Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay and analyzer, with no mention of AI or ML in the intended use, device description, or performance studies.

Therapeutic

No
The device is an in vitro diagnostic immunoassay that aids in diagnosis and risk stratification, but it does not directly treat or prevent disease.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the assay "is used as an aid in the diagnosis of individuals suspected of having congestive heart failure."

SaMD (Software as a Medical Device)

No

The device description explicitly states it is an immunoassay intended for use on a specific hardware analyzer (cobas e 601), and the performance studies are based on this hardware. It is a reagent/assay kit, not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The "Intended Use / Indications for Use" section explicitly states "Immunoassay for the in vitro quantitative determination of N-terminal pro-brain natriuretic peptide in human serum and plasma." The phrase "in vitro" is a key indicator of an IVD.
Sample Type: The test is performed on human serum and plasma, which are biological samples taken from the body but tested outside of it.
Purpose: The test is used as an aid in the diagnosis, risk stratification, and assessment of cardiovascular events, all of which are diagnostic purposes.
Device Description: The description details an "electrochemiluminescence immunoassay 'ECLIA'", which is a laboratory-based testing method.

All of these points align with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Immunoassay for the in vitro quantitative determination of N-terminal pro-brain natriuretic peptide in human serum and plasma. The Elecsys proBNP II STAT assay 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 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 cobas e 601 immunoassay analyzer.

Product codes

NBC, JIT

Device Description

Not Found

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies

Method Comparison: Both assays run on the cobas e 601, n = 120, Min = 5.10 pg/mL, Max = 30,583 pg/mL.
Passing/Bablok: Slope = 0.992, Intercept = -2.141, Tau/r/rho = 0.987.
Linear Regression: Slope = 0.986, Intercept = 13.964, Tau/r/rho = 0.998.
Deming Regression: Slope = 0.988, Intercept = 8.83, Tau/r/rho = 1.00.

Key Metrics

Measuring Range: 5-35,000 pg/mL
Precision (cobas e 601):
Within-run (Repeatability): 2.4% CV @ 130.0 pg/mL; 2.2% CV @ 4942.0 pg/mL; 3.5% CV @ 59.0 pg/mL; 2.0% CV @ 142.0 pg/mL; 1.8% CV @ 522.0 pg/mL; 1.9% CV @ 934.5 pg/mL; 2.0% CV @ 6552.0 pg/mL; 2.9% CV @ 30,870.0 pg/mL
Total (Intermediate): 2.5% CV @ 130.0 pg/mL; 2.6% CV @ 4942.0 pg/mL; 3.5% CV @ 59.0 pg/mL; 2.5% CV @ 142.0 pg/mL; 2.0% CV @ 522.0 pg/mL; 2.5% CV @ 934.5 pg/mL; 2.3% CV @ 6552.0 pg/mL; 5.4% CV @ 30,870.0 pg/mL
Analytical Sensitivity:
Limit of Blank (LoB): 5.00 pg/mL
Limit of Detection (LoD): 5.00 pg/mL
Functional Sensitivity: 50.00 pg/mL
Hook Effect: There is no high-dose hook effect at proBNP concentrations up to 300,000 pg/mL (300 ng/mL).
Limitations (unaffected by):
Hemoglobin ≤ 0.1 g/dL
Bilirubin up ≤ 25 mg/dL
Triglycerides ≤ 1,500 mg/dL
Biotin ≤ 30 ng/mL
Rheumatoid factors ≤ 1,500 IU/mL

Predicate Device(s)

K072437

Reference Device(s)

K022516

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.”

Summary

0

K0926649

Appendix | Updated 510(k) Summary

ستر،

FEB - 4 2010

Immunoassay Comparison
Feature	Predicate Device: Elecsys proBNP II Assay (K072437) (18 Minute)	Elecsys proBNP II STAT Assay
	General Assay Features
Intended
Use/
Indications
for Use	Immunoassay for the in vitro
quantitative determination of N-
terminal pro-brain natriuretic peptide
in human serum and plasma. The
Elecsys proBNP II assay 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 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 Elecsys and cobas e
immunoassay analyzers. | Same, except:
The assay name is changed:
... The Elecsys proBNP II STAT assa
is used as an aid in the diagnosis...

Elecsys instruments are removed:
The electrochemiluminescence
immunoassay "ECLIA" is intended
for use on the cobas e 601
immunoassay analyzer. |
| Assay
Protocol | Sandwich assay | Same |
| Detection
Protocol | Electrochemiluminescent
Immunoassay | Same |
| Application | 18 Minute | STAT (9 Minute) |
| Instrument
Platform | Roche Elecsys 2010/cobas e 411 and
MODULAR ANALYTICS
E170/cobas e 601 | cobas e 601 |
| Sample
Volume | 15 µL | Same |
| Immunoassay Comparison | | |
| Feature | Predicate Device: Elecsys proBNP
II Assay (K072437) (18 Minute) | Elecsys proBNP II STAT Assay |
| General Assay Features | | |
| Sample Type | Human serum and plasma treated with
K2-EDTA, K3-EDTA, lithium heparin
and Na-heparin plasma. | Same |
| Reagents | The proBNP II Assay is a sandwich
immunoassay with two antibodies
directed towards epitopes within the
N-terminal portion of the proBNP
molecule. The capture antibody is
biotinylated to react with streptavidin-
coated microparticles. The signal
antibody is tagged with ruthenium.
Both antibodies are monoclonal | Same antibodies and same epitopes |
| Traceability | The Elecsys proBNP II assay has been
standardized against the Elecsys
proBNP assay (K022516). This in turn
was standardized against reference
standards by weighing pure synthetic
NT-proBNP (1-76 amino acids) into
equine serum matrix. | Same |
| Calibrator | Elecsys proBNP II CalSet (K072437) | Elecsys proBNP II STAT CalSet will
have a different material number to
avoid confusion on instrument use.
The stability, value assignment and
matrix will be identical. |

1

2

	Immunoassay Comparison
Feature	Predicate Device: Elecsys proBNP
II Assay (K072437) (18 Minute)	Elecsys proBNP II STAT Assay
	General Assay Features
Calibration
Interval	Calibration must be performed once
per reagent lot using fresh reagent
(i.e. not more than 24 hours since the
reagent kit was registered on the
analyzer). Renewed calibration is
recommended as follows:

MODULAR ANALYTICS E170,
Elecsys 2010 and cobas e analyzers:
After 1 month (28 days) when
using the same reagent lotAfter 7 days (when using the
same reagent kit on the
analyzer)
Elecsys 1010 analyzer:
With every reagent kitAfter 7 days (ambient
temperature 20-25 °C)After 3 days (ambient
temperature 25-32 °C) | Calibration must be performed once
per reagent lot using fresh reagent (i.e.
not more than 24 hours since the
reagent kit was registered on the
analyzer). Renewed calibration is
recommended as follows:

cobas e 601:
After 1 month (28 days) when
using the same reagent lotAfter 7 days (when using the
same reagent kit on the
analyzer) |
| Controls | Elecsys PreciControl Cardiac II
(K072437) | Same |

3

Premarket Notification, 510(k) for Elecsys proBNP II

STAT Assay, Continued

Immunoassay Comparison
Feature	Predicate Device: Elecsys proBNP
II Assay (K072437) (18 Minute)	Elecsys proBNP II STAT Assay
General assay features
Traceability /
Standardization	This method has been standardized
against the Elecsys proBNP assay.
This in turn was standardized against
reference standards by weighing pure
synthetic NT-proBNP (1-76) into an
equine serum matrix.	Same
Reagent
Stability/
Storage	Store at 2-8 °C. Store the Elecsys
proBNP II reagent kit upright in order
to ensure complete availability of the
microparticles during automatic
mixing prior to use.

Stability:
Unopened at 2-8 °C—up to the stated
expiration date
After opening at 2-8 °C—12 weeks
On MODULAR ANALYTICS E170
and cobas e 601—8 weeks
On Elecsys2010 and cobas e 411—8
weeks | Same, but only reported on the cobas
e 601. |

4

Premarket Notification, 510(k) for Elecsys proBNP II

STAT Assay, Continued

	Immunoassay Comparison
Feature	Predicate Device: Elecsys proBNP
II Assay (K072437) (18 Minute)	Elecsys proBNP II STAT Assay
	Labeled Performance Characteristics
Measuring
Range	5-35,000 pg/mL	Same
Precision	Elecsys 1010/2010 and cobas e411 analyzers
Within-run (Repeatability)
4.2% CV @ 44.0 pg/mL
2.4% CV @ 126.0 pg/mL
1.3% CV @ 2410.0pg/mL
2.7% CV @ 33606.0 pg/mL
2.6% CV @ 82.0 pg/mL
1.2% CV @ 2318.0 pg/mL
Total (Intermediate)
4.6% CV @ 44.0 pg/mL
2.6% CV @ 126.0 pg/mL
1.8% CV @ 2410.0pg/mL
3.8% CV @ 33606.0 pg/mL
2.8% CV @ 82.0 pg/mL
1.6% CV @ 2318.0 pg/mL
MODULAR ANALYTICS E170 and cobas
e601:
Within-run (Repeatability)
1.9% CV @ 64.0 pg/mL
1.5% CV @ 124.0 pg/mL
1.3% CV @ 14142.0 pg/mL
1.8% CV @ 77.0 pg/mL
1.2% CV @ 2105.0 pg/mL
Total (Intermediate)
3.1% CV @ 46.0 pg/mL
2.7% CV @ 125.0 pg/mL
2.7% CV @ 32805.0 pg/mL
2.7% CV @ 77.0 pg/mL
2.7% CV @ 2170.0 pg/mL	cobas e 601:
Within-run (Repeatability)
2.4% CV @ 130.0 pg/mL
2.2% CV @ 4942.0 pg/mL
3.5% CV @ 59.0 pg/mL
2.0% CV @ 142.0 pg/mL
1.8% CV @ 522.0 pg/mL
1.9% CV @ 934.5 pg/mL
2.0% CV @ 6552.0 pg/mL
2.9% CV @ 30,870.0 pg/mL
Total (Intermediate)
2.5% CV @ 130.0 pg/mL
2.6% CV @ 4942.0 pg/mL
3.5% CV @ 59.0 pg/mL
2.5% CV @ 142.0 pg/mL
2.0% CV @ 522.0 pg/mL
2.5% CV @ 934.5 pg/mL
2.3% CV @ 6552.0 pg/mL
5.4% CV @ 30,870.0 pg/mL
Immunoassay Comparison
	Predicate Device: Elecsys proBNP
II Assay (K072437) (18 Minute)	Elecsys proBNP II STAT Assay
Feature	Labeled Performance Characteristics
Analytical
Sensitivity	Limit of Blank (LoB) not reported
Limit of Detection (LoD) 5.00 pg/mL
Limit of Quantitation (LoQ)
Functional Sensitivity: 50.00 pg/mL	Limit of Blank (LoB): 5.00 pg/mL
Limit of Detection (LoD): 5.00 pg/mL
Limit of Quantitation (LoQ)
Functional Sensitivity: 50.00 pg/mL
Hook Effect	There is no high-dose hook effect at
proBNP concentrations up to 300,000
pg/mL (300 ng/mL).	Same
Limitations	The assay is unaffected by:
• Hemoglobin ≤ 0.1 g/dL
• Bilirubin up ≤ 25 mg/dL
• Triglycerides ≤ 1,500 mg/dL
• Biotin ≤ 30 ng/mL
• Rheumatoid factors ≤ 1,500 IU/mL
In vitro tests were performed on 51
commonly used pharmaceuticals. No
interference with the assay was found.
• The risk of interference from potential
immunological interactions between
test components and rare sera has been
minimized by the inclusion of suitable
additives.
• As with all tests containing monoclonal
mouse antibodies, erroneous findings
may be obtained from samples taken
from patients who have been treated
with monoclonal mouse antibodies or
have received them for diagnostic
purposes.
• In rare cases, interference due to
extremely high titers of antibodies to
streptavidin and ruthenium can occur.
The test contains additives which
minimize these effects.
• For diagnostic purposes, the results
should always be assessed in
conjunction with the patient's medical
history, clinical examination and other
findings	Same

/

Continued on next page

।

5

Premarket Notification, 510(k) for Elecsys proBNP II

STAT Assay, Continued

6

Immunoassay Comparison
Feature	Predicate Device: Elecsys proBNP II Assay (K072437) (18 Minute)	Elecsys proBNP II-STAT Assay
Labeled Performance Characteristics
Method Comparison	Both assays run on the cobas e 601
	n = 120
Min = 5.10 pg/mL
Max = 30,583 pg/mL
	Passing/Bablok	Linear Regression	Deming Regression
	Slope	0.992	0.986	0.988
	Intercept	-2.141	13.964	8.83
	Tau/r/rho	0.987	0.998	1.00

7

CalSet Comparison
Feature	Predicate Device: Elecsys proBNP II CalSet (K072437)	Elecsys proBNP II STAT CalSet
Labeled Performance Characteristics
Intended Use	Elecsys proBNP II CalSet is used for calibrating the quantitative Elecsys proBNP II assay on Elecsys and cobas e immunoassay analyzers.	Elecsys proBNP II STAT CalSet is used for calibrating the quantitative Elecsys proBNP II STAT assay on the cobas e 601 immunoassay analyzer.
Levels	Two	Same
Format	Lyophilized equine serum	Same
Analyte
Concentration	Cal 1: ~140 pg/mL
Cal 2: ~2,700 pg/mL	Same
Handling	Dissolve carefully the contents of one bottle by adding exactly 1.0 mL of distilled water and allow to stand closed for 15 minutes to reconstitute. Mix carefully avoiding the formation of foam. Transfer the reconstituted calibrator into the empty, labeled snap-cap bottles supplied.	Same
Stability	Unopened:
• Store at 2 – 8°C until expiration date.
Reconstituted:
• 2 – 8°C: 2 weeks
• -20°C: 3 months (freeze only once)
• On Elecsys 1010/2010 and cobas e411 analyzers at 20 – 25°C: up to 5 hours
• On MODULAR ANALYTICS E170 and cobas e601 analyzers: use only once	Unopened:
• Store at 2 – 8°C until expiration date.
Reconstituted:
• 2 – 8°C: 2 weeks
• -20°C: 3 months (freeze only once)
• On the analyzer: use only once

8

Roche Diagnostics Corporation requests that the FDA not disclose the nature Confidentiality or existence of the premarket notification until the substantial equivalence decision has been reached.

Closing

We trust that the information provided in this Premarket Notification [Special 510(k)] will support a determination of substantial equivalence for the Elecsys proBNP II STAT Immunoassay.

If you should have questions or require further information, please do not hesitate to contact me.

Phone: (317) 521-3338
· FAX: (317) 521-2324
· jane.phillips(@roche.com

Sincerely,

Jane Phillips, PhD Regulatory Affairs Principal US Regulatory Submissions Roche Diagnostics Corporation

9

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/9/Picture/1 description: The image is a seal for the Department of Health & Human Services - USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of an eagle.

FEB - 4 2010

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Roche Diagnostics Corp. c/o Dr. Jane Phillips, Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250

Re: K092649 Trade Name: Elecsys proBNP II STAT Immunoassay, Elecsys proBNP II STAT CalSet Regulation Number: 21 CFR §862.1117 Regulation Name: B-type Natriuretic Peptide Test System Regulatory Class: Class II Product Codes: NBC, JIT Dated: January 4, 2010 Received: January 5, 2010

Dear Dr. Phillips:

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); medical device reporting (reporting of medical device-related adverse events) (21

10

Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Signature

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

11

Indications for Use Form

510(k) Number (if known):

Device Name: Elecsys proBNP II STAT Immunoassay

Immunoassay for the in vitro quantitative determination of N-terminal pro-brain natriuretic peptide in human serum and plasma. The Elecsys proBNP II STAT assay 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 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 cobas e 601 immunoassay analyzer.

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 OF NEEDED)

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

Carol Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K092649

Page 1 of 2

12

Indications for Use Form

510(k) Number (if known):

Device Name: Elecsys proBNP II STAT CalSet

Elecsys proBNP II STAT CalSet is used for calibrating the quantitative Elecsys proBNP II STAT assay on the cobas e 601 immunoassay analyzer.

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 OF NEEDED)

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

Carol Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K092649

· Page 2 of 2