EPOC CHLORIDE TEST AND EPOC CREATININE TEST
Device Facts
| Record ID | K113726 |
|---|---|
| Device Name | EPOC CHLORIDE TEST AND EPOC CREATININE TEST |
| Applicant | Epocal, Inc. |
| Product Code | CGL · Clinical Chemistry |
| Decision Date | Oct 5, 2012 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1225 |
| Device Class | Class 2 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K113726 · Oct 5, 2012 | EPOC CHLORIDE TEST AND EPOC CREATININE TEST | Epocal, Inc. | Hospital clinical field trials; Patient whole blood samples (venous, arterial, capillary) | Clinical field trials were conducted at hospital sites to evaluate the method comparison and precision of the epoc Chloride and Creatinine tests when used by trained medical professionals in a point-of-care environment. | Method comparison; Point-of-care; Clinical field trials; Whole blood samples |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Clinical field trials; Method comparison study | Patients requiring chloride or creatinine testing; Sample Size: 155 (Chloride), 144 (Creatinine); Number of Sites: 2 hospitals | Abbott i-STAT 300, Roche Cobas 6000, and other serum-based laboratory methods | Method comparison (slope, intercept, R2, bias) |
| Clinical site precision study; Precision study in clinical setting | Patient samples (normal and spiked); Sample Size: Multiple replicates per user; Number of Sites: 3 sites | Not applicable for this study | Precision (SD, %CV) |
Indications for Use
The Creatinine test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care. Creatinine measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal diseases and in monitoring renal dialysis. The Chloride test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care. Chloride measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of electrolyte and metabolic disorders.
Device Story
The epoc Blood Analysis System is a point-of-care (POC) diagnostic platform consisting of a reader and single-use test cards. This submission adds chloride and creatinine sensors to the existing card. The user inserts the card into the reader, which automatically performs calibration, heats the measurement region to 37°C, and opens fluidic valves. The user introduces a whole blood sample; sensors generate electrical signals proportional to analyte concentrations. Data is transmitted wirelessly to an epoc Host (mobile computing device) for display and storage. The system calculates additional values including Anion Gap and eGFR (MDRD type). Results assist clinicians in diagnosing electrolyte/metabolic disorders and renal disease. The system is intended for use by trained medical professionals in clinical settings.
Clinical Evidence
Clinical field trials were conducted at two hospitals comparing the epoc System against predicate and comparative devices using venous, arterial, and capillary whole blood samples. Method comparison for chloride (N=155 vs. i-STAT) showed R²=0.98 and mean bias of -1.0 mM at 112 mM. Creatinine comparison (N=144 vs. Roche Cobas) showed R²=0.99 and mean bias of -0.06 mg/dL at 1.25 mg/dL. Precision studies (aqueous and whole blood) were performed across multiple sites by various end-users (RNs, technicians, phlebotomists), demonstrating acceptable CV% across clinical ranges.
Technological Characteristics
Unit-use test card with fluidic housing, electrochemical multi-sensor array, and on-board calibration fluid. Chloride: ion-selective electrode. Creatinine: three-layer enzyme electrode (Creatinine Amidohyrdolase, Creatine Amidinohydrolase, Sarcosine Oxidase) with gold electrode. Measurement temperature 37°C. Connectivity: epoc Blood Analysis System reader. Software: embedded application for signal processing and e-GFR calculation.
Indications for Use
Indicated for trained medical professionals to perform quantitative testing of chloride and creatinine in heparinized or un-anticoagulated arterial, venous, or capillary whole blood. Used for diagnosis/treatment of renal diseases, monitoring renal dialysis, and managing electrolyte/metabolic disorders.
Regulatory Classification
Identification
A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Predicate Devices
- i-Stat™ Chloride using i-Stat™ Model 300 Portable Clinical Analyzer (K001387)
- Roche Cobas c 511/512 CREP2 Creatinine Plus ver. 2 assay (K024098)
Submission Summary (Full Text)
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SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
k113726
B. Purpose for Submission:
Addition of Creatinine and Chloride tests to a previously cleared device, the epoc Blood Analysis System
C. Measurand:
Creatinine and Chloride
D. Type of Test:
Quantitative, electromechanical biosensor;
Enzyme-cascade amperometric peroxide detection for creatinine;
Ion selective electrode for chloride
E. Applicant:
Epocal Inc.
F. Proprietary and Established Names:
epoc™ Creatinine Test
epoc™ Chloride Test
G. Regulatory Information:
1. Regulation section:
21 CFR 862.1225; Creatinine test system
21 CFR 862.1170; Chloride test system
2. Classification:
Class II
3. Product code:
CGL for creatinine and CGZ for chloride
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4. Panel:
Clinical Chemistry (75)
H. Intended Use:
1. Intended use(s):
See Indication for Use below
2. Indication(s) for use:
The Creatinine test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care.
Creatinine measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal diseases and in monitoring renal dialysis.
The Chloride test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care.
Chloride measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of electrolyte and metabolic disorders.
3. Special conditions for use statement(s):
For prescription use and Point-of-Care use
For in vitro diagnostics use only
4. Special instrument requirements:
epoc Blood Analysis System
I. Device Description:
The single use epoc blood test card is comprised of
a) a bar-coded credit-card sized fluidic housing, b) a sample entry port for the introduction of a blood sample, c) an array of sensors on a sensor module embedded in the housing and d) an on-board calibration fluid (~115 ul) contained within a sealed reservoir. The calibration fluid contains the analytes with concentrations in the clinical decision levels; for creatinine and chloride, the concentration is 1.03 mg/dL and 95 mM respectively.
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The single use epoc blood test card contains the sensors, reagents, calibration fluids altogether in an individually packed cartridge to be inserted into the epoc Blood Analysis instrument for testing. There is no separate calibration step to be performed by the user.
The epoc Chloride and Creatinine tests are being added as additional sensors to the existing single use test card that is used with the epoc Blood Analysis System. The epoc Blood Analysis System with BGE test card was first cleared in k061597, the glucose and lactate tests were added with clearance of k090109 and k093297 respectively.
The addition of the epoc Chloride and Creatinine tests comprises four changes to the epoc System:
1. Addition of the new sensors on the test card;
2. Modification of the epoc System software application to accommodate the new tests;
3. Labeling changes including indications for use.
4. A built-in function to calculate estimated GFR(e-GFR) using the measured Creatinine value.
# J. Substantial Equivalence Information:
1. Predicate device name(s):
i-STAT™ Chloride and Creatinine Tests using i-STAT™ Model 300 Portable Clinical Analyzer
2. Predicate 510(k) number(s):
k001387
3. Comparison with predicate:
| Similarities and Differences | | |
| --- | --- | --- |
| Characteristics | Proposed device: k113726 epocTM Creatinine Test and epocTM Chloride Test using epoc Blood Analysis System | Predicate device: k001387 i-STATTM Chloride and Creatinine Tests using i-STATTM Model 300 Portable Clinical Analyzer |
| Intended Use /Indications for use | Intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of chloride and creatinine | Same |
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| | in the laboratory or at the point of care.
Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders.
Creatinine measurements are used in the diagnosis and treatment of certain renal diseases and in monitoring renal dialysis. | |
| --- | --- | --- |
| Measured Parameters | pH, pCO2, pO2, Na, K, iCa, Cl, Hct, Gluc, Lact, Crea | Same |
| Test Card | Unit-use card with
- on-board calibrator in sealed reservoir
- an electrochemical multi-sensor array
- port for sample introduction
- fluid waste chamber | Same |
| Sample Type | Venous, arterial and capillary whole blood | Same |
| Sample volume | 92 ul | 100 ul |
| Tests/sensor components | Cl – ion selective electrode
Crea - enzyme-cascade amperometric peroxide detection | Same |
| Measuring temperature | 37°C | Same |
| Reportable ranges | Cl 65 – 140 mM
Crea 0.3 – 15.0 mg/dL
eGFR* Numeric values reported between 2- 60 mL/m/1.73 m²; calculated values >60 are reported as > 60 mL/m/1.73 m² | Cl 65 – 140 mM
Crea 0.2 – 20.0 mg/dL
Normal ranges vary with the equations used for the e-GFR calculations. |
| Test Card Storage | Room temperature until expiry date | Store refrigerated until expiration date including maximum 2 weeks at room temperature |
| Calculated Parameters | TCO2, HCO3, BE, sO2,Hgb, AGAP, eGFR | TCO2, HCO3, BE, sO2,Hgb, AGAP |
| Measurement time | 35sec from sample introduction | 200 sec from sample introduction |
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* e-GFR reporting is based on the most recent recommendation from National Kidney Foundation Kidney Disease Education Program. The sponsor has the following limitation in the labeling:
eGFR >60 does not exclude the possibility of mild renal disease. Further laboratory testing may be necessary to distinguish normal renal function from mild renal disease.
## K. Standard/Guidance Document Referenced:
IEC 60601-1 Medical Electrical Equipment - Part 1: General Requirements for Safety, 1988; Amendment 1, 1991-11, Amendment 2, 1995. (General)
IEC 60601-1-2 Medical Electrical Equipment - Part 1-2: General Requirements for Safety - Collateral Standard: Electromagnetic Compatibility - Requirements and Tests, 2001
ISO 14971 Medical devices - Application of risk management to medical devices, 2007
CLSI EP09-A2 Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline, 2004
CLSI EP07-A2 Interference Testing in Clinical Chemistry, 2005
CLSI EP06-A Evaluation of the Linearity of Quantitative Measurement, 2003
CLSI EP05-A2 Evaluation of Precision Performance of Clinical Chemistry Devices, 2004
CLSI EP17-A Protocols for Determination of Limits of Detection and Limits of Quantization
## L. Test Principle:
Ion-selective electrode is used for the chloride measurement. Chloride measurement is based on the potential difference between the electrode pair (sample versus a reference electrode) follows the modified Nernst equation (Nickolsky equation). The measurement is performed by a high input impedance operational amplifier in the card reader connected to each of the membrane coated sensor electrode pairs comprising sensor electrode and reference electrode. ΔV, the potential difference between sample and the calibrator is proportional to the concentration difference of chloride in the sample and calibrator.
The creatinine sensor comprises a three (3) layer enzyme electrode. The main reaction layer uses the enzymes Creatinine Amidohyrdolase, Creatine Amidinohydrolase and Sarcosine Oxidase to convert creatinine to hydrogen peroxide; which is subsequently detected by redox-mediated horseradish-peroxidase (HRP)-catalyzed reduction on a gold electrode. In the creatinine electrode screening layer, the background creatine is converted to water and oxygen and the outer diffusion barrier facilitates rapid transport of oxygen to the oxidase enzyme to assure the sensor response is linear and proportional to the concentration of creatinine in the test fluid.
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This device provides eGFR calculations using the obtained creatinine results. The equations (shown below) used in this device are IDMS-traceable and derived from Modification of Diet in Renal Disease (MDRD) study.
$$
\mathrm {e G F R} = 1 7 5 \mathrm {x} (\text {C r e a - 1 . 1 5 4}) \mathrm {x} (\text {A g e - 0 . 2 0 3}) \mathrm {x} (0. 7 4 2 \text {i f f e m a l e , 1 i f m a l e}) \text {f o r}
$$
Caucasians;
$$
\mathrm {e G F R - a} = 1 7 5 \mathrm {x} (\text {C r e a - 1 . 1 5 4}) \mathrm {x} (\text {A g e - 0 . 2 0 3}) \mathrm {x} (0. 7 4 2 \text {i f f e m a l e , 1 i f m a l e}) \mathrm {x} 1. 2 1 2 \text {f o r}
$$
African Americans
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
**In-house precision:**
This twenty day precision using two levels of aqueous controls followed the CLSI guideline EP5-A2. The measurements were taken using 2 runs a day in duplicate using 3 lots of test cards. The total precision results are shown in the table below:
| Analytes | Chloride (mM) | | Creatinine (mg/dL) | |
| --- | --- | --- | --- | --- |
| AQ Controls | L1 | L3 | L1 | L3 |
| Numbers tested (n) | 240 | 240 | 239 | 241 |
| Mean | 76.9 | 125.0 | 0.71 | 5.50 |
| SD | 0.39 | 0.86 | 0.035 | 0.226 |
| CV (%) | 0.5 | 0.7 | 4.9 | 4.1 |
### POC precision:
An additional precision study was performed by intended users at multiple point-of-care sites (3 for creatinine and 4 for chloride) with multiple POC operators following the CLSI guideline EP5-A2.
i. The aqueous control precision study was performed using three levels of commercially available controls. For each level of control, each operator ran 15 test cards (from a minimum of 3 lots) on 5 readers. Within-run precision
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and total precision results were shown in the table below:
| Chloride | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| AQ Controls | L1 | | L2 | | L3 | |
| | Within Run | Total | Within Run | Total | Within Run | Total |
| Numbers tested (n) | 15 | 165 | 11 | 163 | 10 | 148 |
| Mean (mM) | 76.5 | 76.5 | 98.6 | 98.6 | 123.7 | 123.7 |
| SD | 0.44 | 0.50 | 0.44 | 0.56 | 0.69 | 1.06 |
| CV(%) | 0.6 | 0.7 | 0.4 | 0.6 | 0.6 | 0.9 |
| Creatinine | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| AQ Controls | L1 | | L2 | | L3 | |
| | Within Run | Total | Within Run | Total | Within Run | Total |
| Numbers tested(n) | 8 | 120 | 8 | 119 | 8 | 120 |
| Mean (mg/dL) | 0.66 | 0.66 | 2.04 | 2.04 | 4.31 | 4.31 |
| SD | 0.04 | 0.05 | 0.08 | 0.13 | 0.21 | 0.27 |
| CV(%) | 6.1 | 6.8 | 3.8 | 6.4 | 4.8 | 6.3 |
ii. A whole blood precision study was performed using freshly collected blood samples. Each operator ran 10 test cards (from a minimum of 3 lots) on 10 readers $(N = 10)$ . Two tube types, syringe and capillary tubes were evaluated in all the POC sites. Each level of syringe samples was run by 12 operators and each level of capillary samples was run by 4 operators. Within-run precision for each individual operator was calculated. The results of a representative POC operator from each site are shown in the table below:
| Chloride | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | WB | Tube | | | | |
| Site | User | Level | type | N | Mean | SD | %CV |
| Sample | 1 | 1 | 1 | 1 | 1.00 | 0.00 | 0.00 |
| Sample | 2 | 2 | 2 | 2 | 1.00 | 0.00 | 0.00 |
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| 1 | Operator 1 | Level 1 | syringe | 10 | 102.11 | 1.01 | 1.0 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | Operator 2 | Level 1 | syringe | 10 | 102.58 | 0.53 | 0.5 |
| 2 | Operator 1 | Level 2 | syringe | 10 | 107.43 | 0.34 | 0.3 |
| 2 | Operator 2 | Level 2 | syringe | 10 | 105.81 | 0.39 | 0.4 |
| 3 | Operator 1 | Level 3 | capillary | 10 | 131.32 | 2.10 | 1.6 |
| 3 | Operator 2 | Level 3 | capillary | 10 | 132.02 | 1.11 | 0.8 |
| Creatinine | | | | | | | |
| Site | User | WB Level | Tube type | N | Mean | SD | %CV |
| 1 | Operator 1 | Level 1 | Syringe | 9 | 0.64 | 0.03 | 5.3 |
| 1 | Operator 2 | Level 1 | Syringe | 9 | 0.63 | 0.05 | 8.1 |
| 2 | Operator 1 | Level 2 | Capillary | 10 | 1.42 | 0.07 | 5.1 |
| 2 | Operator 2 | Level 2 | Capillary | 10 | 1.43 | 0.05 | 3.4 |
| 3 | Operator 1 | Level 3 | Syringe | 10 | 0.48 | 0.04 | 8.8 |
| 3 | Operator 2 | Level 3 | syringe | 10 | 0.43 | 0.02 | 3.6 |
# b. Linearity/assay reportable range:
The linearity study was performed in-house using lithium heparin whole blood samples based on the CLSI EP6-A recommendations for evaluation of linearity. Blood samples with analyte concentrations spanning the entire measuring range were prepared starting with pooled blood. Contrived samples were used at lower ends of the measuring ranges. Analyte concentrations were evaluated versus an in-house FDA-cleared method with traceability to NIST standards. Regression analysis was performed as per CLSI EP6-A.
The regression analysis of the linearity data is shown below:
Chloride linearity
| Test range | Slope | Intercept | R2 |
| --- | --- | --- | --- |
| 65-144 mM | 0.968 | 3.08 | 0.999 |
Creatinine linearity
| Test range | Slope | Intercept | R2 |
| --- | --- | --- | --- |
| 0.25 – 15.5 mg/dL | 1.00 | 0.07 | 0.9996 |
Based on the results of the linearity study, the sponsor claimed that the chloride test has a measuring range of 65 to $140\mathrm{mM}$ (mmol/L) and the creatinine test has a measuring range of 0.3 to $15\mathrm{mg/dL}$ .
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
# Traceability:
Chloride ion concentration values assigned to the calibrator fluids are traceable to NIST standards.
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Creatinine concentration values assigned to the calibrator fluids are traceable to NIST standard SRM 967. The epoc Creatinine test is calibrated to an IDMS-traceable whole blood method and reports plasma equivalent concentrations.
## Calibrators (calibration fluid) stability:
Calibration fluid stability study protocol and acceptance criteria has been provided and found to be adequate. The sponsor claimed that the shelf-life of the test card with the sensor and calibration fluid is 18 months at room temperature.
## d. Detection limit:
The study was performed in-house as per CLSI EP6-A recommendations for evaluation limits of detection and quantification. Limits of Blank (LoB) and Detection (LoD) were obtained for both chloride and creatinine. To ensure the reliability of creatinine measurement at the low end, a Limit of Quantification (LoQ) study was performed with contrived whole blood samples. LoB was based on 125 replicates of measurements for chloride and 69 replicates of measurements for creatinine. LoD was calculated according to the formula $\mathrm{LoB} + 1.645\mathrm{SD}$ . For creatinine, LoQ was based on total 240 measurements of 3 low samples with an inter-assay precision of $15\%$ . The detection limits study results are summarized below:
| Analyte | LoB | LoD | LoQ |
| --- | --- | --- | --- |
| Creatinine [mg/dL] | 0.16 | 0.3 | 0.3 |
| Chloride [mM] | 55.65 | 56.74 | Not performed |
The sponsor claimed that the low end of the reportable range for the epoc chloride test is $65\mathrm{mM}$ and the epoc creatinine test is $0.30\mathrm{mg/dL}$ .
## e. Analytical specificity:
An interference study was performed based on the CLSI "Interference Testing in Clinical Chemistry; Approved Guideline", CLSI document EP7-A2. The interference study was performed in-house on the epoc Chloride and Creatinine sensors. The test sample was spiked by addition of interference substances, while the control sample was spiked by the addition of the solvent of the interference substances. Two levels of analyte concentrations were tested with different levels of interference substances. All samples were tested in replicates of six. The concentration of interfering substance considered as causing no clinically significant interference is defined as a bias (difference between the test and the control sample) of:
$\leq 0.2 \mathrm{mg} / \mathrm{dL}$ for creatinine concentrations $\leq 2 \mathrm{mg} / \mathrm{dL}$ and $\leq 7.9\%$ for creatinine
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concentrations >2 mg/dL;
4.2% for chloride concentrations ≤125 mM and ≤5.2% for chloride concentrations >125 mM.
## Summary of interference studies for Chloride:
i) Exogenous interferences were tested and found to be clinically non-significant:
| Interferent | Test Level mg/dL | Interferent | Test Level mg/dL |
| --- | --- | --- | --- |
| Acetaminophen | 20 | Glutathione | 156 |
| Acetylsalicylic acid | 65.2 | Hydroxyurea | 6.96 |
| Ascorbate (Na) | 6.8 | Intralipid | 800 |
| Dobutamine | 0.1 | Isonazid | 4 |
| Dopamine | 0.1 | L-Dopa | 2 |
| EDTA | 0.1 | Lidocaine | 1.2 |
| Ethanol | 400 | Methyldopa | 800 |
| Fluoride | 0.44 | Pentathol (Na) | 9.4 |
| Formaldehyde | 0.4 | Guaiacol | 5 |
| Glucose | 990 | Heparin | 3000 U/L |
| Iodide | 38 | Tolbutamide | 38 |
ii) Endogenous interferences were tested and found to be clinically non-significant:
| Interferent | Test Level mg/dL | Interferent | Test Level mg/dL |
| --- | --- | --- | --- |
| Bilirubin Conjugate | 26.8 | Protein (High) | 8 g/dL |
| Bilirubin | 20.1 | Protein (Low) | 6 g/dL |
| CO2 (High) | 102 mmHg | Lactate | 74 |
| CO2 (Low) | 13 mmHg | O2 (High) | 122 mmHg |
| Biocarbonate | 405 | O2 (Low) | 28 mmHg |
| Creatine | 5 | Sarcosine | 0.01 |
| Hematocrit (High) | 64 % | Urea | 258 |
| Hematocrit (Low) | 24 % | Uric Acid | 23.5 |
| pH (High) | >8.0 | Proline | 2.9 |
| pH (Low) | <6.8 | | |
iii) Clinically significant interferences for chloride are itemized below:
- β-Hydroxybutyrate: no significant effect up to 6.46 mM (67.2 mg/dL) after which it will increase the chloride reading by up to 0.06 mM per mg/dL
- Bromide: no significant effect up to 3.43 mM (27.4 mg/dL) after which it will increase the chloride reading up to 9.36 mM/mM Bromide
- Citrate: no significant effect up to 2.36 mM (45.3 mg/dL) after which it will increase the chloride reading by up to 0.12 mM per mg/dL Citrate
- N-Acetylcysteine: no significant effect up to 2.85 mM (46.4 mg/dL) after which it will decrease the chloride reading by up to 0.06 mM per mg/dL N-Acetylcysteine
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- Salicylate: no significant effect up to 2.54 mM (41.1 mg/dL) after which it will increase the chloride reading up to 0.03 mM per mg/dL salicylic acid
- Thiocyanate: no significant effect up to 2.50 mM (14.5 mg/dL) after which it will increase the chloride reading up to 0.04 mM per mg/dL Thiocyanate
Summary of interference studies for Creatinine:
iv) Exogenous interferences were tested and found to be clinically non-significant:
| Interferent | Test Level mg/dL | Interferent | Test Level mg/dL |
| --- | --- | --- | --- |
| Acetaminophen | 20 | Glutathione | 156 |
| Acetylsalicylic acid | 65.2 | Hydroxyurea | 6.96 |
| Ascorbate (Na) | 6.8 | Intralipid | 800 |
| Dobutamine | 0.1 | Isonazid | 4 |
| Dopamine | 0.1 | L-Dopa | 2 |
| EDTA | 0.1 | Lidocaine | 1.2 |
| Ethanol | 400 | Methyldopa | 800 |
| Fluoride | 0.44 | Pentathol (Na) | 9.4 |
| Formaldehyde | 0.4 | Guaiacol | 5 |
| Glucose | 990 | Heparin | 3000 U/L |
| Salicylate | 70 | Tolbutamide | 38 |
v) Endogenous interferences were tested and found to be clinically non-significant:
| Interferent | Test Level mg/dL | Interferent | Test Level mg/dL |
| --- | --- | --- | --- |
| Bilirubin | 20.1 | Protein | 8 g/dL |
| CO2 (High) | 102 mmHg | Protein | 6 g/dL |
| CO2 (Low) | 13 mmHg | Lactate | 74 |
| Biocarbonate | 405 | O2 (High) | 122 mmHg |
| Creatine | 5 | O2 (Low) | 28 mmHg |
| Hematocrit (High) | 64 % | Sarcosine | 0.01 |
| Hematocrit (Low) | 24 % | Urea | 258 |
| pH (High) | >8.0 | Uric Acid | 23.5 |
| pH (Low) | <6.8 | Proline | 2.9 |
| β-Hydroxybutyrate | 104 | | |
vi) Clinically significant interferences for creatinine are itemized below:
- Creatine: no significant effect up to 113 uM (1.52 mg/dL) after which it will increase the creatinine reading by up to 0.0025 mg/dL creatinine per uM creatine.
- Bilirubin: no significant effect up to 105 uM (8.76 mg/dL) after which it will increase the creatinine reading up to 0.002 mg/dL creatinine per uM bilirubin conjugate.
- Bromide: no significant effect up to 17.9 mM (143 mg/dL) after which it will increase the creatinine reading by up to 0.014 mg/dL creatinine per
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mM bromide.
- Thiocyanate: no significant effect up to $0.93\mathrm{mM}$ $(5.41\mathrm{mg / dL})$ after which it will decrease the creatinine reading by up to $0.142\mathrm{mg / dL}$ creatinine per mM thiocyanate.
- Citrate: no significant effect up to $19.9\mathrm{mM}$ $(382.1\mathrm{mg / dL})$ after which it will increase the creatinine reading up to $0.026\mathrm{mg / dL}$ creatinine per mM citrate.
- Iodide: no significant effect up to $0.007\mathrm{mM}$ $(0.089\mathrm{mg / dL})$ after which it will increase the creatinine reading up to $28\mathrm{mg / dL}$ creatinine per mM iodide.
- N-Acetylcysteine: no significant effect up to $820~\mathrm{uM}$ (13.35 mg/dL) after which it will decrease the creatinine reading up to $0.26\mathrm{mg / dL}$ per mmol/L N-Acetylcysteine. It has been reported that 1 mM N-acetyl cysteine is therapeutically unattainable in plasma. The therapeutic level for N-acetylcysteine is $0.3\mathrm{mM}$ .
f. Assay cut-off:
Not applicable
# 2. Comparison studies:
a. Method comparison with predicate device:
Method comparison studies were performed at a minimum of 3 POC sites by phlebotomist or similar point of care operators with the predicate devices (Abbott i-STAT for chloride and Roche Cobas for creatinine). Venous, arterial and capillary patient samples were compared with a whole blood point-of-care system. Venous samples were tested at site 1; arterial samples were tested at sites 2 and 3; capillary samples were tested at sites 2 and 3. The results of the overall performance of the device at all the sites are summarized in the table below:
| | Chloride | Creatinine |
| --- | --- | --- |
| Comparison to | Abbott i-STAT | Roche Cobas |
| N | 155 | 144 |
| slope | 0.99 | 1.03 |
| intercept | 0.2 | -0.10 |
| Xmin | 69 | 0.3 |
| Xmax | 139 | 14.8 |
| R2 | 0.98 | 0.99 |
| Ranges of samples tested | 69 – 139 mM | 0.3 -14.8 mg/dL |
Separate regression analysis on different specimen types (i.e. venous, arterial and capillary specimens) were performed and the results are summarized in the tables below:
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Data summary for Chloride (epoc vs i-STAT)
Linear regression:
| POC site | Site 1 | Sites 2 and 3 | Sites 2 and 3 |
| --- | --- | --- | --- |
| Specimen types | Venous | Arterial | Capillary |
| N | 49 | 43 | 63 |
| slope | 1.00 | 0.96 | 1.02 |
| intercept | -0.24 | 2.35 | -3.06 |
| test range | 72 - 136 | 69 - 136 | 70 -139 |
| R² | 0.97 | 0.99 | 0.99 |
Data summary for Creatinine (epoc vs Roche Cobas)
Linear regression:
| POC site | Site 1 | Sites 2 and 3 | Sites 2 and 3 |
| --- | --- | --- | --- |
| Specimen types | Venous | Arterial | Capillary |
| N | 53 | 42 | 49 |
| slope | 1.03 | 1.04 | 1.03 |
| intercept | -0.12 | -0.11 | -0.10 |
| test range | 0.30 – 14.5 | 0.30 -14.3 | 0.30 – 14.8 |
| R² | 0.99 | 0.99 | 0.99 |
b. Matrix comparison:
The sponsor has performed a comparison between un-anticoagulated blood and heparinized (lithium heparin) blood for creatinine and chloride; the results of the linear regression are shown in the table below:
| Analyte | Chloride | Creatinine |
| --- | --- | --- |
| N | 76 | 77 |
| slope | 0.98 | 0.99 |
| intercept | 1.92 | 0.02 |
| test range | 99-129 | 0.42 -10.53 |
| R² | 0.97 | 0.99 |
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
{13}
Not applicable
4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
Reference range for chloride is 98 - 107 mM (mEq/L)¹;
reference range for creatinine is 0.51 - 1.19 mg/dL (or 45 ~ 105 mM)²
1. From Reference Table 56-1 in Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 4th ED Elsevier Saunders, 2006.
2. From F. Ceriotti et al, IFCC Committee on Reference intervals and Detection Limits (C-RIDL) “Reference Intervals for Serum Creatinine: Assessment of data for Global Application” Clin. Chem. 54: 559-566, 2008
N. Proposed labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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