(64 days)
The Synermed ISE Reagents are used for in-vitro diagnostic use to quantitate levels of Sodium, Potassium and Chloride in serum. This device is for use in clinical laboratories only. Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus and other diseases involving electrolyte imbalance. Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
The Synermed ISE reagents contain the following ingredients: Sodium Chloride, Potassium Chloride, Sodium Bicarbonate, Potassium Phosphate. The ISE buffer contains trlethanolamine preservatives 0.1M, phosphoric acid 0.3% and nonreactive preservatives. The ISE Mid-Standard contains sodium chloride 2.96mM, potassium chloride 0.12M, buffer and non-reactive preservatives. The ISE Reference contains 1M potassium chloride.
Here's a breakdown of the acceptance criteria and study information for the Synermed ISE Reagents, based on the provided FDA 510(k) summary:
1. Acceptance Criteria and Reported Device Performance
Device: Synermed ISE Reagents for Sodium, Potassium, and Chloride.
| Test Category | Analyte | Acceptance Criteria | Reported Device Performance (Summary) |
|---|---|---|---|
| Precision | Sodium | Within-Run %CV & Run-to-Run %CV less than Westgard requirements. | Achieved; all Within-Run and Run-to-Run %CVs for Sodium at various concentrations (81-180 mEq/L) were lower than the specified Westgard requirements (e.g., Target Conc. 135 mEq/L: Westgard Within-Run %CV Req = 0.6%, Actual = 0.05%; Westgard Run-to-Run %CV Req = 0.7%, Actual = 0.04%). |
| Potassium | Within-Run %CV & Run-to-Run %CV less than Westgard requirements. | Achieved; all Within-Run and Run-to-Run %CVs for Potassium at various concentrations (1.5-10 mEq/L) were lower than the specified Westgard requirements (e.g., Target Conc. 5.8 mEq/L: Westgard Within-Run %CV Req = 4.6%, Actual = 0.12%; Westgard Run-to-Run %CV Req = 5.6%, Actual = 0.1%). | |
| Chloride | Within-Run %CV & Run-to-Run %CV less than Westgard requirements. | Achieved; all Within-Run and Run-to-Run %CVs for Chloride at various concentrations (60-130 mEq/L) were lower than the specified Westgard requirements (e.g., Target Conc. 101 mEq/L: Westgard Within-Run %CV Req = 1.2%, Actual = 0.48%; Westgard Run-to-Run %CV Req = 1.5%, Actual = 0.43%). | |
| Linearity/Reportable | Sodium | Slope, Intercept, R² within acceptable limits. Claimed Measuring Range (80-180 mmol/L). | Slope: 0.9987, Intercept: 1.1021, R²: 0.9995. Sample Range Tested: 80-180 mmol/L. Claimed Measuring Range: 80-180 mmol/L. These values indicate good linearity across the claimed range. |
| Range | Potassium | Slope, Intercept, R² within acceptable limits. Claimed Measuring Range (1.5-10 mmol/L). | Slope: 1.0048, Intercept: 0.0237, R²: 0.9999. Sample Range Tested: 1.5-10 mmol/L. Claimed Measuring Range: 1.5-10 mmol/L. These values indicate good linearity across the claimed range. |
| Chloride | Slope, Intercept, R² within acceptable limits. Claimed Measuring Range (60-140 mmol/L). | Slope: 0.9814, Intercept: 1.3911, R²: 0.9998. Sample Range Tested: 60-140 mmol/L. Claimed Measuring Range: 60-140 mmol/L. These values indicate good linearity across the claimed range. | |
| Analytical Specificity | All | Analyte Target Concentration ≤ ± 10% bias in the presence of interfering substances. | No bias greater than 10% was observed for Sodium and Chloride with Hemoglobin (500mg/dL), Bilirubin (342umol/L), and Triglycerides (37mmol/L). No bias greater than 10% was observed for Potassium with Bilirubin (342umol/L) and Triglycerides (37mmol/L). Hemolysis is a known factor for high potassium and hemolyzed samples should not be used. Other exogenous substances referenced Young, et al. |
| Comparison Studies | All | High correlation coefficient, slope near 1, intercept near 0, and acceptable bias against predicate. | Comparison between Synermed IR-1200 and Hitachi 717 shows strong correlation: Sodium (r=0.992246, slope=0.990656, intercept=0.943789), Potassium (r=0.993021, slope=0.985861, intercept=-0.10291), Chloride (r=0.993346, slope=0.998305, intercept=0.122558). These values demonstrate good agreement with the predicate. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility: The tables show "80 results" for each analyte (Sodium, Potassium, Chloride) across various target concentrations. This implies a sample size of 80 measurements for each analyte to calculate precision metrics.
- Linearity/Reportable Range: The document lists "Sample Range Tested" for each analyte, indicating the range of control samples or diluted patient samples used to assess linearity. The exact number of discrete samples within these ranges is not specified beyond the range itself.
- Analytical Specificity: The document mentions testing "the following concentrations of endogenous substances" but does not specify the number of samples or replicates used for these interference studies.
- Comparison Studies: The document does not explicitly state the sample size (number of patient samples) used for the comparison study between the IR-1200 and Hitachi 717.
- Data Provenance: Not explicitly stated. The studies were conducted in accordance with CLSI/NCCLS guidelines, which are international standards, but the country of origin of the data or whether it was retrospective or prospective is not provided. Given these are in vitro diagnostic reagents, the data would likely be from laboratory testing rather than patient cohorts in the way typical of imaging studies.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This section is not applicable to this type of device. The Synermed ISE Reagents are in vitro diagnostic devices for quantitative measurement of electrolytes. The "ground truth" for these tests is established by reference methods or highly accurate laboratory instruments, not by expert human interpretation (e.g., radiologists interpreting images). The accuracy of the measurements is compared against known standards or predicate devices.
4. Adjudication Method
This section is not applicable as the device involves quantitative laboratory measurements rather than subjective interpretation requiring adjudication among experts. The performance is assessed through statistical analysis of numerical results against predefined criteria and reference methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This is not applicable. An MRMC study assesses the impact of AI on human readers' performance (e.g., diagnostic accuracy in interpreting medical images). This document is for in vitro diagnostic reagents, which do not involve human interpretation in the same manner.
6. Standalone Performance Study
Yes, the studies presented are primarily standalone (algorithm only without human-in-the-loop performance), as they evaluate the intrinsic performance characteristics of the reagents and their compatibility with the Synermed IR-1200 instrument.
- Precision/Reproducibility: This measures the inherent consistency of the device's measurements.
- Linearity/Reportable Range: This assesses the device's ability to accurately measure across its claimed concentration range.
- Analytical Specificity: This evaluates the device's resilience to common interfering substances.
- Comparison Studies: This evaluates the device's concordance with a predicate device.
These studies assess the direct analytical performance of the reagents.
7. Type of Ground Truth Used
The ground truth for evaluating the Synermed ISE Reagents is established through:
- Reference materials/standards: Used to set target concentrations for precision and linearity studies.
- Predicate device measurements: For the comparison studies, the results from the legally marketed predicate device (Synermed ISE Reagents using the Hitachi 717) serve as a comparative "ground truth" or reference for demonstrating substantial equivalence.
- Defined concentrations of interfering substances: For analytical specificity, known concentrations of substances like bilirubin, hemoglobin, and triglycerides are used.
8. Sample Size for the Training Set
This information is not provided. The document details performance testing for validation (test set), but does not discuss any "training set." This device is a chemical reagent product, not a machine learning or AI algorithm in the typical sense that would require a distinct training data set to "learn." Its performance is based on chemical and electrochemical principles.
9. How Ground Truth for the Training Set Was Established
This section is not applicable as no training set is discussed or implied for this type of in vitro diagnostic reagent.
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July 10, 2018
Infrared Laboratory Systems, LLC (dba Synermed) Julie Paschal Regulatory Affairs Specialist 17408 Tiller Court Suite 1900 Westfield. IN 40674
Re: K181201
Trade/Device Name: Synermed ISE Reagents Regulation Number: 21 CFR 862.1665 Regulation Name: Sodium test system Regulatory Class: Class II Product Code: JGS, CGZ, CEM Dated: February 27, 2018 Received: May 11, 2018
Dear Julie Paschal:
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. 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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
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Part 820); 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) K181201
Device Name Synermed ISE Reagents
Indications for Use (Describe)
The Synermed ISE Reagents are used for in-vitro diagnostic use to quantitate levels of Sodium, Potassium and Chloride in serum. This device is for use in clinical laboratories only. Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus and other diseases involving electrolyte imbalance. Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
| 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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510(k) Summary
K181201
1. Company Information
Infrared Laboratory Systems, LLC 17408 Tiller Court Suite 1900 Westfield, Indiana 46074 Telephone; (317) 896-1565 FAX: (317) 896-1566
2. Contact Information
Julie Paschal Regulatory Affairs Specialist Telephone: 336-235-3057 Email: jpaschal@slplabs.com
3. Date Prepared: July 2, 2018
4. Device Trade Name: Synermed ISE Reagents
5. Reagent Device Classification:
| ProCode | ClassificationRegulation | Classification Name | Device Class | Panel |
|---|---|---|---|---|
| JGS | 862.1665 | Sodium test system | Class II | 75 |
| CEM | 862.1600 | Potassium test system | Class II | 75 |
| CGZ | 862.1170 | Chloride test system | Class II | 75 |
6. Identification of Predicates:
| K-number | Manufacturer | Trade Name | Method |
|---|---|---|---|
| K952179 | Synermed | SynermedISEReagents | Ion SelectiveElectrode |
7. Device Description
The Synermed ISE reagents contain the following ingredients: Sodium Chloride, Potassium Chloride, Sodium Bicarbonate, Potassium Phosphate. The ISE buffer contains trlethanolamine preservatives 0.1M, phosphoric acid 0.3% and nonreactive preservatives. The ISE Mid-Standard contains sodium chloride 2.96mM, potassium chloride 0.12M, buffer and non-reactive preservatives. The ISE Reference contains 1M potassium chloride.
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8. Substantial Equivalence
| Items | Candidate Device: | Predicate Device: |
|---|---|---|
| Synermed ISE ReagentsK181201 | Synermed ISE ReagentsK952179 | |
| Similarities | ||
| Intended Use | Quantitative Measurementof Sodium, Potassium andChloride in serum | Same |
| Environment | Clinical Laboratory UseOnly | Same |
| Specimen | Serum | Same |
| Differences | ||
| For use with | Synermed IR-1200 | Hitachi 717 |
9. Intended Use
ISE Reagents
The Synermed ISE reagents are intended for the in vitro quantitative measurement of sodium, potassium, and chloride in serum. This device is for use in clinical laboratories only. Sodium measurements are used in the diagnosis and treatment of aldosteronism, diabetes insipidus and other diseases involving electrolyte imbalance. Potassium measurements are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
10. Summary of Performance Testing
a. Precision/Reproducibility
Testing for Precision was accomplished by following the procedures and protocols outlined in the CLSI EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition, and in NCCLS EP15-A2 User Verification of Performance for Precision and Trueness; Approved Guideline - Second Edition
Results: Data Examination - NCCLS document EP15-A2; Section 8 pp. 6-10.
Precision Data Analysis Section Figure 1.1 - Mean, Standard Deviation & %CV for all 80 Results for Sodium
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| TargetConcentrationof Sodium inmEq/L | ActualMeaninmEq/L | Westgard%CV WithinRunRequirement | WithinRun%CV | WithinRunSD | %CVPass(Y/N) | Westgard%CV Run toRunRequirement | Run toRun%CV | Run toRunSD | %CVPass(Y/N) |
|---|---|---|---|---|---|---|---|---|---|
| 81 | 81.1 | 0.05 | 0.04 | Y | 0.04 | 0.03 | Y | ||
| 115 | 114.87 | 0.06 | 0.07 | Y | 0.05 | 0.06 | Y | ||
| 135 | 134.97 | 0.6 | 0.05 | 0.06 | Y | 0.7 | 0.04 | 0.06 | Y |
| 150 | 150.02 | 0.06 | 0.09 | Y | 0.05 | 0.07 | Y | ||
| 180 | 181.05 | 0.07 | 0.13 | Y | 0.07 | 0.12 | Y |
Figure 1.2 - Mean, Standard Deviation & %CV for all 80 Results for Potassium
| Potassium Precision Data Summary Table | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| TargetConcentrationof Potassiumin mEq/L | ActualMeaninmEq/L | Westgard%CV WithinRunRequirement | WithinRun%CV | WithinRunSD | %CVPass(Y/N) | Westgard%CV Run toRunRequirement | Run toRun%CV | Run toRunSD | %CVPass(Y/N) |
| 1.5 | 1.49 | 0.52 | 0.01 | Y | 0.37 | 0.01 | Y | ||
| 3.0 | 2.98 | 0.22 | 0.01 | Y | 0.19 | 0.01 | Y | ||
| 5.8 | 5.79 | 4.6 | 0.12 | 0.01 | Y | 5.6 | 0.1 | 0.01 | Y |
| 7.5 | 7.49 | 0.11 | 0.01 | Y | 0.09 | 0.01 | Y | ||
| 10.0 | 10.04 | 0.58 | 0.06 | Y | 0.46 | 0.05 | Y |
Figure 1.3 - Mean, Standard Deviation & %CV for all 80 Results for Chloride
| Chloride Precision Data Summary Table | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| TargetConcentrationof Chloride inmEq/L | ActualMeaninmEq/L | Westgard%CV WithinRunRequirement | WithinRun%CV | WithinRunSD | %CVPass(Y/N) | Westgard%CV Run toRunRequirement | Run toRun%CV | Run toRunSD | %CVPass(Y/N) |
| 60 | 60.22 | 0.52 | 0.31 | Y | 0.48 | 0.29 | Y | ||
| 90 | 90.08 | 0.1 | 0.09 | Y | 0.07 | 0.07 | Y | ||
| 101 | 100.77 | 1.2 | 0.48 | 0.49 | Y | 1.5 | 0.43 | 0.43 | Y |
| 112 | 112 | 0.08 | 0.09 | Y | 0.06 | 0.06 | Y | ||
| 130 | 129.98 | 0.06 | 0.08 | Y | 0.05 | 0.48 | Y |
Acceptance Criteria
- The Within-Run Precision and Within-Laboratory Precision results should be less than ● the noted requirements from Westgard for percent imprecision.
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b. Linearity/Reportable Range
Linearity
Testing for Linearity and Random Error was accomplished by following the procedures and protocols outlined in the NCCLS document EP6-A, Vol. 23, No. 16; Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline
QC samples will be performed before daily testing AND with each run. QC results must be within the established range before testing can begin.
| Measurand (inmmol/L) | Slope | Intercept | R2 | Sample RangeTested (inmmol/L) | Claimed MeasuringRange (in mmol/L) |
|---|---|---|---|---|---|
| Sodium | 0.9987 | 1.1021 | 0.9995 | 80-180 | 80-180 |
| Potassium | 1.0048 | 0.0237 | 0.9999 | 1.5-10 | 1.5-10 |
| Chloride | 0.9814 | 1.3911 | 0.9998 | 60-140 | 60-140 |
Linearity Results:
c. Analytical Specificity
Interfering Substances
Testing for Interference was accomplished by following the procedures and protocols outlined in the CLSI document EP07-A2; Interference Testing in Clinical Chemistry; Approved Guideline; Second Edition.
The following concentrations of endogenous substances were shown not to interfere with Sodium and Chloride. Hemoglobin- 500mg/dL Bilirubin (conjugated and unconjugated)- 342umol/L Triglycerides- 37mmol/L
The following concentrations of endogenous substances were shown not to interfere with Potassium. Bilirubin (conjugated and unconjugated)- 342umol/L Triglycerides- 37mmol/L
Acceptance Criteria - Analyte Target Concentration ≤ ± 10% bias.
No bias was seen to be greater than 10%, thus all potential endogenous substance interference is considered to be within acceptable range. Hemolysis is a known contributing factor to abnormally high potassium levels, therefore hemolyzed samples should not be used. Other exogenous substances studies will be referenced to studies done by Young, et al.
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d. Comparison Studies
Testing for Comparisons and Bias was accomplished by following the procedures and protocols outlined in the CLSI document EP09-A3; Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition.
Data Examination
- a. Visual examination of the data is performed to look for outliers.
- b. A correlation coefficient was calculated for each analyte.
- c. Slope and Intercept were also calculated for each analyte.
Table 2.1 - IR-1200 and Hitachi 717 Comparison Study Data Summary
| Sodium | |
|---|---|
| Correlation Coefficient | 0.992246 |
| Slope | 0.990656 |
| Intercept | 0.943789 |
| Potassium | |
| Correlation Coefficient | 0.993021 |
| Slope | 0.985861 |
| Intercept | -0.10291 |
| Chloride | |
| Correlation Coefficient | 0.993346 |
| Slope | 0.998305 |
| Intercept | 0.122558 |
11. Conclusions
The new device is substantially equivalent to the predicate because it has the same intended use and has the same or similar technological characteristics that do not raise new types of questions of safety and effectiveness.
§ 862.1665 Sodium test system.
(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.