal9.9%CV @ 71.3 pg/mL12.0%CV @ 629.9 pg/mL12.2%CV @ 4087.9 pg/mL

Table 4 - Comparison to Predicate Device - Performance Characteristics

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FeatureElecsys proBNP(add'l indication)Elecsys proBNP(K022516)Triage BNP(K021317)
Hook EffectNo effect up to 300,000 pg/mlSame Elecsys proBNP (K022516)Not available
Analytical Sensitvity5 pg/mLSame Elecsys proBNP (K022516)< 5 pg/ml
LimitationsNo 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 findingsSame Elecsys proBNP (K022516)No interference from bilirubin up to 20 mg/dL No interference from hemoglobin up to 10,000 mg/dL No interference up to cholesterol up to 1,000 mg/dL No interference up to triglycerides up to 1,000 mg/dL No significant effect from hematocrit between 27% and 51%.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/7/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal features a stylized image of an eagle with three lines representing its wings. The eagle is positioned within a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the circumference of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kay A. Taylor, MT (ASCP), RAC Regulatory Program Principal Centralized Diagnostic Submissions Roche Diagnostics Corporation 9115 Hague Road Indianapolis, Indiana 46256

NOV 1 2 2003

K032646 Re:

Trade/Device Name: Elecsys® proBNP Immunoassay Regulation Number: 21 CFR § 862.1117 Regulation Name: B-type natriuretic peptide test system (BNP) Regulatory Class: II Product Code: NBC Dated: August 26, 2003 Received: August 27, 2003

Dear Ms. Taylor:

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). 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.

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Page 2 -

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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Elecsys® proBNP Immunoassay

Indications for Use Statement

510(k) Number (if known): N/A

Device Name:

Elecsys® proBNP Immunoassay

Indications For Use:

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 and congestive heart failure.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010, Elecsys 2010 and MODULAR ANALYTICS E170 immunoassay analyzers

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use ------

(Optional Format 1-2-96)

Alberto Suts


Division Sign-Off for Jean Cooper

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K032446

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§ 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.”