VITROS Immunodiagnostics NT-proBNP Reagent Pack: For the in vitro quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (EDTA or heparin) to aid in the diagnosis of congestive heart failure and for the risk stratification of acute coronary syndrome and congestive heart failure. The test is further indicated 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 test can also be used in the assessment of heart failure severity in patients diagnosed with congestive heart failure.

VITROS Immunodiagnostic Products NT-proBNP Calibrator For in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (EDTA or heparin).

VITROS Immunodiagnostic Products NT-proBNP Range Verifiers For the in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP).

Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of there main elements: The VITROS Immunodiagnostic Products range of immunoassay products in this case the VITROS Immunodiagnostic Products NTproBNP Reagent Pack, the VITROS Immunodiagnostic Products NT-proBNP Calibrators, and the VITROS Immunodiagnostic Products NT-proBNP Range Verifiers (which are combined by the VITROS Immunodiagnostic system to perform the VITROS NTproBNP assay) and VITROS Immunodiagnostic Products High Sample Diluent B. The VITROS Immunodiagnostic System -- instrumentation, which provides automated use of the immunoassay kits. Common reagents used by the VITROS System in each assay.

AI/ML Overview

The provided document is a 510(k) summary for the VITROS Immunodiagnostic Products NT-proBNP Reagent Pack, Calibrator, and Range Verifier. This type of regulatory submission focuses on demonstrating substantial equivalence to a predicate device rather than providing detailed acceptance criteria and study results for novel device performance.

Therefore, the document does not contain the specific information requested regarding acceptance criteria and a study proving the device meets those criteria in the typical format of a clinical performance study for an AI-powered device. Instead, it relies on demonstrating comparable performance to an already cleared predicate device.

Here's a breakdown of why the requested information cannot be fully provided from this document:

No explicit acceptance criteria or performance study for device novelty: Since this is a substantial equivalence submission for an in vitro diagnostic (IVD) device, the "acceptance criteria" are implicitly met by demonstrating that the new device's performance characteristics (e.g., measuring range, analytical sensitivity, functional sensitivity, intended use) are substantially equivalent to a legally marketed predicate device. There isn't an independent study outlined to "prove" the device meets specific (novel) acceptance criteria, but rather a comparison to an established device.
No AI component: This device is an immunoassay system for measuring NT-proBNP, not an AI-powered diagnostic tool. Therefore, questions related to AI-specific elements (like test sets, training sets, adjudication, MRMC studies, or standalone algorithm performance) are not applicable.

Despite these limitations, I can extract and infer some information based on the comparison tables provided.

Inferred Acceptance Criteria and Reported Device Performance (Based on Predicate Device Comparison)

The acceptance criteria for this device are implicitly tied to demonstrating performance comparable to the predicate device (Roche Elecsys proBNP Immunoassay K051382 for the Reagent Pack and Calibrator, and VITROS Immunodiagnostic Products CEA Range Verifiers K990984 for the Range Verifiers).

Acceptance Criteria (Inferred from Predicate Equivalence)	Target/Predicate Performance (Roche Elecsys proBNP Immunoassay K051382)	Reported Device Performance (VITROS NT-proBNP Reagent Pack)
Intended Use	Aid in diagnosis of CHF, risk stratification for ACS/CHF, assessment of increased risk of cardiovascular events/mortality in stable CAD, assessment of HF severity.	Substantially similar Intended Use.
Basic principle	Electrochemiluminescence Immunoassay	Chemiluminescence Immunoassay
Antibody	Biotinylated polyclonal anti-NT-proBNP (sheep)	Biotinylated polyclonal anti-NT-proBNP (sheep)
Instrumentation	Elecsys family of analyzers (1010, 2010, Modular Analytics)	ECI/ECIQ Immunodiagnostic System
Sample type	Human serum and plasma	Human serum and plasma (EDTA and heparin)
Expected Values	Age and sex-related statistics. Cut-offs: <75 years: 125 pg/mL, >=75 years: 450 pg/mL.	Substantially similar.
Measuring Range	5-35,000 pg/mL	5.00-35,000 pg/mL
Hook Effect	No high dose hook effect up to 300,000 pg/mL	No high dose hook effect up to 500,000 pg/mL
Analytical Sensitivity	5 pg/mL	< 5.00 pg/mL
Functional Sensitivity	< 50 pg/mL	< 10.0 pg/mL

Regarding the specific questions:

A table of acceptance criteria and the reported device performance:
- See the table above. These are inferred acceptance criteria based on the characteristics of the predicate device that the new device aims to be equivalent to. The "reported device performance" is the claim made by the new device.
Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- This information is not provided in a 510(k) summary for an IVD device of this type. The summary focuses on comparing technical and performance characteristics, not on a detailed clinical study with a "test set" in the context of an AI device.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
- Not applicable, as this is an immunoassay, not an AI device requiring expert ground truth in this manner.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable, as this is an immunoassay, not an AI device using adjudication methods for a test set.
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, as this is an immunoassay, not an AI device involving human readers or MRMC studies.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable, as this is an immunoassay, not an AI algorithm. The device functions as a standalone quantitative measurement system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For an immunoassay, "ground truth" typically refers to established analytical reference methods or reference materials. The document implies that the "truth" for the new device's measurements is established by its demonstrated correlation or equivalence to the predicate device's measurements, which are already accepted. For calibrators, the "levels" are specific pg/mL concentrations (e.g., Cal 1 0 pg/mL, Cal 2 150 pg/mL).
The sample size for the training set:
- Not applicable, as this is an immunoassay. The concept of a "training set" is relevant for machine learning algorithms, which are not involved here. Assay development involves method optimization and validation, not model training.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the AI sense for this immunoassay.

Summary

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JUN -6 2006

Image /page/0/Picture/2 description: The image shows the logo for Ortho-Clinical Diagnostics, which is identified as a Johnson & Johnson company. Below the logo is the address "100 Indigo Creek Drive, Rochester, New York 14626-5101". The logo is in black and white.

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:

1 Submitter Name, Address and Contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (585) 453-4131

Contact Person: Leah Van De Water

2 Preparation Date

Date 510(k) prepared: March 8, 2006

3 Device Name

VITROS Immunodiagnostic Products NT-proBNP Reagent Pack Common Name: NT-proBNP Reagent Pack Classification Name: B-Type natriuretic peptide test system (862.1117), Class II
VITROS Immunodiagnostic Products NT-proBNP Calibrators Common Name: NT-proBNP Calibrators Classification Name: Calibrator (862.1150), Class II
VITROS Immunodiagnostic Products NT-proBNP Range Verifiers Common Name: NT-proBNP Range Verifiers Classification: Quality control material (862.1660), Class I

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4 Predicate Device

The VITROS Immunodiagnostic Products NT-proBNP Reagent Pack . VITROS Immunodiagnostic Product NT-proBNP Calibrators are substantially equivalent to the Roche Elecsys® proBNP Immunoassay K051382.

The VITROS Immunodiagnostic Products NT-proBNP Range Verifiers are substantially equivalent to the VITROS Immunodiagnostic Product CEA Range Verifiers previously cleared under K990984.

5 Device Description

The system is comprised of there main elements:

. The VITROS Immunodiagnostic Products range of immunoassay products in this case the VITROS Immunodiagnostic Products NTproBNP Reagent Pack, the VITROS Immunodiagnostic Products NT-proBNP Calibrators, and the VITROS Immunodiagnostic Products NT-proBNP Range Verifiers (which are combined by the VITROS Immunodiagnostic system to perform the VITROS NTproBNP assay) and VITROS Immunodiagnostic Products High Sample Diluent B.
. The VITROS Immunodiagnostic System -- instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

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4.0: 510(k) Summary

Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total ß-hCG Reagent Pack and VITROS Immunodiagnostic Products Total ß-hCG Calibrators 510(k) premarket notification (K970894).

The VITROS System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

б Device Intended Use

VITROS Immunodiagnostics NT-proBNP Reagent Pack:

For the in vitro quantitative measurement of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) in human serum and plasma (EDTA or heparin) to aid in the diagnosis of congestive heart failure and for the risk stratification of acute coronary syndrome and congestive heart failure. The test is further indicated 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 test can also be used in the assessment of heart failure severity in patients diagnosed with congestive heart failure.

7 Comparison to Predicate Device

The VITROS Immunodiagnostic Products NT-proBNP Reagent Pack and Calibrators is substantially equivalent to the Roche Elecsys proBNP Immunoassay K051382. The VITROS Immunodiagnostic Products NT-proBNP Range Verifiers are substantially equivalent to the VITROS Immunodiagnostic Products CEA Range Verifiers K990984.

Tables 1 through 3 compare the VITROS Immunodiagnostic Products NTproBNP Reagent Pack, Calibrator and Range Verifier to the Roche Elecsys proBNP Immunoassay K051382 and VITROS Immunodiagnostic Products CEA Range Verifiers K990984.

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Table 1	Comparison of the VITROS ImmunodiagnosticProducts NT-proBNP Reagent Pack to the ElecsysproBNP Reagent Pack
---------	--------------------------------------------------------------------------------------------------------------------

ComparisonDeviceCharacteristic	VITROS(new device)	Elecsys(predicate device)
Intended Use	For the in vitroquantitativemeasurement of N-terminal pro BrainNatriuretic Peptide(NT-proBNP) inhuman serum andplasma (EDTA orheparin) to aid in thediagnosis ofcongestive heartfailure and for the riskstratification of acutecoronary syndromeand congestive heartfailure. The test isfurther indicated as anaid in the assessmentof increased risk ofcardiovascular eventsand mortality inpatients at risk forheart failure who havestable coronary arterydisease. The test canalso be used in theassessment of heartfailure severity inpatients diagnosedwith congestive heartfailure.	For the in vitro quantitativedetermination of N-terminal pro-Brain natriuretic peptide in humanserum and plasma. The ElecsysproBNP assay is used as an aid inthe diagnosis of individualssuspected of have congestive heartfailure. The test is furtherindicated for the risk stratificationsof patients with acute coronarysyndrome and 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.
Basic principle	ChemiluminescenceImmunoassay	ElectrochemiluminescenceImmunoassay
Antibody	Biotinylated polyclonalanti-NT-proBNP(sheep)	Biotinylated polyclonal anti-NT-proBNP (sheep)
Instrumentation	ECI/ECIQImmunodiagnosticSystem: Automatedanalyzer	Elecsys family of analyzers(Elecsys 1010, Elecsys 2010 andElecsys Modular AnalyticsImmunassay Analyzers
Sample type	Human serum andplasma (EDTA andheparin)	Human serum and plasma
Expected Values	Age and sex-related statistics Cut-offs of 125 pg/mL for patientsyounger than 75 years and 450pg/mL for patients75 years and older	Age and sex-related statistics Cut-offs of 125 pg/ml forpatients younger than 75 yearsand 450 pg/mL for patients 75years and older
Measuring Range	5.00-35,000 pg/mL	5-35,000 pg/mL
Hook Effect	No high dose hookeffect up to 500,000pg/mL	No high dose hook effect up to300,000 pg/mL
Analytical Sensitivity	< 5.00 pg/mL	5 pg/mL
Functional Sensitivity	< 10.0 pg/mL	< 50 pg/mL

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4.0: 510(k) Summary

. . . . . .

and the same of the same

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Comparison
DeviceCharacteristic	VITROS(new device)	Elecsys(predicate device)
Intended Use	For in vitro used in thecalibration of the VITROSImmunodiagnostic Systemfor the quantitativemeasurement of N-terminal pro BrainNatriuretic Peptide (NT-proBNP) in human serumand plasma (EDTA orheparin).	Elecsys proBNP Calset isused for calibrating thequantitative proBNP assayon the Elecsys 1010/2010and MODULARANALYTICS E170immunoassay systems
Matrix	Liquid; NT-proBNP inbuffer with bovine serumalbumin and antimicrobialagent	Lyophilized equine serummatrix with added syntheticNT-proBNP (1-76)
Levels	Cal 1 0 pg/mLCal 2 150 pg/mLCal 3 12,500 pg/mL	Cal 1 140 pg/mLCal 2 2700 pg/mL

Table 2 Comparison of the VITROS Immunodiagnostic Products NT-proBNP Calibrator to the Elecsys ® proBNP CalSet

Ortho-Clinical Diagnostics NT-proBNP 510(k)

ﺍﻟﻤﺴﺘﻮﻯ ﺍﻟﻤﺪﻳﺮ ﺍﻟﻤﺪﻳﻨﺔ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮ

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Comparison
DeviceCharacteristic	VITROS(new device)	VITROS(predicate device)
Intended Use	For in vitro use inverifying the calibrationrange of the VITROSImmunodiagnostic Systemwhen used for thequantitative measurementof N-terminal pro BrainNatriuretic Peptide (NT-proBNP)	For in vitro use in verifyingthe calibration range of theVITROS ImmunodiagnosticSystem when used for themeasurement of CEA.
Matrix	Liquid; Synthetic NT-proBNP in buffer withbovine serum albumin andantimicrobial agent	Liquid; Human CEA inbuffer with bovine serumalbumin and antimicrobialagent
Levels	Low and High	Low and High

Table 3 Comparison of the VITROS Immunodiagnostic Products NT-proBNP Range Verifiers to the VITROS Immunodiagnostic Products CEA Range Verifiers

10 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS NT-proBNP Reagent Pack, VITROS NTproBNP Calibrator and VITROS NT-proBNP Range Verifiers are safe and effective for the stated intended uses and is substantially equivalent to the cleared predicate devices.

The VITROS Immunodiagnostic Products NT-proBNP Reagent Pack and the VITROS Immunodiagnostic Products NT-proBNP Calibrator were compared to the Elecsys proBNP Immunoassay (K051382). The VITROS Immunodiagnostic Products NT-proBNP Range Verifiers were compared to the VITROS Immunodiagnostic Products CEA Range Verifiers.

Ortho-Clinical Diagnostics NT-proBNP 510(k)

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Image /page/7/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is in a bold, sans-serif font. The text is centered on the image and is the only element present. The background of the image is white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Leah Van De Water Regulatory Affairs Associate Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Dr. Rochester, NY 14626-5101

JUN - 6 2006

K060632 Re:

Trade/Device Name: VITROS Immunodiagnostic Products NT-proBNP Reagent Pack VITROS Immunodiagnostic Products NT-proBNP Calibrator VITROS Immunodiagnostic Products NT-proBNP Range Verifier Regulation Number: 21 CFR§ 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC, JIT, JJX Dated: May 5, 2006 Received: May 8, 2006

Dear Ms. Water:

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 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 (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 yours,

Alberto Garcia

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): ____________________________________________________________________________________________________________________________________________________

K060632

Device Name:

VITROS Immunodiagnostic Products NT-proBNP Reagent Pack VITROS Immunodiagnostic Products NT-proBNP Calibrator VITROS Immunodiagnostic Products NT-proBNP Range Verifier

Indications for Use:

VITROS Immunodiagnostics NT-proBNP Reagent Pack:

ﺮ ﺍ Prescription Use (Per 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 IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off	Page __ of __
Office of In Vitro Diagnostic DeviceEvaluation and Safety
(510(k)) K060632

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.”