(207 days)
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 method.
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 alpha-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 microgram/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.
This document describes the Sentinel Ammonia Ultra Diagnostic Assay, an in-vitro diagnostic device for the quantitative determination of ammonia in human plasma. The information provided in the 510(k) summary focuses on demonstrating substantial equivalence to predicate devices rather than detailing specific acceptance criteria and the comprehensive study results to prove device performance against those criteria. Therefore, several requested categories cannot be fully addressed from the provided text.
Here's the available information:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state pre-defined acceptance criteria with numerical targets. Instead, it mentions that "Performance evaluations included sensitivity, intra- and inter-assay imprecision, and method comparison." The conclusion states that "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." This implies that the performance measured for sensitivity, imprecision, and method comparison was deemed acceptable relative to the predicate devices. Without the full study report, specific acceptance criteria and detailed quantitative performance values are not available.
2. Sample sized used for the test set and the data provenance
The document does not specify the sample sizes used for sensitivity, intra- and inter-assay imprecision, or method comparison studies. It also does not provide information on the data provenance (e.g., country of origin, retrospective or prospective nature).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. The "ground truth" for an in-vitro diagnostic device like this would typically be established by a reference method or known concentrations of ammonia in control samples. Expert interpretation of results is usually less relevant than the analytical accuracy against a gold standard.
4. Adjudication method for the test set
This information is not provided. Adjudication methods are typically used in studies involving human interpretation or subjective assessments, which are not the primary focus for an enzymatic in-vitro diagnostic assay's performance evaluation.
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
An MRMC study is not applicable to this device. This is an in-vitro diagnostic assay for quantitative determination of ammonia, meaning there are no "human readers" or "AI assistance" involved in interpreting results in the way they would be in an imaging or diagnostic support system. Its performance is based on analytical accuracy.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This device is a standalone algorithm (an enzymatic assay, which functions like an algorithm in its chemical reactions and measurement). Its performance is inherently "standalone" in the context of its operation (i.e., it determines ammonia concentration without human-in-the-loop interpretation influencing the measurement result itself). The performance studies mentioned (sensitivity, imprecision, method comparison) would be a direct assessment of its standalone capability.
7. The type of ground truth used
For an in-vitro diagnostic device measuring a specific analyte like ammonia, the "ground truth" for performance evaluations would generally be:
- Known concentrations: For sensitivity and imprecision, this would involve using commercially available or custom-prepared control samples with a precisely known concentration of ammonia.
- Reference method comparison: For method comparison, it would involve testing patient samples using both the Sentinel Ammonia Ultra Diagnostic Assay and a legally marketed, well-established reference method (predicate device in this case) or a recognized gold standard method to assess concordance.
The document states that "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." This implies using a calibrated standard for accurate quantification, which serves as a form of ground truth for instrument calibration.
8. The sample size for the training set
The concept of a "training set" in the context of machine learning is not directly applicable to this enzymatic in-vitro diagnostic assay. These assays are based on established biochemical reactions, and their performance is optimized through reagent formulation, calibration, and validation, not typically through machine learning model training on large datasets in the conventional sense. Therefore, no "training set sample size" is reported.
9. How the ground truth for the training set was established
As explained above, there isn't a "training set" in the machine learning sense for this type of device. The accuracy of the assay is based on the chemical principle (enzymatic reaction converting NADH) and the use of a calibrated standard (500 µg/dL ammonia standard) to establish the relationship between absorbance change and ammonia concentration.
{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 LucaManaging DirectorSentinel CH SrlVia Principe Eugenio20155 Milan, ItalyTel.: +39 02 345514 1Fax: +39 02 345514 64e-mail: sentinel@sentinel.it |
|---|---|
| 2. Contact person: | Mr. Davide SpadaApplication SpecialistSentinel CH SrlVia Principe Eugenio20155 Milan, ItalyTel.: +39 02 345514 1Fax: +39 02 345514 64e-mail: spada@sentinel.it |
| 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 | Classificationpanel | Regulatoryclass | ProductCode |
|---|---|---|---|---|
| ------------------- | ----------------- | ------------------------- | --------------------- | ----------------- |
| Trade/Device Name | Regulation name | Classification panel | Regulatory class | Product Code |
|---|---|---|---|---|
| Ammonia Ultra | Enzymatic Method,Ammonia | ClinicalChemistry | I | JIF |
| Ammonia Control | Single (Specified)Analyte Controls(Assayed andUnassayed) | ClinicalChemistry | 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-IncorporatingDynamicStabilizationTechnology | Trace America, Inc | K974620 | 02 Jan. 1998 |
| 2 | Ammonia Controls | QuantimetrixAmmonia 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 (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 I ou may of and 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
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
§ 862.1065 Ammonia test system.
(a)
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.(b)
Classification. Class I.