(52 days)
The Ammonia II assay is an enzymatic in vitro test for the quantitative determination of ammonia in human plasma on Roche/Hitachi cobas c systems.
Ammonia measurements are used in the diagnosis and treatment of severe liver disorders, such as cirrhosis, hepatitis, and Reye's syndrome.
The Ammonia II (NH3L2) assay is an enzymatic in vitro test for the quantitative determination of ammonia in human plasma on Roche/Hitachi cobas c systems. The Ammonia II assay is an enzymatic method, with glutamate dehydrogenase.
This document describes the Ammonia II assay for the quantitative determination of ammonia in human plasma. Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally qualitative ("All data passed the predetermined acceptance criteria") rather than specific numerical thresholds presented in a consolidated table. However, the reported performance data for each test indicates the values achieved. Based on the provided text, a summary of performance can be extracted:
Ammonia II Assay Performance Summary
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (Intermediate) | All data passed predetermined acceptance criteria. | AMM-N (67.9 µmol/L): SD 1.61 µmol/L, CV 2.4%AMM-P (243 µmol/L): SD 4.26 µmol/L, CV 1.8%Plasma 1 (26.0 µmol/L): SD 1.29 µmol/L, CV 4.9%Plasma 2 (57.7 µmol/L): SD 1.72 µmol/L, CV 3.0%Plasma 3 (110 µmol/L): SD 1.92 µmol/L, CV 1.7%Plasma 4 (480 µmol/L): SD 6.30 µmol/L, CV 1.3%Plasma 5 (853 µmol/L): SD 12.4 µmol/L, CV 1.5% |
| Limit of Blank (LoB) | ≤ 10 µmol/L | 1.80 µmol/L |
| Limit of Detection (LoD) | ≤ 10 µmol/L | 3.46 µmol/L |
| Limit of Quantitation (LoQ) | ≤ 10 µmol/L | 9.36 µmol/L |
| Linearity | Correlation coefficient (r²) approaching 1.000 for linear fit. | Lot 1: y = 1.003x - 2.19, r² = 0.9999Lot 2: y = 1.002x - 1.30, r² = 1Lot 3: y = 1.002x - 1.56, r² = 0.9999 |
| Endogenous Interference | No significant interference (implicitly, within specified levels). | Hemolysis (114-146 mg/dL): Passed at 36.1-91.8 µmol/L AmmoniaUnconjugated Bilirubin (68-69 mg/dL): Passed at 46.4-113 µmol/L AmmoniaConjugated Bilirubin (64 mg/dL): Passed at 40.2-89.1 µmol/L AmmoniaLipemia (764-771 mg/dL): Passed at 51.5-92.7 µmol/L AmmoniaAlbumin (77.2-77.5 g/L): Passed at 47.2-108 µmol/L AmmoniaImmunoglobulin (IgG) (71.4-71.7 g/L): Passed at 41.5-83.9 µmol/L Ammonia |
| Exogenous Interference (Drugs) | No interference at therapeutic concentrations (except noted). | No interference found for common drug panels with the exceptions of Cefoxitin, Sulfasalazin, and Temozolomid. |
| Matrix Comparison | Correlation (Pearson (r)) approaching 1.000, slope near 1.0, intercept near 0.0. | Lot 1: y = 1.002x – 1.18, r = 1.000Lot 2: y = 0.987x – 0.77, r = 1.000Lot 3: y = 1.005x – 1.39, r = 1.000 |
| Method Comparison (Predicate) | Correlation (r) approaching 1.000, slope near 1.0, intercept near 0.0. | y = 1.001x – 1.90 µmol/L, r = 1.000 |
2. Sample sizes used for the test set and the data provenance
- Precision: Not explicitly stated as a "test set" in the context of diagnostic accuracy but involves replicate measurements of various controls and human plasma samples over 21 days.
- LoB, LoD, LoQ:
- LoB: One analyte-free sample measured with three lots in 10-fold determination in 6 runs (60 measurements per lot).
- LoD: Five samples with low-analyte concentration measured with three lots in two-fold determination in 6 runs (60 measurements per lot).
- LoQ: A low-level sample set (7 human plasma samples) tested in 5 replicates per sample on 5 days.
- Linearity: Not explicitly stated, typically involves a range of spiked samples.
- Endogenous Interferences: Pooled human plasma samples spiked with varying levels of interferent (10 dilution steps per sample), tested in triplicate.
- Exogenous Interferences (Drugs): Two sample pools (low and high NH3L2), each divided into aliquots. Reference aliquot (not spiked) tested n=3. Spiked aliquots tested in triplicate.
- Matrix Comparison: 52-53 tubes of K2 EDTA plasma and 52-53 tubes of K3 EDTA plasma for each of 3 reagent lots (total of ~156-159 tubes per anticoagulant type).
- Method Comparison to Predicate: 112 human plasma samples.
Data Provenance: The document generally refers to "human plasma" samples, suggesting human subjects. The country of origin is not specified but given the submitter is Roche Diagnostics (with registration numbers for Mannheim, Germany, Penzberg, Germany, and the United States), the data could be from multiple regions. The studies are prospective performance evaluations of the device conducted according to CLSI guidelines.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This device is an in vitro diagnostic (IVD) assay for quantitative measurement. The "ground truth" for the performance characteristics (precision, limits, linearity, interference) is established by analytical methods and reference materials, not by expert interpretation of images or clinical cases.
4. Adjudication method for the test set
Not applicable. This is an IVD assay, and the studies are analytical performance evaluations, not clinical studies involving expert adjudication of diagnostics results or images.
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 an IVD assay for quantitative ammonia measurement, not an AI-powered diagnostic imaging device or a decision support system for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, directly. The studies described (Precision, LoB/LoD/LoQ, Linearity, Interference, Matrix Comparison, Method Comparison) evaluate the analytical performance of the Ammonia II assay itself, without a human-in-the-loop component for result generation. The device (Ammonia II assay on Roche/Hitachi cobas c systems) performs the quantitative determination of ammonia.
7. The type of ground truth used
The ground truth used for these analytical studies is based on:
- Reference materials and spiked samples: For linearity, LoB/LoD/LoQ, and interference studies, known concentrations of analyte or interferents are used to challenge the assay.
- Statistical methods: For precision, calculations of SD and CV reflect the inherent variability.
- Comparative methods: For method comparison, the results are compared against a legally marketed predicate device (Beckman Coulter Ammonia assay) using statistical regression.
- Clinical Laboratory Standards Institute (CLSI) guidelines: These guidelines (EP05-A3, EP17-A2, EP06-A) provide standardized methodologies for establishing analytical performance, which inherently define how "ground truth" is approached for these types of assays.
8. The sample size for the training set
Not applicable. This is not a machine learning or AI device that requires a distinct "training set." The performance studies are analytical evaluations of a chemical assay.
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the context of this device.
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February 8, 2019
Roche Diagnostics Operations (RDO) Noel Mencias Principal, Regulatory Affairs 9115 Hague Road Indianapolis, IN 46250
Re: K183517
Trade/Device Name: Ammonia II Regulation Number: 21 CFR 862.1065 Regulation Name: Ammonia test system Regulatory Class: Class I, reserved Product Code: JIF Dated: December 17, 2018 Received: December 18, 2018
Dear Noel Mencias:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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
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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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). 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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K183517
Device Name Ammonia II
Indications for Use (Describe)
The Ammonia II assay is an enzymatic in vitro test for the quantitative determination of ammonia in human plasma on Roche/Hitachi cobas c systems.
Ammonia measurements are used in the diagnosis and treatment of severe liver disorders, such as cirrhosis, hepatitis, and Reye's syndrome.
Type of Use (Select one or both, as applicable)
| ☒ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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Ammonia II
510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Ammonia II assay
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague RoadIndianapolis, IN 46250-0457 |
| Contact | Noel B. MenciasPhone: (317) 521-3172FAX: (317) 521-2324Email: noel.mencias@roche.com |
| Date Prepared | December 17, 2018 |
| Proprietary Name | Ammonia II |
| Common Name | Ammonia |
| Classification Name | Ammonia test system |
| Product Codes,Regulation Numbers | JIF, 21 CFR 862.1065 |
| Predicate Devices | Beckman Coulter Ammonia |
| EstablishmentRegistration | For the Ammonia II assay, the establishment registration numberfor Roche Diagnostics GmbH in Mannheim, Germany is 9610126,and for Penzberg, Germany, 9610529. The establishmentregistration number for Roche Diagnostics in the United States is1823260. |
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DEVICE DESCRIPTION 1.
The Ammonia II (NH3L2) assay is an enzymatic in vitro test for the quantitative determination of ammonia in human plasma on Roche/Hitachi cobas c systems. The Ammonia II assay is an enzymatic method, with glutamate dehydrogenase.
2. INDICATIONS FOR USE
The Ammonia II assay is an enzymatic in vitro test for the quantitative determination of ammonia in human plasma on Roche/Hitachi cobas c systems.
Ammonia measurements are used in the diagnosis and treatment of severe liver disorders, such as cirrhosis, hepatitis, and Reye's syndrome.
TECHNOLOGICAL CHARACTERISTICS 3.
The Ammonia II assay is an enzymatic method, with glutamate dehydrogenase. Glutamate dehydrogenase (GLDH) catalyzes the reductive amination of 2-oxoglutarate with NH4+ and NADPH to form glutamate and NADP+. The concentration of the NADP+ formed is directly proportional to the ammonia concentration. It is determined by measuring the decrease in absorbance.
The following tables compare the Ammonia II (NH3L2) assay with its predicate device, SYNCHRON Systems Ammonia Reagent (K003196).
| Feature | SYNCHRON SystemsAmmonia Reagent (K003196) | Ammonia II |
|---|---|---|
| Intended Use | AMM reagent, when used inconjunction with UniCel®DxC 600/800 System(s) andSYNCHRON® SystemsAmmoniaCalibrators, is intended for thequantitative determination ofammonia concentration inhuman plasma. | The Ammonia II assay is anenzymatic in vitro test for thequantitative determination ofammonia in human plasma onRoche/Hitachi cobas c systems. |
| Feature | SYNCHRON SystemsAmmonia Reagent (K003196) | Ammonia II |
| Test Principle | The SYNCHRON® System(s)automatically proportions theappropriate sample and reagentvolumes into a cuvette. Theratio used is one part sample to6 parts reagents. The systemmonitors the change inabsorbance at 340 nanometers.This change in absorbance isdirectly proportional to theconcentration of ammonia inthe sample and is used by theSYNCHRON® System(s) tocalculate and express theammonia concentration. | Enzymatic method, withglutamate dehydrogenase.Glutamate dehydrogenase(GLDH) catalyzes the reductiveamination of2-oxoglutarate with NH4+ andNADPH to form glutamate andNADP+.The concentration of the NADP+formed is directly proportional tothe ammonia concentration. It isdetermined by measuring thedecrease in absorbance. |
| Instrument | UniCel DxC 600/800System(s) and SYNCHRONSystems | cobas c 501 |
| Reagent Composition | REAGENT CONSTITUENTSα-Ketoglutarate 3.23 mmol/LADP 1.9 mmol/LNADPH 0.22 mmol/LGLDH (Beef liver) >10 U/L | R1 BICINEa) buffer: 300mmol/L, pH 8.3; GLDH(microbial): ≥ 16.7 µkat/L;detergents; preservativeR3 GLDH (microbial): ≥ 5.0µkat/L; 2-oxoglutarate: 78mmol/L;NADPH: ≥ 1.3 mmol/L;nonreactive buffera) BICINE = N,N-bis(2-hydroxyethyl)-glycine |
| Sample Type/Matrix | Sodium HeparinEDTA | K2- and K3-EDTA plasma |
| Calibrator | SYNCHRON SystemsAmmonia Calibrators | Ammonia/Ethanol/CO2Calibrator |
| Calibration Interval | Under typical operatingconditions the AMM reagentcartridge must be calibratedevery 5 days and also withcertain parts replacement ormaintenance procedures, asdefined in the UniCel DxC600/800 System InstructionsFor Use (IFU) manual. | Calibration frequency 2-pointcalibration- after lot change- automatically every 14 days- as required following qualitycontrolprocedures |
| Feature | SYNCHRON SystemsAmmonia Reagent (K003196) | Ammonia II |
| Controls | At least two levels of controlmaterial | Ammonia/Ethanol/CO2 ControlNormalAmmonia/Ethanol/CO2 ControlAbnormal |
| Traceability/Standardization | Ammonia measurand (analyte)in this calibrator is traceable tothe manufacturer's selectedmeasuring method. Thetraceability process is based onprEN ISO 17511. | This method has beenstandardized against a primarystandard. |
| Reagent Stability | AMM reagent, when storedunopened at +2°C to +8°C,will remain stable until theexpiration date printed on thelabel. | Shelf life at 2-8 °C: Seeexpiration date on cobas c packlabel. |
| Reagent On-Board Stability | Once opened, the reagent isstable for 30 days at +2°C to+8°C unless the expiration dateis exceeded. | On-board in use and refrigeratedon the analyzer: 16 weeks |
| Measuring Range | 16 - 1700 µg/dL (9 – 1000µmol/L) | 10-1000 µmol/L (17-1703µg/dL) |
| Lower Limits ofMeasurement | lower limit of 9 µmol/L (16µg/dL) | Limit of Blank = 10 µmol/L (17µg/dL)Limit of Detection = 10 µmol/L(17 µg/dL)Limit of Quantitation = 10µmol/L (17 µg/dL) |
| Sample Stability | Tubes should be filledcompletely, mixed gently byinversion, placed on ice,centrifuged immediately for 10minutes at an RCF of 1500Gand analyzed within 30minutes. Samples should not befrozen. The tubes should betightly stoppered at all times. | Stability in plasma:30 min at 15-25 °C2 hours at 2-8 °C3 days at -20 ± 5 °C4 weeks at (-60)-(-90) °C (atleast) |
Table 1: Assay Comparison
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NON-CLINICAL PERFORMANCE EVALUATION 4.
The following performance data were provided in support of the substantial equivalence determination:
Precision according to CLSI EP05-A3
Detection Limit: LoB, LoD, LoQ according to CLSI EP17-A2
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Linearity according to CLSI EP06-A
Endogenous Interferences
Exogenous Interferences – Drugs
Method Comparison to Predicate
Matrix Comparison - Anticoagulants.
Precision 4.1.
- Repeatability and Intermediate Precision 4.1.1.
Precision experiments were performed in accordance with CLSI Guideline EP5-A3. Two aliquots per run, two runs per day for ≥ 21 days were performed on the same analyzer using 3 lots of reagent. Repeatability (within run precision) and intermediate precision (within lab precision) were calculated. The samples were randomized in each run separately. For each sample, the following were calculated: Mean, Repeatability and intermediate precision as CV and SD values, and the upper 95% confidence interval for SD and CV values.
| Specimen | Mean (µmol/L) | SD (µmol/L) | CV (%) |
|---|---|---|---|
| AMM-N | 66.6 | 1.40 | 2.1 |
| AMM-P | 243 | 3.45 | 1.4 |
| Human Plasma 1 | 26.0 | 1.26 | 4.8 |
| Human Plasma 2 | 57.7 | 1.63 | 2.8 |
| Human Plasma 3 | 110 | 1.62 | 1.5 |
| Human Plasma 4 | 492 | 4.12 | 0.8 |
| Human Plasma 5 | 863 | 9.54 | 1.1 |
Table 3: Intermediate Precision Summary
| Specimen | Mean (umol/L) | SD (umol/L) | CV (%) |
|---|---|---|---|
| AMM-N | 67.9 | 1.61 | 2.4 |
| AMM-P | 243 | 4.26 | 1.8 |
| Human Plasma 1 | 26.0 | 1.29 | 4.9 |
| Human Plasma 2 | 57.7 | 1.72 | 3.0 |
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| Specimen | Mean ( $\u03bcmol$ /L) | SD ( $\u03bcmol$ /L) | CV (%) |
|---|---|---|---|
| Human Plasma 3 | 110 | 1.92 | 1.7 |
| Human Plasma 4 | 480 | 6.30 | 1.3 |
| Human Plasma 5 | 853 | 12.4 | 1.5 |
All data passed the predetermined acceptance criteria.
Analytical Sensitivity 4.2.
LoB, LoD, and LoQ were determined according to CLSI EP17-A2.
- Limit of Blank (LoB) 4.2.1.
Limit of Blank determines the highest observed measurement values for samples free of analyte.
For determination of LoB one analyte free sample was measured with three lots in 10-fold determination in 6 runs, distributed over 3 days, on one cobas c 501 analyzer. In total, 60 measurements were obtained per lot. Data analysis is based on determination of the 95th percentile of the 60 measured values
Limit of Detection (LoD) 4.2.2.
The LoD determines the lower limit for samples with analyte. The LoD was determined as the lowest amount of analyte in a sample that can be detected with a 95% probability.
For determination of LoD five samples with low-analyte concentration (approximately up to 4 times the LoB) were measured with three lots in two-fold determination in 6 runs, distributed over 3 days, on one cobas c 501 analyzer. In total 60 measurements were obtained per lot.
Limit of Quantitation (LoQ) 4.2.3.
The limit of quantitation (LoQ), according to EP17-A2 is the lowest analyte concentration that can be quantitatively determined with a stated acceptable precision and trueness under stated experimental conditions.
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A low level sample Set was prepared by diluting 7 human plasma samples with water. The low level sample set was tested in 5 replicates per sample on 5 days, one run per day on one cobas c 501 analyzer.
| Result (µmol/L) | Claim (µmol/L) | |
|---|---|---|
| Limit of Blank (LoB) | 1.80 | ≤ 10 µmol/L |
| Limit of Detection (LoD) | 3.46 | ≤ 10 µmol/L |
| Limit of Quantitation (LoQ) | 9.36 | ≤ 10 µmol/L |
Table 4: LoB, LoD, and LoQ Experimental Determination
All data passed the predetermined acceptance criteria.
Linearity/Assay Reportable Range 4.3.
Regression Analysis 4.3.1.
The linearity study was conducted to demonstrate that measurements across the claimed measuring range for each parameter are linear. The study was performed according to CLSI guideline EP06-A.
A linearity check was performed with first order (linear) regression and then with higher order models (quadratic and cubic).
Table 5: Linearity Results
| Reagent Lot | Linear Regression |
|---|---|
| 1 | $y = 1.003x - 2.19$correlation coefficient (r²) = 0.9999 |
| 2 | $y = 1.002x - 1.30$correlation coefficient (r²) = 1 |
| 3 | $y = 1.002x -1.56$correlation coefficient (r²) = 0.9999 |
All data passed the predetermined acceptance criteria.
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Endogenous Interferences 4.4.
Hemolysis/Bilirubin/Lipemia/Albumin/IgG 4.4.1.
The effects of interference by hemoglobin, lipemia (Intralipid), Albumin, Immunoglobulin (IgG) and Bilirubin on the NH3L2 test system were determined on the cobas c 501 analyzer using pooled human plasma samples spiked with varying levels of interferent. The resulting sample series (10 dilution steps per sample) were tested in triplicate and the median values used to calculate % recovery, by comparing the measured concentration to the expected concentration (which is the NH3L2 concentration when no interferent was added).
| Substance tested | Tested SubstanceApproximate Concentration | Ammonia concentrations inumol/L |
|---|---|---|
| Hemolysis | Level 1: 114 mg/dLLevel 2: 146 mg/dL | Level 1: 36.1Level 2: 91.8 |
| Unconjugated Bilirubin | Level 1: 69 mg/dLLevel 2: 68 mg/dL | Level 1: 46.4Level 2: 113 |
| Conjugated Bilirubin | Level 1: 64 mg/dLLevel 2: 64 mg/dL | Level 1: 40.2Level 2: 89.1 |
| Lipemia (Intralipid) | Level 1: 764 mg/dLLevel 2: 771 mg/dL | Level 1: 51.5Level 2: 92.7 |
| Albumin | Level 1: 77.5 g/LLevel 2: 77.2 g/L | Level 1: 47.2Level 2: 108 |
| Immunoglobulin (IgG) | Level 1: 71.7 g/LLevel 2: 71.4 g/L | Level 1: 41.5Level 2: 83.9 |
Table 6: Endogenous Interference Results
Listed are the highest levels of interferent which passed specification at the analyte concentration levels. All data passed the predetermined acceptance criteria.
Exogenous Interferences – Drugs 4.5.
The purpose of this study was to evaluate drugs for potential interference with NH3L2 assay measured on the cobas c 501 analyzer. Two sample pools, containing a low and high concentration of NH3L2 were used. These sample pools were divided into an appropriate number of aliquots. One aliquot was not spiked with the drugs and it was used as the reference
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sample for NH3L2 concentration. The NH3L2 concentration in the sample was determined with n = 3 measurements on a cobas c 501 analyzer.
The other sample aliquots, with either the high or low NH3L2 concentrations, are spiked with the respective amount of drug. The NH3L2 concentration of the spiked aliquots are determined in triplicate and the mean of the triplicate determinations is compared to the NH3L2 concentration determined for the reference aliquot (mean of n=3).
No interference was found at therapeutic concentrations using common drug panels with the exceptions of Cefoxitin, Sulfasalazin, and Temozolomid which were found to interfere.
4.6. Sample Matrix Comparison
The effect of the presence of anticoagulants on analyte recovery was determined by method comparison, obtained from samples drawn into different types of plasma collection tubes (K2 EDTA and K3 EDTA). For K2 EDTA and K3 EDTA 52 tubes for Lot 1 and 53 tubes for Lot 2 and 53 tubes for Lot 3 were collected and filled completely.
Method comparison K2 EDTA versus K3 EDTA were calculated. Slope, Intercept and Correlation were calculated.
| Reagent Lot | Regression | Correlation (Pearson(r)) |
|---|---|---|
| 1 | $y = 1.002x -1.18$ | 1.000 |
| 2 | $y = 0.987x - 0.77$ | 1.000 |
| 3 | $y = 1.005x - 1.39$ | 1.000 |
4.7. Method Comparison to Predicate
A total of 112 human plasma samples were tested in singlicate with the AMM test kit of Beckmann Coulter on Beckmann Synchron DxC 800 and the NH3L2 reagent on cobas c 501. The results were calculated using Passing/Bablok, and Linear regression.
Regression analysis results:
y = 1.001x – 1.90 µmol/L, r = 1.000
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5. CLINICAL PERFORMANCE EVALUATION
Not applicable.
6. ADDITIONAL INFORMATION
6.1. Other Devices Marketed with This Assay
The Ammonia II assay continues to use:
Ammonia/Ethanol/CO2 Calibrator (K031880)
Ammonia/Ethanol/CO2 Control Normal (K031880)
Ammonia/Ethanol/CO2 Control Abnormal (K031880)
7. CONCLUSIONS
The submitted information in this premarket notification supports a substantial equivalence decision.
§ 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.