Immunoassay for the in vitro quantitative determination of N-terminal pro-Brain natriuretic peptide in human serum and plasma. The Elecsys proBNP Immunoassay is intended for use as an aid in the diagnosis of individuals suspected of having congestive heart failure.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of analyzers.

Device Description

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

AI/ML Overview

The provided text describes the Elecsys proBNP Immunoassay and its substantial equivalence to a predicate device, the Biosite Triage BNP Test. However, it does not contain a detailed study report that would typically outline acceptance criteria and prove the device meets them with specific performance metrics and study designs. Instead, it provides a comparison of features and general performance characteristics between the new device and the predicate.

Therefore, I cannot fully answer all points of your request based solely on the provided input. I will highlight what information is available and what is missing.

Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative, pre-defined manner for clinical performance. Instead, it compares the Elecsys proBNP Immunoassay against a predicate device based on various features and analytical performance metrics. The implicit "acceptance" is based on demonstrating substantial equivalence to the legally marketed predicate device (Biosite Triage BNP Test, cleared under K003475).

Here's a table based on the provided comparison, highlighting analytical performance characteristics. It's crucial to note these are reported characteristics, not explicit acceptance criteria with pass/fail thresholds against which a study directly demonstrated compliance.

Feature	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (Elecsys proBNP Immunoassay)
Intended Use	Measurement of B-Type Natriuretic Peptide (BNP).	Quantitative determination of N-terminal pro-Brain natriuretic peptide.
Indication for Use	An aid in the diagnosis of congestive heart failure in patients age 55 and older.	An aid in the diagnosis of individuals suspected of having congestive heart failure.
Assay Protocol	Fluorescence Immunoassay	Electrochemiluminescent immunoassay
Measuring Range	5-1300 pg/mL	5-35,000 pg/mL
Precision	Within-run: 9.4-15.2 %CV (from 28.8-1080.4 pg/mL)Total: 10.1-16.2 %CV	E170: Within-run: 0.8-1.1 %CV (from 208-13,682 pg/mL); Total: 3.6-5.8% CV (from 200-13143 pg/mL)E1010/2010: Within-run: 1.8-2.7 %CV (from 175-4962 pg/mL); Total: 2.2-3.2 %CV (from 175-4962 pg/mL)
Hook Effect	NA (not mentioned for predicate)	No high dose hook effect up to 300,000 pg/mL
Analytical sensitivity (LDL)	5 pg/mL	5 pg/mL
Interference (Bilirubin)	No interference up to 20 mg/dL	No interference up to 35 mg/dL
Interference (Hemoglobin)	No interference up to 10000 mg/dL (severely hemolyzed specimens should be avoided)	No interference up to 1.4 g/dL
Interference (Triglycerides)	No interference up to 1000 mg/dL	No interference up to 4000 mg/dL
Interference (Cholesterol)	No interference up to 1000 mg/dL	NA (not mentioned for Elecsys proBNP)
Interference (Biotin)	NA (not mentioned for predicate)	No interference up to 30 ng/mL. Caution for high biotin doses (> 5 mg/dL) requiring sample collection 8 hours post-administration.
Interference (Rheumatoid Factor)	NA (not mentioned for predicate)	No interference up to 1500 IU/mL
Traceability/Standardization	Purified BNP preparation based on mass of analyte present in EDTA plasma.	Reference standard - purified synthetic NTG-proBNP (1-76) in human serum matrix.
Expected Values/Cut-offs	Age and sex-related descriptive statistics provided. Cut-off 100 pg/mL recommended.	Age and sex-related descriptive statistics provided. Cut-offs of 125 pg/ml for patients younger than 75 years and 450 pg/ml for patients 75 years and older are recommended. (Note: Different cut-offs indicate different analytes/assays, but both provide relevant clinical guidance).

Study Details

The provided text does not contain a detailed study report that would include information on sample sizes, data provenance, expert ground truth, adjudication methods, or specific comparative effectiveness studies.

Based on the information available:

Sample size used for the test set and the data provenance: Not explicitly stated. The document refers to "performance characteristics" and "limitations," implying studies were conducted to determine these, but it does not specify the number of samples or their origin.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This is an immunoassay measuring a biomarker concentration, not an imaging device requiring expert interpretation for ground truth. The "ground truth" for analytical performance would be against known concentrations of the analyte or comparison to a reference method.
Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable for this type of immunoassay.
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: Not applicable. This is an in vitro diagnostic (IVD) immunoassay, not an AI-powered diagnostic imaging device involving human readers or AI assistance.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The device is a standalone immunoassay measuring ProBNP levels. Its performance is inherent to the assay itself.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.): For this type of device, ground truth for analytical performance would typically be established by:
- Known concentrations: For precision, linearity, analytical sensitivity/detection limit.
- Spiking studies: For interference.
- Comparison to a gold standard or reference method: For accuracy and correlation.
- Clinical correlation: Showing the measured biomarker levels correlate with the presence or absence of congestive heart failure. The document indicates its use "as an aid in the diagnosis," suggesting clinical correlation studies formed part of its validation.
The sample size for the training set: Not applicable. This is not a machine learning or AI device that uses training sets in the computational sense. Instead, the "training" for such a device involves developing and optimizing the assay reagents and protocols.
How the ground truth for the training set was established: Not applicable.

In summary, the provided document is a 510(k) summary focused on demonstrating substantial equivalence of an immunoassay to an existing device. It highlights comparative features and analytical performance specifications rather than a detailed study report with specific acceptance criteria and clinical validation study designs.

Summary

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Roche Diagnostic Corporations 11/12/02

K022516- Elecsys ProBNP

510(k) Summary

NOV 1 9 2002

Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
Submittername, address,contact	Roche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3544Contact Person: Kay A. TaylorDate Prepared: September 12, 2002
Device Name	Proprietary name: Elecsys® proBNP ImmunoassayCommon name: proBNP testClassification name: Test, Natriuretic Peptide
DeviceDescription	A device for the measurement of human proBNP in serum or plasma.
Intended use	For the quantitative determination of N-terminal pro-Brain natriuretic peptide.
Indications forUse	An aid in the diagnosis of individuals suspected of having congestive heartfailure.

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Roche Diagnostic Corporations 11/12/02

510(k) Summary, Continued

The Elecsys proBNP Immunoassay is substantially equivalent to other Substantial devices legally marketed in the United States. We claim equivalence to the equivalence Biosite Triage BNP Test cleared under K003475. Both products are intended for use in the quantitative determination of brain natriuretic peptides.

The following table compares the Roche Elecsys proBNP Immunoassay with Substantial equivalence the predicate device. comparison

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Feature	Elecsys proBNPImmunoassay	Biosite Triage BNP Test(predicate)
Intended Use	For the quantitativedetermination of N-terminalpro-Brain natriuretic peptide.	Measurement of B-TypeNatriuretic Peptide (BNP).
Indication for Use	An aid in the diagnosis ofindividuals suspected ofhaving congestive heartfailure.	An aid in the diagnosis ofcongestive heart failure inpatients age 55 and older
Assay Protocol	Electrochemiluminescentimmunoassay	Fluorescence Immunoassay
Traceability / Standardization	Reference standard - purifiedsynthetic NTG-proBNP (1-76) in human serum matrix	Purified BNP preparationbased on mass of analytepresent in EDTA plasma
Calibration Interval	E170/E2010After 1 month when usingthe same reagent lot After 7 days when usingthe same reagent kitE1010 With every reagent kit After 7 days (20-25°C) After 3 days (25-32°C)	Each kit
Sample Type	Human serum and plasma	Human whole blood andEDTA plasma
Calibrator	Elecsys proBNP CalSet	Electronic code chip
Controls	Elecsys PreciControl proBNP	Triage® BNP Controls

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510(k) Summary, Continued, Continued

Feature	Elecsys proBNPImmunoassay	Biosite Triage BNP Test(predicate)
Reagent Stability	Unopened• Up to stated expirationdate stored 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 20hours opened in total)	• Up to stated expirationdate when stored at 2-8°C.• 14 days at ambienttemperature
Expected Values	• Age and sex-relateddescriptive statisticsprovided• Cut-offs of 125 pg/ml forpatients younger than 75years and 450 pg/ml forpatients 75 years andolder are recommended.	• Age and sex-relateddescriptive statisticsprovided• Cut-off 100 pg/mLrecommended
Instrument	Elecsys family of analyzers(Elecsys 1010, Elecsys 2010and Elecsys E170MODULAR AnalyticsImmunoassay Analyzers)	Triage® Meter
Measuring Range	5-35,000 pg/mL	5-1300 pg/mL
Feature	Elecsys proBNP Immunoassay	Biosite Triage BNP Test(predicate)
Precision	E170Within-run 0.8-1.1 %CV from 208-13,682 pg/mL Total 3.6-5.8% CV from 200-13143 pg/mLE101/2010 Within-run 1.8-2.7 %CV from 175-4962 pg/mL Total 2.2-3.2 %CV from 175-4962 pg/mL	Average within-run 9.4-15.2 %CV from 28.8-1080.4 pg/mL Average total 10.1-16.2 %CV
Hook Effect	No high dose hook effect up to300,000 pg/mL	NA
Analyticalsensitivity (LDL)	5 pg/mL	5 pg/mL
Limitations/Warnings/Precautions	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	No interference from bilirubin up to 20 mg/dL. No interference from hemoglobin up to 10000 mg/dLSeverely hemolyzed specimens should be avoided. No interference from triglycerides up to 1000 mg/dL No interference from cholesterol up to 1000 mg/dL Blood concentrations of natriuretic peptides may be elevated in patients with acute myocardial infarction, patients that are candidates for renal dialysis, and patients that have undergone renal dialysis Results should be evaluated in the context of all the clinical and laboratory data available

Continued on next page

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Roche Diagnostic Corporations 11/12/02

100 - 100 - 100 -

510(k) Summary, Continued

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right. The profiles are stacked on top of each other and are connected by a flowing line.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Kay A. Taylor Regulatory Program Principal Centralized Diagnostic Submissions Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457

NOV 1 9 200

Re: K022516

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; JIT; JJX Dated: October 23, 2002 Received: October 24, 2002

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.

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Page 2 -

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 (OS) 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 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). Other general information on your responsibilities under the Act may be obtained 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,

Daniel H. L.

Steven 1. 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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Indications for Use Statement

k 022

510(k) Number (if known): Nes

Device Name:

Elecsys® proBNP Immunoassay

Indications For Use:

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys family of analyzers.

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Cooper

(Division Sign-Off)
Division of Clinical Laboratory Levices
510(k) Number K022516

Regulation Number and Section

§ 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.”