(161 days)
The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance. For in vitro diagnostic use only.
RX imola is an automated clinical chemistry analyzer complete with dedicated analyzer software. Software functions of the analyzer include the facility to interact with a host computer for direct download of test method selection details for individual samples. A barcode system is used for the rapid identification of patient samples, reagents and QC samples, In addition, the RX imola is fitted with an Ion Selective Electrode (ISE) module that operates in conjunction with specific electrodes for the quantitative in vitro diagnostic determination of Sodium, Potassium and Chloride in serum and urine.
The provided document is a 510(k) summary for a medical device (ISE Electrodes) and outlines the performance characteristics to demonstrate substantial equivalence to a predicate device. It focuses on the analytical performance of the device rather than a clinical study involving human patients or complex AI algorithms. Therefore, many of the requested points related to multi-reader multi-case studies, expert ground truth establishment for AI, and training/test set sample sizes for AI are not applicable to this type of submission.
The document details the acceptance criteria and the study that proves the device meets those criteria for analytical performance.
1. Table of Acceptance Criteria and Reported Device Performance
For this type of device (Ion Selective Electrodes for measuring common electrolytes), the "acceptance criteria" are typically defined by demonstrating that the new modified device performs equivalently to the existing cleared predicate device and meets established analytical performance guidelines (e.g., CLSI standards for precision, linearity, and interference). The document implicitly defines acceptance by stating "The acceptance criteria ... was met" or "The results... support the claimed measuring ranges."
Here's a summary of the performance demonstrated based on the provided text:
| Performance Metric | Analyte & Specimen Type | Acceptance Criteria (Implicit - based on meeting CLSI/predicate equivalence) | Reported Device Performance |
|---|---|---|---|
| Precision/Reproducibility | Sodium, Potassium, Chloride (Serum & Urine) | Met CLSI EP05-A3 guidelines for 'Evaluation of Precision of Quantitative Measurement Procedures'; demonstrated acceptable CVs/SDs comparable to predicate. | Sodium (Serum): CV% (Total Precision) ranged from 1.1% to 2.2% |
| Potassium (Serum): CV% (Total Precision) ranged from 0.9% to 4.1% | |||
| Chloride (Serum): CV% (Total Precision) ranged from 0.9% to 2.2% | |||
| Sodium (Urine): CV% (Total Precision) ranged from 2.4% to 5.9% | |||
| Potassium (Urine): CV% (Total Precision) ranged from 2.2% to 4.0% | |||
| Chloride (Urine): CV% (Total Precision) ranged from 2.3% to 3.6% | |||
| Linearity/Reportable Range | Sodium (Serum): 90-200 mmol/L | Met CLSI EP6-A guidelines for 'Evaluation of the Linearity of Quantitative Measurement Procedures'; deviation from linearity less than 5%. | Sodium (Serum): 90 to 200 mmol/L supported. |
| Sodium (Urine): 45-318 mmol/L | Sodium (Urine): 45 to 318 mmol/L supported. | ||
| Potassium (Serum): 0.5-11 mmol/L | Potassium (Serum): 0.5 to 11 mmol/L supported. | ||
| Potassium (Urine): 7-168 mmol/L | Potassium (Urine): 7 to 168 mmol/L supported. | ||
| Chloride (Serum): 72-210 mmol/L | Chloride (Serum): 72 to 210 mmol/L supported. | ||
| Chloride (Urine): 61-319 mmol/L | Chloride (Urine): 61 to 319 mmol/L supported. | ||
| Specificity/Interference | Sodium, Potassium, Chloride (Serum & Urine) | Met EP07 3rd Edition 'Interference Testing in Clinical Chemistry'; demonstrated no significant interference up to specified levels for various substances (e.g., Hemoglobin, Bilirubin, Triglycerides). | No significant interference observed for detailed endogenous and exogenous substances at specified levels in serum and urine. |
| Method Comparison (Correlation with Predicate) | Sodium (Serum) | Linear regression equation and correlation coefficient (R) demonstrating strong correlation to predicate device. | Y = 1.06x - 8.4 kg/mol, R = 0.973 |
| Potassium (Serum) | Y = 1.02x - 0.09, R = 0.998 | ||
| Chloride (Serum) | Y = 1.03x - 6.59, R = 0.987 | ||
| Sodium (Urine) | Y = 0.92x + 6.43, R = 0.997 | ||
| Potassium (Urine) | Y = 1.03x = 1.02, R = 0.999 | ||
| Chloride (Urine) | Y = 0.89x + 18.49, R = 0.986 |
2. Sample Size Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples used for analytical validation studies.
- Precision Studies:
- Serum: Two levels of control material and at least five human serum samples for each analyte (Sodium, Potassium, Chloride). Tested twice per day for 20 non-consecutive days, two replicates per run. This totals
80data points per measured sample/control (20 days * 2 runs/day * 2 replicates/run). - Urine: Two levels of urine controls and at least five urine patient pools for each analyte. Tested twice per day for 20 non-consecutive days, two replicates per run. This totals
80data points per measured sample/control.
- Serum: Two levels of control material and at least five human serum samples for each analyte (Sodium, Potassium, Chloride). Tested twice per day for 20 non-consecutive days, two replicates per run. This totals
- Linearity Studies: 9 levels of samples used for each analyte and specimen type.
- Method Comparison (Correlation):
- Serum: 105 patient serum samples for Sodium, 109 for Potassium, 104 for Chloride.
- Urine: 72 patient urine samples for Sodium, 84 for Potassium, 90 for Chloride.
- Data Provenance: The document does not explicitly state the country of origin for the patient samples. The studies were conducted in-house by Randox Laboratories Limited, which is based in the United Kingdom. The studies were retrospective in the sense that they used collected samples to validate the device's performance, not in the sense of analyzing pre-existing patient data outside a controlled study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- N/A. This is an in vitro diagnostic (IVD) device for measuring electrolyte concentrations using Ion Selective Electrodes. The "ground truth" for analytical performance studies is established by quantitative measurements using reference methods or by the known concentrations of controls/calibrators, not by human expert interpretation like radiologists.
4. Adjudication Method for the Test Set
- N/A. As this is an analytical performance study for an IVD device, there is no human adjudication method required. Performance is based on quantitative measurements.
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
- N/A. This is not an AI-based device, nor is it a device that involves human "readers" interpreting images or clinical data. Therefore, an MRMC study is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Partially Applicable / Context Dependent. The device (ISE Electrodes on the RX Imola) performs measurements automatically. The performance data presented (precision, linearity, interference, method comparison) is the "standalone" performance of the device as it directly measures the analytes, without requiring human "interpretation" of the analytical result itself beyond standard lab procedures. There is no separate algorithm being tested in the AI sense.
7. The Type of Ground Truth Used
- Reference Method / Known Concentration:
- For precision and linearity studies, ground truth is established by using control materials and prepared linearity samples with known, validated concentrations or statistically derived consensus values from repeated measurements.
- For method comparison, the "ground truth" is effectively the measurements obtained from the predicate device (the RX imola with the previous ISE unit, K052914), against which the new device (RX imola with new ISE electrodes, K230890) is correlated to demonstrate equivalence.
- For interference studies, known interfering substances are added at specific concentrations to samples to evaluate their effect on the measurement.
8. The Sample Size for the Training Set
- N/A (in the AI/machine learning sense). This device does not involve a "training set" in the context of machine learning. It's a chemical measurement system with established electrochemical principles. Standard calibration and quality control procedures are part of its normal operation, but these are not "training sets" in the AI development sense.
9. How the Ground Truth for the Training Set Was Established
- N/A (in the AI/machine learning sense). As there is no AI training set, this question is not applicable. The device's operational "knowledge" comes from its manufacturing specifications, calibration protocols using reference materials, and the underlying physical and chemical principles of ion-selective electrodes.
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September 8, 2023
Randox Laboratories Limited Karena Shaw Regulatory Affairs Manager 55 Diamond Road County Antrim, BT29 40Y United Kingdom
Re: K230890
Trade/Device Name: ISE Electrodes Regulation Number: 21 CFR 862.1600 Regulation Name: Potassium Test System Regulatory Class: Class II Product Code: CEM, CGZ, JGS Dated: August 11, 2023 Received: August 11, 2023
Dear Karena Shaw:
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 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
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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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K230890
Device Name ISE Electrodes
Indications for Use (Describe)
The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance.
For in vitro diagnostic use only.
| 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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SPECIAL 510(k) SUMMARY K230890
General Information
Name: Randox Laboratories Limited
55 Diamond Road, Crumlin, Address: County Antrim, BT29 4QY, United Kingdom.
Telephone: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912
Contact: Karena Shaw E-mail: karena.shaw@randox.com
Device Identification
Proprietary Names: ISE Electrodes
Table 1: Candidate Device Regulatory Summary
| ProductCode | Regulation Name | Classification | Regulation Section | Panel |
|---|---|---|---|---|
| CEM | Electrode, Ion-Specific,Potassium | II | 21 CFR 862.1600 | Clinical Chemistry(75) |
| CGZ | Electrode, Ion-Specific,Chloride | II | 21 CFR 862.1170 | Clinical Chemistry(75) |
| JGS | Electrode, Ion-Specific,Sodium | II | 21 CFR 862.1665 | Clinical Chemistry(75) |
Predicate Device:
Previously cleared unmodified device: RX imola (K052914)
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DEVICE DESCRIPTION
RX imola is an automated clinical chemistry analyzer complete with dedicated analyzer software. Software functions of the analyzer include the facility to interact with a host computer for direct download of test method selection details for individual samples. A barcode system is used for the rapid identification of patient samples, reagents and QC samples,
In addition, the RX imola is fitted with an Ion Selective Electrode (ISE) module that operates in conjunction with specific electrodes for the quantitative in vitro diagnostic determination of Sodium, Potassium and Chloride in serum and urine.
INTENDED USE
The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance.
For in vitro diagnostic use only.
DESCRIPTION OF MODIFICATION TO EXISTING DEVICE
Following discontinuation of the original ISE unit, the RX imola instruments purchased will now be fitted with a new ISE electrodes for Sodium, Potassium & Chlorides. RX imola instruments fitted with the new ISE electrodes will be identified by an alternate serial number prefix (7255).
The new ISE unit being implemented through this Special 510(k) was previously cleared under K131554 for our RX DAYTONA PLUS CHEMISTRY ANALYZER. The data included in this Special 510(k) summary is based on a comparison of the original ISE electrodes used in conjunction with RX imola (K052914) and the new ISE electrodes that will now be used with the RX imola.
COMPARISON WITH PREDICATE DEVICE
The following table describes the similarities and differences between
- ISE device originally cleared with the RX imola through K052914 .
- Candidate ISE device with the RX imola analyser ●
Table 2: Comparison with predicate device
Similarities
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| Parameter | RX imolaAutomated AnalyzerWith previous ISE unit(ORIGINALLY CLEARED DEVICEK052914) | RX imolaAutomated AnalyzerWith New ISE Unit(CANDIDATE DEVICEK230890) |
|---|---|---|
| Intended Use | Used for measurement of the electrolytessodium, potassium and chloride in serumand urine for diagnosis and treatment ofelectrolyte imbalance | Used for measurement of the electrolytessodium, potassium and chloride in serum andurine for diagnosis and treatment ofelectrolyte imbalance |
| Method | Direct | Direct |
| CalibrationFrequency | 8 Hours | 8 Hours |
| ISEElectrodesUsage[10 000Samples] | REF: 360 DaysNa+: 360 DaysK+: 180 DaysCl-: 90 Days | REF: 360 DaysNa+: 360 DaysK+: 180 DaysCl-: 90 Days |
| ISE SampleTypes | SerumUrine | SerumUrine |
| EnvironmentalOperatingTemperature | 15°C to 30°C | 15°C to 30°C |
| Parameter | RX imolaAutomated AnalyzerWith previous ISE unit(ORIGINALLY CLEARED DEVICEK052914) | RX imolaAutomated AnalyzerWith New ISE Unit(CANDIDATE DEVICEK230890) |
| ISEThroughput | 240 tests per hour | 180 tests per hour |
| Consumables | Medica: Reference Electrode | Horiba: Reference Electrode |
| Medica: Sodium Electrode (Na+) | Horiba: Sodium Electrode (Na+) | |
| Medica: Potassium (K+) | Horiba: Potassium (K+) | |
| Medica: Chloride (Cl-) | Horiba: Chloride (Cl-) | |
| Medica: CAL A | Horiba: L-Solution | |
| Medica: CAL B (Calibrator) | Horiba: H-Solution (Calibrator) | |
| Medica: Clean Solution | Horiba: Clean Solution | |
| Medica: Urine Diluent (for urine ISE) | Horiba: Urine Diluent (for urine ISE) | |
| Horiba: Etching Solution | ||
| Horiba: Ref-Solution | ||
| SampleVolume | 70ul | 53ul |
| CalibrationType | 2-Point(CAL A + CAL B) | 2-Point(L-solution + H-Solution) |
| Analysis Time | Serum - 30s including 1-point calibrationUrine - 60s including 1-point calibration | Serum - 36s including 1 point calibrationUrine - 54s including 1 point calibration |
| ISE ModuleSize | 100mm (H) x 102mm (W) x 91 mm (D) | 175mm (H) x 205mm (W) x 95 mm (D) |
| MaximumEnvironmentalTemperature(UnopenedStorage) | 38°C | 45°C |
| CalibrationPass Range | Na+ pass range (50 mV - 66 mV) | Na+ pass range (38 mV - 65 mV) |
| K+ pass range (50 mV - 63 mV) | K+ pass range (37 mV - 67mV) | |
| Cl- pass range (40 mV - 59 mV) | Cl- pass range (28 mV - 53 mV) |
Differences
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ANALYTICAL PERFORMANCE:
Precision/Reproducibility:
Precision was evaluated consistent with C.L.S.I document EP05-A3 'Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline- Third Edition.' Serum precision studies were performed on two RX imola systems using two levels of control material and at least five human serum samples for Sodium, Potassium and Chloride. Urine precision studies were performed on the same two RX imola systems for Sodium, Potassium and Chloride using two levels of urine controls and at least five urine patient pools. Testing was conducted twice per day for 20 non-consecutive days. Two replicates per run was performed for each sample.
The results are summarized in the tables below:
Table 3: Sodium Serum Precision Summary
| Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 143.72 | 160.93 | 101.68 | 111.00 | 118.67 | 136.38 | 162.38 | 192.10 |
| SD | 0.88 | 1.01 | 0.69 | 0.59 | 1.88 | 0.47 | 2.69 | 0.37 |
| CV (%) | 0.6 | 0.6 | 0.7 | 0.5 | 1.6 | 0.3 | 1.7 | 0.2 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Within run precision
Total precision
| Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 143.72 | 160.93 | 101.68 | 111.00 | 118.67 | 136.38 | 162.38 | 192.10 |
| SD | 1.57 | 2.17 | 2.11 | 1.39 | 2.37 | 1.63 | 3.61 | 3.71 |
| CV (%) | 1.1 | 1.4 | 2.1 | 1.3 | 2.0 | 1.2 | 2.2 | 1.9 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
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Table 4: Potassium Serum Precision Summary
Within run precision
| Control1 | Control2 | SerumPool 1 | SerumPool 2 | SerumPool 3 | SerumPool 4 | SerumPool 5 | SerumPool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 4.00 | 6.43 | 0.91 | 2.16 | 3.26 | 4.56 | 6.58 | 9.73 |
| SD | 0.02 | 0.04 | 0.02 | 0.01 | 0.01 | 0.03 | 0.04 | 0.05 |
| CV (%) | 0.6 | 0.7 | 1.9 | 0.4 | 0.4 | 0.8 | 0.6 | 0.5 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Total precision
| Control1 | Control2 | SerumPool 1 | SerumPool 2 | SerumPool 3 | SerumPool 4 | SerumPool 5 | SerumPool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 4.00 | 6.43 | 0.91 | 2.16 | 3.26 | 4.56 | 6.58 | 9.73 |
| SD | 0.04 | 0.09 | 0.04 | 0.04 | 0.04 | 0.06 | 0.09 | 0.20 |
| CV (%) | 0.9 | 1.4 | 4.1 | 1.6 | 1.3 | 1.2 | 1.4 | 2.1 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Table 5: Chloride Serum Precision Summary
Within run precision
| Control1 | Control2 | SerumPool 2 | SerumPool 3 | SerumPool 4 | SerumPool 5 | |
|---|---|---|---|---|---|---|
| Mean (mmol/l) | 98.27 | 120.99 | 83.30 | 96.14 | 117.38 | 161.10 |
| SD | 0.68 | 0.95 | 0.79 | 0.94 | 0.50 | 0.74 |
| CV (%) | 0.7 | 0.8 | 1.0 | 1.0 | 0.4 | 0.5 |
| n | 80 | 80 | 80 | 80 | 80 | 80 |
Total precision
| Control1 | Control2 | SerumPool 2 | SerumPool 3 | SerumPool 4 | SerumPool 5 | |
|---|---|---|---|---|---|---|
| Mean (mmol/l) | 98.27 | 120.99 | 83.30 | 96.14 | 117.38 | 161.10 |
| SD | 1.04 | 1.54 | 1.85 | 1.02 | 1.06 | 3.55 |
| CV (%) | 1.1 | 1.3 | 2.2 | 1.1 | 0.9 | 2.2 |
| n | 80 | 80 | 80 | 80 | 80 | 80 |
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Table 6: Sodium Urine Precision Summary
Within run precision
| Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |
|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 65.45 | 215.33 | 84.72 | 118.01 | 179.59 | 257.99 | 285.71 |
| SD | 2.48 | 2.83 | 1.91 | 2.41 | 3.08 | 2.88 | 2.77 |
| CV (%) | 3.8 | 1.3 | 2.3 | 2.0 | 1.7 | 1.1 | 1.0 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Total precision
| Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |
|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 65.45 | 215.33 | 84.72 | 118.01 | 179.59 | 257.99 | 285.71 |
| SD | 3.85 | 8.94 | 3.18 | 3.19 | 4.71 | 6.11 | 7.16 |
| CV (%) | 5.9 | 4.2 | 3.8 | 2.7 | 2.6 | 2.4 | 2.5 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Table 7: Potassium Urine Precision Summary
Within run precision
| Control1 | Control2 | UrinePool 2 | UrinePool 3 | UrinePool 4 | UrinePool 5 | |
|---|---|---|---|---|---|---|
| Mean (mmol/l) | 34.49 | 144.18 | 33.54 | 85.89 | 122.59 | 160.81 |
| SD | 0.32 | 0.93 | 0.21 | 0.82 | 0.77 | 1.73 |
| CV (%) | 0.9 | 0.6 | 0.6 | 1.0 | 0.6 | 1.1 |
| n | 80 | 80 | 80 | 80 | 80 | 80 |
Total precision
| Control1 | Control2 | UrinePool 2 | UrinePool 3 | UrinePool 4 | UrinePool 5 | |
|---|---|---|---|---|---|---|
| Mean (mmol/l) | 34.49 | 144.18 | 33.54 | 85.89 | 122.59 | 160.81 |
| SD | 0.77 | 4.80 | 0.73 | 2.49 | 4.10 | 6.50 |
| CV (%) | 2.2 | 3.3 | 2.2 | 2.9 | 3.3 | 4.0 |
| n | 80 | 80 | 80 | 80 | 80 | 80 |
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Table 8: Chloride Urine Precision Summary
Within run precision
| Control1 | Control2 | UrinePool 1 | UrinePool 2 | UrinePool 3 | UrinePool 4 | UrinePool 5 | UrinePool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 86.04 | 280.01 | 85.63 | 93.06 | 146.38 | 198.19 | 247.72 | 315.40 |
| SD | 2.28 | 2.68 | 1.91 | 2.13 | 2.19 | 2.41 | 2.69 | 4.24 |
| CV (%) | 2.7 | 1.0 | 2.2 | 2.3 | 1.5 | 1.2 | 1.1 | 1.3 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Total precision
| Control1 | Control2 | UrinePool 1 | UrinePool 2 | UrinePool 3 | UrinePool 4 | UrinePool 5 | UrinePool 6 | |
|---|---|---|---|---|---|---|---|---|
| Mean (mmol/l) | 86.04 | 280.01 | 85.63 | 93.06 | 146.38 | 198.19 | 247.72 | 315.40 |
| SD | 2.93 | 7.57 | 2.97 | 3.33 | 3.67 | 4.53 | 7.66 | 8.12 |
| CV (%) | 3.4 | 2.7 | 3.5 | 3.6 | 2.5 | 2.3 | 3.1 | 2.6 |
| n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 |
Precision Conclusion
The acceptance criteria for precision was met for serum and urine for all analytes (Sodium, Potassium and Chloride) on the RX imola with the modified ISE device.
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Linearity/assay reportable range:
Linearity studies have been carried out in serum and urine in accordance with C.L.S.I. standard EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline'. Linearity studies were performed at 9 levels to determine the analytical range of an assay - that is the range where the reported result is a linear function to the analyte concentration (or where deviation from linearity is less than 5%).
The linearity samples were prepared at 9 levels to cover the measuring intervals in the table below.
| Analyte | Specimen Type | Measuring Interval (mmol/L) |
|---|---|---|
| Sodium | Serum | 90 to 200 |
| Urine | 45 to 318 | |
| Potassium | Serum | 0.5 to 11 |
| Urine | 7 to 168 | |
| Chloride | Serum | 72 to 210 |
| Urine | 61 to 319 |
Table 9: Linearity Results Summary
Linearity Conclusion
The results of the linearity studies support the above claimed measuring ranges for serum and urine for all analytes (Sodium, Potassium and Chloride) on the RX imola with the modified ISE device.
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Specificity/Interference
Evaluation of specificity/interference was carried out in serum and urine in accordance with EP07 3rd Edition 'Interference Testing in Clinical Chemistry.' The analytes below were tested in serum up to the following levels and were found not to interfere with Sodium, Potassium and Chloride determination.
ISE Sodium, Potassium and Chloride Interference Summary (in Serum) The analytes below were added to normal serum and found not to interfere up to the following levels.
| Sodium - 130 mmol/l | Potassium - 3 mmol/l | Chloride - 90 mmol/l | |
|---|---|---|---|
| Haemoglobin | 1000 mg/dl | 126 mg/dl | 1000 mg/dl |
| Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl |
| Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 49.5 mg/dl |
| Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| IntralipidⓇ | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
Table 10: Analytes Added to Normal Serum Level 1
Table 11: Analytes Added to Normal Serum Level 2
| Sodium - 150 mmol/l | Potassium - 5 mmol/l | Chloride - 110 mmol/l | |
|---|---|---|---|
| Haemoglobin | 1000 mg/dl | 205 mg/dl | 1000 mg/dl |
| Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl |
| Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl |
| Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| Intralipid® | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
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| InterferingSubstance | Sodium 130 mmol/l | Potassium 3 mmol/l | Chloride 90 mmol/l |
|---|---|---|---|
| Bromide | 37.5 mmol/l | 37.5 mmol/l | 37.5 mmol/l |
| Ascorbic Acid | 341 umol/L | 341 umol/L | 341 umol/L |
| Thiocyanate | 6.88 mmol/l | 0.8 mmol/l | 1.12 mmol/l |
| Lithium | 3.2 mmol/l | 3.2 mmol/l | 3.2 mmol/l |
| Salicylic Acid | 4.3 mmol/l | 4.3 mmol/l | 4.3 mmol/l |
Table 12: Exogenous Interferences in Serum - Level 1
Table 13: Exogenous Interferences in Serum - Level 2
| InterferingSubstance | Sodium 150 mmol/l | Potassium 5 mmol/l | Chloride 110 mmol/l |
|---|---|---|---|
| Bromide | 37.5 mmol/l | 37.5 mmol/l | 37.5 mmol/l |
| Ascorbic Acid | 341 µmol/L | 341 µmol/L | 341 µmol/L |
| Thiocyanate | 6.88 mmol/l | 0.85 mmol/l | 1.25 mmol/l |
| Lithium | 3.2 mmol/l | 3.2 mmol/l | 3.2 mmol/l |
| Salicylic Acid | 4.3 mmol/l | 4.3 mmol/l | 4.3 mmol/l |
ISE Sodium, Potassium and Chloride Urine Interference (in urine) summary
The analytes below were added to normal urine and found not to interfere up to the following levels.
Table 14: Analytes Added to Normal Urine Specificity/Interference Level 1
| Sodium 40 mmol/l | Potassium 25 mmol/l | Chloride 110 mmol/l | |
|---|---|---|---|
| Haemoglobin | 590 mg/dl | 765 mg/dl | 1000 mg/dl |
| Total Bilirubin | 17.4 mg/dl | 60 mg/dl | 60 mg/dl |
| Conjugate Bilirubin | 22 mg/dl | 60 mg/dl | 44.5 mg/dl |
| Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| Intralipid® | 810 mg/dl | 2000 mg/dl | 2000 mg/dl |
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| Sodium 220 mmol/l | Potassium 125 mmol/l | Chloride 250 mmol/l | |
|---|---|---|---|
| Haemoglobin | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl |
| Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl |
| Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl |
| Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| Intralipid® | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
Table 15: Analytes Added to Normal Urine Specificity/Interference Level 2
Table 16: Exogenous Interferences in Urine - Level 1
| InterferingSubstance | Sodium 40 mmol/l | Potassium 25 mmol/l | Chloride 110 mmol/l |
|---|---|---|---|
| Ascorbic Acid | 200 mg/dl | 200 mg/dl | 200 mg/dl |
| Boric Acid | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl |
| Ethanol | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl |
| GammaGlobulin | 500 mg/dl | 500 mg/dl | 500 mg/dl |
| Glucose | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| HSA | 500 mg/dl | 500 mg/dl | 500 mg/dl |
Table 17: Exogenous Interferences Level 2 (Urine)
| InterferingSubstance | Sodium 220 mmol/l | Potassium 125 mmol/l | Chloride 250 mmol/l |
|---|---|---|---|
| Ascorbic Acid | 200 mg/dl | 200 mg/dl | 200 mg/dl |
| Boric Acid | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl |
| Ethanol | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl |
| Gamma Globulin | 500 mg/dl | 500 mg/dl | 500 mg/dl |
| Glucose | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl |
| HSA | 500 mg/dl | 500 mg/dl | 500 mg/dl |
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Method comparison with predicate device:
Correlation studies were carried out for serum and urine in accordance with C.L.S.I. guideline EP09c 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline- Third Edition'. A method comparison was conducted against the unmodified device (cleared under K052914) to confirm the device is substantially equivalent. Testing was conducted on two RX imola analysers, one RX imola analyser with the modified device, and the other RX imola analyser with the unmodified device.
Correlation (Serum)
Sodium
This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 1.06x - 8.4
R = 0.973
105 patient serum samples were analysed spanning the range 111.7 to 195.8 mmol/l.
Potassium
This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 1.02x - 0.09
R = 0.998
109 patient serum samples were analysed spanning the range 0.96 to 10.63 mmol/l.
Chloride
This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 1.03x - 6.59
R = 0.987
104 patient serum samples were analysed spanning the range 86.2 to 196.2 mmol/l.
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Correlation (Urine)
Sodium
This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 0.92x + 6.43
R = 0.997
72 patient urine samples were analysed spanning the range 49.4 to 298.6 mmol/l.
Potassium
This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 1.03x = 1.02
R = 0.999
84 patient urine samples were analysed spanning the range 9.5 to 167.6 mmol/l.
Chloride
This method - RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: -
Y = 0.89x + 18.49
R = 0.986
90 patient urine samples were analysed spanning the range 84.8 - 226.8 mmol/l.
DESIGN CONTROL ACTIVITIES
The verification and validation of the device modification has been performed under design control. The design control activities were based on the risk analysis and acceptance criteria were set to maintain the performance and safety of the device. The verification and validation includes in-house studies of precision, method comparison, interferences and linearity.
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RISK ANALYSIS
A Risk Analysis was performed to identify any new risks associated with the change in the ISE electrodes provided with the RX imola. Based on this and the testing the results indicate that the changes to the ISE unit on the RX imola are safe and effective for the stated intended use and are substantially equivalent to the previously approved device.
OVERALL CONCLUSION
The modified device is substantially equivalent to the unmodified device (cleared under K052914).
§ 862.1600 Potassium test system.
(a)
Identification. A potassium test system is a device intended to measure potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of diseases conditions characterized by low or high blood potassium levels.(b)
Classification. Class II.