SENTINEL AMMONIA ULTRA DIAGNOSTIC ASSAY

K051114 · Sentinel Ch. Srl · JIF · Nov 25, 2005 · Clinical Chemistry

Device Facts

• Record ID: K051114
• Device Name: SENTINEL AMMONIA ULTRA DIAGNOSTIC ASSAY
• Applicant: Sentinel Ch. Srl
• Product Code: JIF · Clinical Chemistry
• Decision Date: Nov 25, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1065
• Device Class: Class 1

Intended Use

The Ammonia Ultra is intended for the in vitro quantitative determination of Ammonia (NH3) in human plasma. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye’s syndrome. The Ammonia Controls are intended as a means of monitoring Sentinel Ammonia Ultra Assay.

Device Story

Sentinel Ammonia Ultra is an enzymatic in vitro diagnostic assay for quantitative ammonia determination in human plasma. Input: human plasma sample. Principle: ammonia reacts with alpha-ketoglutarate and NADH in the presence of glutamate dehydrogenase (GLDH) to yield glutamate and NAD+; lactate dehydrogenase (LDH) is included to reduce endogenous pyruvate interference. Output: ammonia concentration calculated by multiplying the rate of absorbance decrease at 340 nm by a calibration factor derived from a 500 µg/dL aqueous standard. Used in clinical chemistry laboratories on automated analyzers; operated by laboratory professionals. Results assist clinicians in diagnosing and monitoring severe liver disorders like cirrhosis, hepatitis, and Reye's syndrome. Performance is verified using liquid bovine albumin-based controls at three levels.

Clinical Evidence

Performance evaluations included sensitivity, intra-assay imprecision, inter-assay imprecision, and method comparison. No specific clinical trial data or statistical metrics (e.g., AUC, p-values) provided in the summary.

Technological Characteristics

Enzymatic spectrophotometric assay. Reagents: alpha-ketoglutarate, glutamate dehydrogenase, NADH, lactate dehydrogenase. Detection: 340 nm absorbance. Form factor: liquid reagent/calibrator/control kit. Connectivity: integrated with Abbott ARCHITECT c8000 analyzer. Shelf life: 18 months at room temperature. Standards: CLSI EP05-A2, EP06-A, EP09-A2.

Indications for Use

Indicated for in vitro quantitative determination of ammonia in human plasma for patients with suspected or diagnosed severe liver disorders, including cirrhosis, hepatitis, and Reye's syndrome. For professional use only.

Regulatory Classification

Identification

An ammonia test system is a device intended to measure ammonia levels in blood, serum, and plasma, Ammonia measurements are used in the diagnosis and treatment of severe liver disorders, such as cirrhosis, hepatitis, and Reye's syndrome.

Predicate Devices

• Ammonia-Incorporating Dynamic Stabilization Technology (k974620)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the word "SENTINEL" in large, bold, black letters. Below the word "SENTINEL" is the word "DIAGNOSTICS" in smaller, thinner letters. The letters in "DIAGNOSTICS" are also black, but they are not as bold as the letters in "SENTINEL".

Kosm14

# NOV 2 5 2005

# 510k Summary Sentinel Ammonia Ultra Diagnostic Assay

K Number:

| 1. Submitter's information: | Dr. Ugo De Luca<br>Managing Director<br>Sentinel CH Srl<br>Via Principe Eugenio<br>20155 Milan, Italy<br>Tel.: [phone]<br>Fax: [phone]<br>e-mail: [e-mail] |
|-----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2. Contact person: | Mr. Davide Spada<br>Application Specialist<br>Sentinel CH Srl<br>Via Principe Eugenio<br>20155 Milan, Italy<br>Tel.: [phone]<br>Fax: [phone]<br>e-mail: [e-mail] |
| 3. Date summary prepared: | 16 November 2005 |

#### Device name and classification 4.

The Sentinel Ammonia Ultra Diagnostic Assay described in this 510(k) consists of reagent and controls, packaged and distributed in two kits, but together making up the Ammonia assay. The device is intended to be sold as an in-vitro test for professional use.

Product name and classification information are provided in Table 4.1 below.

| Trade/Device Name | Regulation name | Classification<br>panel | Regulatory<br>class | Product<br>Code |
|-------------------|-----------------|-------------------------|---------------------|-----------------|
|-------------------|-----------------|-------------------------|---------------------|-----------------|

| Trade/Device Name | Regulation name | Classification panel | Regulatory class | Product Code |
|-------------------|----------------------------------------------------------------------|-----------------------|------------------|--------------|
| Ammonia Ultra | Enzymatic Method,<br>Ammonia | Clinical<br>Chemistry | I | JIF |
| Ammonia Control | Single (Specified)<br>Analyte Controls<br>(Assayed and<br>Unassayed) | Clinical<br>Chemistry | I | JJX |

Page 62 of 74

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image shows the logo for Sentinel Diagnostics. The logo is made up of two words, "SENTINEL" and "DIAGNOSTICS", stacked on top of each other. The word "SENTINEL" is in a larger, bolder font than the word "DIAGNOSTICS".

### Device description 5.

The Sentinel Ammonia Ultra Diagnostic Assay described in this 510(k) submission is composed by reagent, calibrator and controls, packaged and distributed in different kits. The device is intended to be sold as an in-vitro test for professional use.

The Ammonia Ultra is an enzymatic in vitro diagnostic assay for the quantitative determination of ammonia in human plasma. Ammonia, in the presence of glutamate dehydrogenase (GLDH), combines with α-ketoglutarate and NADH to yield glutamate and NAD*. The decrease in absorbance due to the NADH oxidation, at 340 nm, is proportional to the ammonia concentration in the examined plasma. The reagent contains lactate dehydrogenase (LDH) in excess, to rapidly reduce endogenous pyruvate so that it does not interfere with the assay system. The actual concentration of ammonia is determined multiplying the rate of absorbace per the calibration factor obtained during the calibration with the ammonia standard of 500 µg/dL included in the kit.

To ensure a correct determination during quantification of ammonia samples, a quality control procedure is required. The Ammonia Controls are liquid controls at 3 levels, prepared in bovine albumin matrix, and are used to verify the performance of the Ammonia Ultra assay. The value and range assigned to each level is specific for each lot and has been determined in rigorously standardized condition by the calculation of the median obtained in multiple determinations using reagents and standard relative to the Ammonia Ultra.

#### Intended Use 6.

The Ammonia Ultra is intended for the in vitro quantitative determination of Ammonia (NH3) in human plasma on automated system.

Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome" CFR 862.1065

The Ammonia Controls are intended as a means of monitoring Sentinel Ammonia Ultra assay method.

### Comparison with Predicate Devices 7.

Table 7.1 below provides a list of predicate devices for the Sentinel Ammonia Ultra Diagnostic Assay devices.

| # | Sentinel Trade Device Name | Predicate Device Name | Predicate Device Manufacturer | Predicate device (k) | FDA clearance date |
|---|----------------------------|---------------------------------------------------------------------|-------------------------------|----------------------|--------------------|
| 1 | Ammonia Ultra | Ammonia-<br>Incorporating<br>Dynamic<br>Stabilization<br>Technology | Trace America, Inc | K974620 | 02 Jan. 1998 |
| 2 | Ammonia Controls | Quantimetrix<br>Ammonia Controls | Quantimetrix Corp. | K913346 | 25 Sep. 1991 |

# Table 7.1 Predicate devices for Sentinel Ammonia Ultra Diagnostic Assay devices

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the logo for Sentinel Diagnostics. The word "SENTINEL" is in large, bold, black letters. Below that, in smaller letters, is the word "DIAGNOSTICS".

The Sentinel's Ammonia reagent and controls and the predicate devices are both used for the determination of ammonia. In addition, they use the same:

- Sample type: plasma .
- Technology: enzymatic .
- Detection method: NADH oxidation .
- Calibration: against aqueous standard .

However, Ammonia Ultra will be used with the Abbott ARCHITECT® c8000" analyzer, r over the Trace Ammonia labeling indicates that the product can be used with any automated clinical chemistry analyzer.

#### Performance Data 8.

Performance evaluations included sensitivity, intra- and inter-assay imprecision, and method comparison.

#### Conclusion 9.

The performance and safety data presented in this premarket notification support a finding of substantial equivalence between the Sentinel Ammonia Ultra Diagnostic Assay and the predicate devices specified in this submission.

Appendix E

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized depiction of an eagle with three tail feathers, representing the department's mission to protect the health of all Americans and provide essential human services. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 2 5 2005

Mr. Davide Spada Application Specialist Sentinel CH. S.r.l. Via Principe Eugenio, 5 20155 Milan, Italy

k051114 Re:

Trade/Device Name: Sentinel Ammonia Ultra Regulation Number: 21 CFR 862.1065 Regulation Name: Ammonia test system Regulatory Class: Class I Product Code: JIF, JJX Dated: September 26, 2005 Received: November 8, 2005

Dear Mr. Spada:

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 bublish 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).

{4}------------------------------------------------

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) I mis letter will and in your a substantial equivalence of your device to a legally premiuted 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 [phone]. 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 I ou may of and Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto
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

{5}------------------------------------------------

510(k) Number (if known): _ KOSIIIIY

Sentinel Ammonia Ultra Device Name:

Indications For Use:

The Ammonia Ultra is intended for the in vitro quantitative determination of Ammonia (NH3) in human plasma.

Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome

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 Benam
Division Sign Off

Division Sian-C

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K051114

Page I of 7 -

{6}------------------------------------------------

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: _________________________________________________________________________________________________________________________________________________________________

Indications For Use:

The Ammonia Controls are intended as a means of monitoring Sentinel Ammonia Ultra assay method.

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 Buneen
Division Sign-Off

Office of in Vitro Diagnostic Device Evaluation and Safety

Page Lof 2 -

510(k) K051114