StatusFirst™ CHF (Congestive Heart Failure) NT-proBNP is a rapid test for the in vitro quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in human EDTA plasma. The device is intended for use with the DXpress™ Reader to provide quantitative results as an aid in the diagnosis of CHF.

Device Description

The StatusFirst™ CHF NT-proBNP test device utilizes biotin coupled anti-NTproBNP antibody/streptavidin solid-phase chromatographic immunoassay technology to quantitatively determine the concentration of NT-proBNP in human EDTA plasma. After a sample has been dispensed into the sample well, the StatusFirst™ CHF NTproBNP test device is placed in the DXpress™ Reader. The DXpress™ Reader displays the NT-proBNP concentration 15 minutes after sample addition. The DXpress™ Reader is programmed to automatically convert the intensity of the test band (as indicated by the "pBNP" line on the test device) into a concentration of NTproBNP by using lot specific calibration factors supplied with each box of 20 StatusFirst™ CHF NT-proBNP test devices. The NT-proBNP concentration in the sample correlates with the intensity of the test band.

AI/ML Overview

The provided document describes a 510(k) premarket submission for the StatusFirst™ CHF NT-proBNP device, which measures NT-proBNP levels for aid in CHF diagnosis. The study described is a method comparison study intended to demonstrate substantial equivalence to a predicate device, the Roche Elecsys® proBNP Immunoassay.

Here's an analysis of the provided information according to your requested categories:

Acceptance Criteria and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a pass/fail format with specific thresholds. Instead, it presents the results of a method comparison study against a predicate device, aiming to demonstrate substantial equivalence. The "reported device performance" is primarily shown through the correlation between the StatusFirst™ device and the predicate.

Acceptance Criteria (Implied by Substantial Equivalence to Predicate)	Reported Device Performance (StatusFirst™ CHF NT-proBNP vs. Elecsys® proBNP)
Good correlation for CHF subjects (compared to predicate)	Spearman Rank correlation: 0.922 (n = 324)
Good correlation for non-CHF subjects (compared to predicate)	Spearman Rank correlation: 0.948 (n = 324)
Good correlation for all subjects combined (compared to predicate)	Spearman Rank correlation: 0.973 (n = 648)
Agreement in measuring range (though predicate has wider range, the functional range of the new device should be clinically useful and comparable)	StatusFirst™ Measuring Range: 20-5,000 pg/mL Elecsys® proBNP Measuring Range: 5-35,000 pg/mL (StatusFirst™ falls within a relevant clinical range)
Functional Sensitivity (comparable to predicate)	StatusFirst™ Functional Sensitivity: 20 pg/mL Elecsys® proBNP Functional Sensitivity: < 50 pg/mL (StatusFirst™ is superior or equal)
Limit of Detection (comparable to predicate)	StatusFirst™ Limit of Detection: 20 pg/mL Elecsys® proBNP Limit of Detection: 5 pg/mL (Predicate is more sensitive, but StatusFirst's LOD is within a clinically relevant range)
Precision (acceptable CV values)	StatusFirst™ Precision: Within run: 11.1-16.8%CV Total: 12.4-18.1%CV (at various concentrations) Elecsys® proBNP Precision: E170 Within run: 0.9-1.1%CV; E170 Total: 3.7-5.8%CV E1010/2010 Within run: 1.8-2.7%CV; E1010/2010 Total: 2.3-3.2%CV (StatusFirst™ shows higher CVs than predicate)
Minimal interference from common substances/drugs	StatusFirst™ Limitations: No interference from bilirubin (10.0 mg/dL), hemoglobin (100 mg/dL), triglycerides (1500 mg/dL), d-biotin (100 ng/mL), rheumatoid factors (2030 IU/mL), creatinine (20 µg/mL), human albumin (16 g/dL), 63 common pharmaceuticals.

The study "proves" the device meets acceptance criteria by demonstrating good correlation and comparable performance characteristics to the legally marketed predicate device, forming the basis for the FDA's determination of substantial equivalence. The provided data suggests that while some performance metrics (like precision and limit of detection) differ, the overall performance, particularly the strong correlation, supports this claim.

2. Sample size used for the test set and the data provenance

Sample Size for Test Set:
- CHF subjects: 355
- Non-CHF subjects: 333 (282 apparently healthy, 51 with diabetes, renal insufficiency, hypertension or chronic obstructive pulmonary disease)
- Total for correlation analysis (after exclusion): 648 (324 CHF + 324 non-CHF) – Note: the document states N=324 for CHF and N=324 for non-CHF for Spearman Rank correlation, implying some samples were out of range or excluded from this specific calculation.
Data Provenance: The document does not explicitly state the country of origin. The study is retrospective as it involves "patient samples" that were measured with both devices, implying existing samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. This study is a method comparison of a diagnostic test (NT-proBNP measurement) against a predicate device, not an interpretation of images or clinical data by experts to establish a "ground truth" diagnosis. The "truth" for this study is the measurement obtained by the predicate device. The classification of subjects as "CHF subjects" and "non-CHF subjects" would have been based on clinical diagnoses, but the process of how these initial diagnoses were established is not detailed in this submission.

4. Adjudication method for the test set

Not applicable. As noted above, this is a method comparison study for an in vitro diagnostic device, not a study where human interpretation of data requires adjudication. The comparison is between quantitative results produced by two different instruments.

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

Not applicable. This is not an AI-based device or an imaging interpretation study involving human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in a sense. The StatusFirst™ CHF NT-proBNP device is an in vitro diagnostic (IVD) test system. Its standalone performance refers to its ability to accurately measure NT-proBNP concentrations. The method comparison study directly evaluates this "standalone" performance by comparing its quantitative results against a predicate IVD device, independent of human interpretation or intervention in the measurement process itself, other than operating the device. The DXpress™ Reader automatically converts the test band intensity to a concentration.

7. The type of ground truth used

The "ground truth" for this method comparison study is the quantitative NT-proBNP concentration obtained from the Roche Elecsys® proBNP Immunoassay, which is the legally marketed predicate device. The study aims to show that the new device's measurements are highly correlated with and similar to those of the predicate.

8. The sample size for the training set

Not applicable. This medical device (immunoassay) is not based on a machine learning algorithm that requires a "training set" in the conventional sense. The device's calibration refers to internal manufacturer processes using clinical calibrators and a 5-parameter logistic curve fit, but this isn't analogous to training data for an AI model.

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" as understood in machine learning. The calibration data used by the manufacturer is based on "clinical calibrators" and internal procedures, designed to accurately reflect NT-proBNP concentrations.

Summary

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MAR 1 3 2006

StatusFirst™ CHF NT-proBNP and DXpress™ Reader system 510(k) Premarket Submission K051596

Summary of Safety and Effectiveness of StatusFirst™ CHF NT-proBNP

This 510(k) summary of safety and effectiveness is submitted in accordance with the requirements of 21 CFR Sec. 807.92.

Submitter's Name	Nanogen Inc.
Address	10398 Pacific Center CourtSan Diego, California 92121
Phone Number	858-410-4877
Contact Person	Van N. SchrammVice President, Regulatory Affairs and QualityAssurance
Date of OriginalPreparation	June 13, 2005
Date of Response toRequest for AdditionalInformation	March 6, 2006
Device Names	Trade Name: StatusFirst™ CHF NT-proBNPCommon Name: Immunoassay for the quantitativedetermination of NT-proBNP in human EDTA plasmaClassification Name: B-Type Natriuretic Peptide Testsystem (21 CFR 862.1117, product code NBC)
Predicate Device	Roche's Elecsys® pro-BNP ImmunoassayK032646
Intended Use	StatusFirstTM CHF (Congestive Heart Failure) NT-proBNP is a rapid test for the in vitro quantitativedetermination of N-terminal pro-Brain natriuretic peptide(NT-proBNP) in human EDTA plasma. The device isintended for use with the DXpress™ Reader to providequantitative results as an aid in the diagnosis of CHF.

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Device Description

Comparison to Predicate

A method comparison was performed using a total of 355 CHF subjects and 333 non-CHF subjects. The non-CHF subjects include 282 apparently healthy subjects and 51 subjects with diabetes, renal insufficiency, hypertension or chronic obstructive pulmonary disease.

NT-proBNP levels from the above patient samples were measured with both the StatusFirst™ CHF NT-proBNP test in conjunction with the DXpress™ Reader, and the Roche Elecsys® proBNP immunoassay on the Roche Elecsys® 2010 immunoassay analyzer. Results within the measuring range of the StatusFirst™ CHF NT-proBNP test (20-5,000 pg/mL) were analyzed using Passing-Bablok regression.

a. CHF subjects

StatusFirst™ CHF NT-proBNP = 50.2 pg/mL+0.899* Elecsys® proBNP 95% confidence interval for intercept = [18.3, 74.0] 95% confidence interval for slope = [0.868, 0.939] Spearman Rank correlation was calculated as 0.922 with n = 324

b. Non-CHF subjects

StatusFirst™ CHF NT-proBNP = 5.0 pg/mL+1.022* Elecsys® proBNP 95% confidence interval for intercept = [0.3206, 9.4558] 95% confidence interval for slope = [0.9648, 1.0913] Spearman Rank correlation was calculated as 0.948 with n = 324

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c. All subjects

StatusFirst™ CHF NT-proBNP = 9.4 pg/mL+0.956* Elecsys® proBNP 95% confidence interval for intercept = [5.1, 12.6] 95% confidence interval for slope = [0.934, 0.981] Spearman Rank correlation was calculated as 0.973 with n = 648

The table below compares the StatusFirst™ CHF NT-proBNP test to the predicate device.

Feature	StatusFirst™ CHF NT-proBNP	Elecsys® proBNP
510(k) number	K051596	K032646
Intended Use	Immunoassay for the in vitroquantitative determination of N-terminal pro-Brain natriureticpeptide in human EDTA plasma	Immunoassay for the in vitroquantitative determination of N-terminal pro-Brain natriureticpeptide in human serum andplasma
Indication for Use	StatusFirst™ CHF NT-proBNP isa rapid test used for thequantitative determination of N-terminal pro-Brain natriureticpeptide (NT-proBNP) in humanEDTA plasma.The device is intended to be usedwith the DXpress™ Reader toprovide quantitative results as anaid in the diagnosis of CHF.	Elecsys® proBNP is used as an aidin the diagnosis of individualssuspected of having congestiveheart failure.The test is further indicated for therisk stratification of patients withacute coronary syndrome andcongestive heart failure.
Assay Protocol (Type)	Chromatographic Immunoassay	ElectrochemiluminescenceImmunoassay
Reference	Roche Elecsys® proBNP assay	Roche purified synthetic NT-proBNP
Calibration Interval	Calibration of each specific lot isperformed by the manufacturerusing clinical calibrators andemploying a 5-parameter logisticcurve fit. For each new lot, theend-user needs only transfercalibration information to thereader(s) from the lot-specific datachip provided. Once transferred (aone-time only requirement), thecalibration information is gooduntil the expiration date of theStatusFirst™ CHF NT-proBNPtest device.	E170/E2010• After 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)
Feature	StatusFirst™ CHF NT-proBNP	Elecsys® proBNP
510(k) number	K051596	K032646
Sample Type	Human EDTA plasma	Human serum and plasma
Reagent Stability	Unopened	Unopened
	Up to stated expirationdate when stored at 2-8°CStable for 14 days whenstored at 18-30°C,provided the expirationdate printed on the pouchis not exceeded	Up to stated expirationdate when stored at 2-8°COpened12 weeks at 2-8°C8 weeks on E1708 weeks on E20104 weeks on E1010 (20-25°C ambient temp - upto 20 hours opened intotal)
Calibrator	Electronic code chip	Elecsys® proBNP CalSet
Controls	Commercially available proBNPcontrols	Elecsys® PreciControl proBNP
Result Interpretation (Cut-off)	125 pg/mL for patients youngerthan 75 years and 450 pg/mL forpatients 75 years and older	125 pg/mL for patients youngerthan 75 years and 450 pg/ml forpatients 75 years and older
Instrument	DXpress™ Reader	Elecsys 1010, Elecsys 2010 andMODULAR analytics E170 familyof analyzers
Measuring Range	20-5,000 pg/mL	5-35,000 pg/mL
Antibody	Monoclonal (mouse) antibody andPolyclonal (goat) antibody	Polyclonal (sheep) antibody
Sample Volume	3 drops using dropper providedwith test device	20 µL
Precision	Within run11.1%CV @ 64.9 pg/mL12.8%CV @ 103.5 pg/mL13.1%CV @ 375.5 pg/mL16.8%CV @ 2145.8 pg/mLTotal12.4%CV @ 64.9 pg/mL13.7%CV @ 103.5 pg/mL13.9%CV @ 375.5 pg/mL18.1%CV @2145.8 pg/mL	E170 - 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 @ 355pg/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/mL
Hook Effect	No effect up to 300,000 pg/mL	No effect up to 300,000 pg/mL
Functional Sensitivity	20 pg/mL	< 50 pg/mL
Limit of Detection	20 pg/mL	5 pg/mL
Specificity	No substance demonstrated	The pharmaceutical Natrecor®
Feature	StatusFirst™ CHF NT-proBNP	Elecsys® proBNP
510(k) number	K051596	K032646
	significant cross-reactivity(% cross-reactivity < 0.1%)	shows no significant cross-reactivity at 300 pg/mL and 3,000pg/mL NT-proBNP; sixteen othersubstances also show nosignificant cross reactivity.
Limitations	No interference frombilirubin up to 10.0 mg/dL No interference fromhemoglobin up to 100 mg/dL No interference fromtriglycerides up to 1500mg/dL No interference with d-biotin up to 100 ng/mL In patients receiving highbiotin doses (5mg/day),samples may be used withoutthe need to wait forclearance of potentiallycirculating biotin No interference observedfrom rheumatoid factors upto 2030 IU/mL No interference withcreatinine up to 20 µg/mL No interference from highlevels of human albumin (upto 16 g/dL)	No interference frombilirubin up to 35 mg/dL No interference fromhemoglobin up to 1400mg/dL No interference fromtriglycerides up to 4000mg/dL No interference withbiotin up to 30 ng/mL In patients receiving highbiotin doses > 5 mg/dL,sample should not be takenuntil 8 hours afteradministration No interference fromrheumatoid factor up to 1500IU/mL
	No interference with 63commonly usedpharmaceuticals	Rare occurrence ofinterference from high tiers ofanti-streptavidin andruthenium No interference with 51commonly usedpharmaceuticals
	Use in conjunction withpatient medical history,clinical exam and otherfindings	Use in conjunction withpatient medical history,clinical exam and otherfindings

Comparison to Predicate

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StatusFirst™ CHF NT-proBNP 510(k) Premarket Submission K021296

Comments and conclusion on Substantial Equivalence

The StatusFirst™ CHF NT-proBNP and the Elecsys® proBNP assays are both intended for the in vitro quantitative determination of NT-proBNP. Both tests are indicated for use as an aid in the diagnosis of Congestive Heart Failure.

Good correlation has been demonstrated between the StatusFirst™ CHF NT-proBNP and the Elecsys® proBNP assays.

StatusFirst™ CHF NT-proBNP and the Elecsys® proBNP devices are substantially equivalent based upon their intended use and performance characteristics.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/6/Picture/2 description: The image shows a seal for the Department of Health & Human Services Utah. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES UTAH" around the perimeter. In the center of the seal is a stylized image of a person with their arms outstretched.

MAR 1 3 2006

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Van N. Schramm Vice President, Quality Assurance and Regulatory Affairs Nanogen, Inc. 10398 Pacific Center Court San Diego, CA 92121

Re: K051596

Trade/Device Name: StatusFirst™ CHF NT-proBNP Regulation Number: 21 CFR§862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: February 17, 2006 Received: February 21, 2006

Dear Ms. Schramm:

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. Iisting 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 G

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): K051596

Device Name: StatusFirst™ CHF NT-proBNP

Indications for Use: StatusFirst™ CHF (Congestive Heart Failure) NT-proBNP is a rapid test for the in-vitro quantitative determination of N-terminal pro-Brain natriuretic peptide (NT-proBNP) in human EDTA plasma. The device is intended for use with the DXpress™ Reader to provide quantitative results as an aid in the diagnosis of CHF.

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 IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson
Division Sign-Off

Office of In Vitro Diagnos Device Evaluation and S

510(k) K051596

Page 1 of 1

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.”