(90 days)
-
VITROS Chemistry Products CI- Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products Cl-Slides quantitatively measure chloride (Cl-) concentration in serum, plasma and urine using VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
-
VITROS Chemistry Products ECO2 Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products ECO2 Slides quantitatively measure total carbon dioxide (CO2) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Bicarbonate/ carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.
-
VITROS Chemistry Products GLU Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products GLU Slides quantitatively measure glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products Cl- Slides, VITROS Chemistry Products ECO2 Slides, and VITROS Chemistry Products GLU Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CI-, ECO2, and GLU assays.
The provided text describes the performance evaluation of VITROS Chemistry Products Cl- Slides, ECO2 Slides, and GLU Slides on the VITROS XT 7600 Integrated System, demonstrating their substantial equivalence to predicate devices.
Here's an analysis of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied by the successful outcomes of the various performance studies (method comparison, precision, linearity, detection limits, specificity). Explicit numerical acceptance criteria are not always stated for each test result in the summary, but rather the conclusion that performance was "acceptable" or "supported the claimed measuring ranges."
Summary of VITROS XT 7600 Method Comparison Regression Analysis Data
| VITROS assay | Regression Analysis Type | Slope | Intercept | Test Range (Candidate) | Claimed Measuring Range | Performance Conclusion (Implicit Acceptance) |
|---|---|---|---|---|---|---|
| CL- Serum (mmol/L) | Passing Bablok | 1.00 | -0.11 | 51.2-167.5 | 50.0-175.0 | Acceptable (close to 1 slope, 0 intercept) |
| CI- Urine (mmol/L) | Weighted Deming | 1.00 | -0.11 | 15-290 | 15-300 | Acceptable (close to 1 slope, 0 intercept) |
| ECO2 Serum (mmol/L) | Deming | 0.99 | 0.19 | 7.1-38.4 | 5.0-40.0 | Acceptable (close to 1 slope, 0 intercept) |
| GLU Serum (mg/dL) | Weighted Deming | 1.00 | 0.49 | 22.1-593.8 | 20.0-625.0 | Acceptable (close to 1 slope, 0 intercept) |
| GLU Urine (mg/dL) | Weighted Deming | 1.00 | 0.28 | 25.3-600.4 | 20.0-650.0 | Acceptable (close to 1 slope, 0 intercept) |
| GLU CSF (mg/dL) | Weighted Deming | 1.00 | 0.22 | 22.9-649.5 | 20.0-650.0 | Acceptable (close to 1 slope, 0 intercept) |
Precision (Representative samples shown for Cl- Serum and ECO2)
The precision tables present the mean, N, SD, and %CV for Repeatability (Within Run), Within Day, Between Day, Between Calibration, and Within Lab (Total) for various fluids. The acceptance criteria are implicitly that the reported %CV and SD values are within acceptable clinical laboratory standards for these analytes, though specific numeric targets are not explicitly stated in this summary.
Detection Limits
| LoB (Reported) | LoD (Reported) | LoQ (Reported) | Claimed LoQ | Assay Range | Performance Conclusion (Implicit Acceptance) | |
|---|---|---|---|---|---|---|
| Cl- Serum | 9.2202 | 9.9798 | 49 | 50 | 50.0-175.0 | Reported LoQ is close to or better than Claimed LoQ |
| Cl- Urine | 3.0965 | 4.0417 | 11 | 15 | 15-300 | Reported LoQ is close to or better than Claimed LoQ |
| ECO2 | 1.9944 | 2.3522 | 3.7 | 5.0 | 5.0-40.0 | Reported LoQ is close to or better than Claimed LoQ |
| GLU Serum | 4.5753 | 5.2670 | 13 | 20 | 20.0-625.0 | Reported LoQ is close to or better than Claimed LoQ |
| GLU Urine | 6.2966 | 6.7212 | 20 | 20 | 20.0-650.0 | Reported LoQ is equal to Claimed LoQ |
| GLU CSF | 4.0745 | 4.6992 | 19 | 20 | 20.0-650.0 | Reported LoQ is close to or better than Claimed LoQ |
The acceptance criterion for LoQ is explicitly mentioned: "Ortho defines LoQ as the lowest concentration with an imprecision of ≤20% and percent total allowable error < 8% for chloride (serum); imprecision of ≤5 % and percent total allowable error < 10% for chloride (urine), imprecision of ≤20% and percent total allowable error < 30% for carbon dioxide, and imprecision of _20% and total allowable error < 30% for glucose in serum, urine, and CSF." The table shows the reported LoQ values are either equal to or lower than the claimed LoQ, indicating compliance.
Specificity (Interference Testing)
- Known Interferents: Observed bias compared to predetermined Maximum Allowable Interference (MAI) or Claimed Bias. If observed bias was within MAI and/or less than Claimed Bias, performance was acceptable. If greater than Claimed Bias, compared to 95% Confidence Limit (one-sided); acceptable if Claimed Bias fell within 95% CL.
- Potential Interferents and Non-Interfering Substances: Observed bias compared to MAI. Acceptable if within MAI. If greater than MAI, compared to 95% Confidence Limit (two-sided); acceptable if Claimed Bias fell within 95% CL.
- Performance: Results demonstrated "acceptable bias" for existing claimed interferents and led to updates in the Instructions For Use (IFU) for newly identified interferents (110 mmol/L Cl- with 4 mg/dL 4-Aminosalicylate on Cl- MicroSlides, and Triglyceride on Cl- MicroSlides).
2. Sample Sizes used for the Test Set and Data Provenance
- Method Comparison:
- Test Set Size: Minimum of 125 human serum samples for chloride, carbon dioxide, and glucose. 125 human urine samples for chloride. 125 human urine samples and 125 human CSF samples for glucose.
- Data Provenance: "human serum samples," "human urine samples," "human CSF samples" - indicating human origin, but specific countries are not mentioned. The studies appear to be prospective for the purpose of device validation.
- Precision:
- Test Set Size: Minimum of two Quality Control fluids and three human-based precision fluids for chloride, carbon dioxide, and glucose assays. Each specimen was tested for 80 runs (20 days, 2 runs/day, 2 replicates/specimen).
- Data Provenance: "human based precision fluids."
- Linearity:
- Test Set Size: A series of eleven proportionally related admixtures of low and high test fluids. Each sample tested in triplicate (with a minimum of two replicates acceptable for analysis).
- Data Provenance: Test fluids (specific origin not detailed).
- Detection Limits (LoB, LoD, LoQ):
- LoB: 4 blank samples tested in replicates of 6 over 3 days, using 3 lots of reagents (4 samples per day). Total of 216 observations (72 results per reagent lot).
- LoD: 4 pools of human samples tested in replicates of 6 over 3 days, using 3 lots of reagents (4 human sample pools per day). Total of 216 observations (72 results per reagent lot).
- LoQ: 4 pools of low-level samples tested in replicates of 4 over 3 days, using 3 lots of reagents (4 samples per day). Total of 144 observations (48 results per reagent lot).
- Data Provenance: "blank samples" and "human samples."
- Specificity (Interference Testing):
- Test Set Size: Not explicitly stated as a single number, but involved testing with known chemical interferents, common chemical substances, and "paireddifference" assessment at a minimum of two analyte levels.
- Data Provenance: Not explicitly stated, but implies laboratory-prepared samples with interferents.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This document describes in-vitro diagnostic devices for quantitative measurements. The "ground truth" here is typically established by reference methods or predicate devices and certified reference materials, not by human expert consensus or pathology review in the same way an AI imaging device would.
The studies compared the new device (VITROS XT 7600 Integrated System) against a predicate device (VITROS 5600 Integrated System), which is considered the "ground truth" or reference for establishing substantial equivalence in this context. The qualifications of personnel operating these systems or interpreting the raw data are not specified in this summary.
4. Adjudication Method for the Test Set
Not applicable in the context of quantitative IVD assays where results are numerical and compared against reference methods or predicate devices, rather than human expert interpretations. The comparisons described are statistical (e.g., Passing Bablok, Deming regression).
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 document is for in-vitro diagnostic devices (chemistry analyzers) that produce quantitative readings, not interpretative imaging or diagnostic aids that involve human "readers" or "AI assistance" in the sense of a decision support system.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are standalone performance evaluations of the VITROS XT 7600 Integrated System with the new VITROS Chemistry Products Slides. The system generates quantitative results without human interpretative input beyond operating the device and reviewing the numerical output. The "algorithm" here refers to the underlying chemical reactions and detection methods of the device itself.
7. The Type of Ground Truth Used
The ground truth for these studies was primarily established by:
- Predicate Device Comparison: The VITROS 5600 Integrated System served as the reference for method comparison studies.
- Reference Materials/Controls: Precision studies used quality control fluids and human-based precision fluids. Linearity used low and high test fluids. Detection limits used blank samples, human samples, and low-level samples. These are assumed to have known or established values.
- Statistical Guidelines: Adherence to CLSI guidelines (e.g., EP05-A3, EP06-A, EP17-A2, EP07-A2) implies the use of accepted methodologies for establishing performance characteristics.
8. The Sample Size for the Training Set
Not explicitly mentioned in terms of a "training set" as this is a traditional IVD device, not an AI/machine learning algorithm requiring a separate training phase. The analytical validation studies described (method comparison, precision, linearity, detection limits, specificity) serve to characterize the device's performance across its operational range, similar to a "test set" for validating generalizability.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a discrete "training set" for an AI algorithm is not described. The ground truth for the validation studies was established by comparison to the predicate device and the use of characterized control materials and human samples as detailed in point 7.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 30, 2018
Ortho-Clinical Diagnostics, Inc. Marlene Hanna Director, Regulatory Affairs 100 Indigo Creek Drive Rochester, NY 14626
Re: K182072
Trade/Device Name: VITROS Chemistry Products Cl-Slides VITROS Chemistry Products ECO2 Slides VITROS Chemistry Products GLU Slides Regulation Number: 21 CFR 862.1170 Regulation Name: Chloride test system Regulatory Class: Class II Product Code: CGZ, KHS, CGA Dated: July 30, 2018 Received: August 1, 2018
Dear Marlene Hanna:
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.
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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) 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) K182072
Device Name VITROS Chemistry Products Cl- Slides VITROS Chemistry Products ECO2 Slides VITROS Chemistry Products GLU Slides
Indications for Use (Describe)
-
VITROS Chemistry Products CI- Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products Cl-Slides quantitatively measure chloride (Cl-) concentration in serum, plasma and urine using VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
-
VITROS Chemistry Products ECO2 Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products ECO2 Slides quantitatively measure total carbon dioxide (CO2) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Bicarbonate/ carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.
-
VITROS Chemistry Products GLU Slides: Rx Only. For in vitro diagnostic use only.
VITROS Chemistry Products GLU Slides quantitatively measure glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
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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5 510(k) Summary Information
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K182072
Submitter's Information
Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-4041 Fax: (585) 453-3368
Contact Person:
Marlene Hanna, RAC Director, Regulatory Affairs
Date of Preparation: July 30, 2018
Device Proprietary Name(s):
VITROS Chemistry Products Cl- Slides VITROS Chemistry Products ECO2 Slides VITROS Chemistry Products GLU Slides
Common Names:
Chloride assay Carbon dioxide assay Glucose assay
Classification Names
| VITROS | ProductCode | Class | Regulation Section | Panel |
|---|---|---|---|---|
| Cl- | CGZ | Class II | 21 CFR 862. 1170 chloride test system | |
| ECO2 | KHS | Class II | 21 CFR 862. 1160 carbon dioxide test system | Clinical |
| GLU | CGA | Class II | 21 CFR 862. 1345 glucose test system | Chemistry |
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Predicate Device(s)
| No. | New Devices | Predicate Devices | Predicate DeviceFDA 510(k)Number |
|---|---|---|---|
| 1 | VITROS ChemistryProducts Cl- Slides | VITROS ChemistryProducts Cl- Slides | K162020 |
| 2 | VITROS ChemistryProducts ECO2 Slides | VITROS ChemistryProducts ECO2 Slides | K120765 |
| 3 | VITROS ChemistryProducts GLU Slides | VITROS ChemistryProducts GLU Slides | K163433 |
Intended Use Statement(s)
1. VITROS Chemistry Products Cl- Slides
Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products Cl- Slides quantitatively measure chloride (Cl-) concentration in serum, plasma and urine using VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
2. VITROS Chemistry Products ECO2 Slides
Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products ECO2 Slides quantitatively measure total carbon dioxide (CO2) concentration in serum and plasma using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.
3. VITROS Chemistry Products GLU Slides
Rx Only. For in vitro diagnostic use only.
VITROS Chemistry Products GLU Slides quantitatively measure glucose (GLU) concentration in serum, plasma, urine, and cerebrospinal fluid using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated Systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
Device Description
The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products Cl- Slides, VITROS Chemistry Products ECO2 Slides, and VITROS Chemistry Products GLU
{5}------------------------------------------------
Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CI-, ECO2, and GLU assays.
Comparison to Predicate Devices
The following tables show similarities and differences between the new and predicate devices.
| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS Cl- Slides | Predicate DeviceVITROS Cl- SlidesK162020 |
| Intended Use | Rx Only. For in vitro diagnosticuse only. VITROS ChemistryProducts Cl- Slides quantitativelymeasure chloride (Cl-)concentration in serum, plasma andurine. | Same |
| MethodPrinciple | Potentiometric; Electrode (ISE),Direct (undiluted) | Same |
| ReactiveIngredientsper cm2 | Silver 0.4 mg and silver chloride0.2 mg | Same |
| Sample type | Serum and plasma, urine | Same |
| Sample volume | 10 µL | Same |
| MeasuringRange | Serum: 50.0 -175.0 mmo/LUrine: 15-300 mmol/L | Same |
| Differences | ||
| DeviceCharacteristic | CandidateVITROS Cl- Slides | Predicate DeviceVITROS Cl- SlidesK162020 |
| Instrumentation | VITROS 250/350/950/5,1 FS and4600 Chemistry Systems and theVITROS 5600/ XT 7600 IntegratedSystem | VITROS250/350/950/5,1 FS and4600 ChemistrySystems and theVITROS 5600/XT 7600 Integrated System |
VITROS Chemistry Products Cl- Slides Table 1
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| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS ECO2 Slides | Predicate DeviceVITROS ECO2 SlidesK120765 |
| Intended Use | Rx Only. For in vitro diagnosticuse only. VITROS ChemistryProducts ECO2 Slidesquantitatively measure total carbondioxide (CO2) concentration inserum and plasma. | Same |
| Basic principle | Enzymatic Endpoint | Same |
| ReactiveIngredientsper cm2 | Phosphoenolpyruvate carboxylase(bacteria) 0.20 U; malatedehydrogenase (porcine heart) 0.26U; phosphoenolpyruvate0.39 mg and nicotinamide adeninedinucleotide, reduced 0.44 mg | Same |
| Wavelength | 340 nm | Same |
| Sample type | Serum, plasma | Same |
| Sample volume | 6 µL | Same |
| MeasuringRange | 5-40 mmol/L | Same |
| Differences | ||
| DeviceCharacteristic | CandidateVITROS ECO2 Slides | Predicate DeviceVITROS ECO2 SlidesK120765 |
| Instrumentation | VITROS 250/350/950/5,1 FS and4600 Chemistry Systems and theVITROS 5600/ XT 7600 IntegratedSystem | VITROS250/350/950/5,1 FS and4600 ChemistrySystems and theVITROS 5600Integrated System |
Table 2 VITROS Chemistry Products ECO2 Slides
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| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS GLU Slides | Predicate DeviceVITROS GLUSlides(K163433) |
| Intended Use | Rx Only. For in vitro diagnostic useonly. VITROS Chemistry ProductsGLU Slides quantitatively measureglucose (GLU) concentration inserum, plasma, urine, andcerebrospinal fluid | Same |
| Basic principleReactiveIngredientsper cm² | Colorimetric | Same |
| Glucose oxidase ( Aspergillus sp. ) 0.77 U;peroxidase (horseradish root) 3.6 U;1,7-dihydroxynaphthalene (dyeprecursor) 67 µg and 4-aminoantipyrine hydrochloride (dyeprecursor) 0.11 mg. | Same | |
| Wavelength | 540 nm | Same |
| Sample type | Serum, plasma, urine, CSF | Same |
| Sample volume | 6 µL | Same |
| MeasuringRange | Serum: 20.0-625.0 mg/dLUrine and CSF: 20.0-650.0 mg/dL | Same |
| Differences | ||
| DeviceCharacteristic | CandidateVITROS GLU Slides | Predicate DeviceVITROS GLUSlides(K163433) |
| Instrumentation | VITROS 250/350/950/5,1 FS and4600 Chemistry Systems and theVITROS 5600/ XT 7600 IntegratedSystem | VITROS250/350/950/5,1 FSand 4600 ChemistrySystems and theVITROS 5600Integrated System |
VITROS Chemistry Products GLU Slides Table 3
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Method Comparison
Method comparison studies were conducted by testing a minimum of 125 human serum samples with analyte concentrations within the measuring ranges (MR) of chloride, carbon dioxide and glucose assays on the VITROS XT 7600 Integrated System and the VITROS 5600 Integrated System (predicate device).
In addition, 125human urine samples were tested for chloride and 125 human urine samples and 125 human CSF samples were tested for glucose on the candidate and predicate test systems. The results are summarized below:
| VITROSassay | #SampleSTested | # Samples< MR,>MR | N | RegressionAnalysis | Slope | Intercept | Testrange | ClaimedMeasuringRange |
|---|---|---|---|---|---|---|---|---|
| CL-Serum(mmol/L) | 125 | 0 | 125 | PassingBablok | 1.00 | -0.11 | 51.2-167.5 | 50.0-175.0 |
| CI-Urine(mmol/L) | 125 | 2 | 123 | WeightedDeming | 1.00 | -0.11 | 15-290 | 15-300 |
| ECO2Serum(mg/dL) | 125 | 1 | 124 | Deming | 0.99 | 0.19 | 7.1-38.4 | 5.0-40.0 |
| GLUserum(mg/dL) | 125 | 1 | 124 | WeightedDeming | 1.00 | 0.49 | 22.1-593.8 | 20.0-625.0 |
| GLUUrine(mg/dL) | 125 | 0 | 125 | WeightedDeming | 1.00 | 0.28 | 25.3-600.4 | 20.0-650.0 |
| GLUcsf(mg/dL) | 125 | 0 | 125 | WeightedDeming | 1.00 | 0.22 | 22.9-649.5 | 20.0-650.0 |
Summary of VITROS XT 7600 Method Comparison Regression Analysis Data
MR=measuring range
In addition to the above mentioned method comparison studies, testing was performed to determine the precision, linearity, limit of detection, and Interfering substances of the representative VITROS assays on the VITROS XT 7600 System.
Precision
Precision studies were conducted following EP05-A3, Evaluation of Quantitative Measurement Procedures, Approved Guidelines – Third Edition (2014). The study was performed by testing a minimum of two Quality control fluids and three human based precision fluids using the chloride (Cl-), carbon dioxide (ECO2), and glucose (GLU) assays.
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Samples were analyzed using one VITROS XT 7600 Integrated System over 20 days, with 2 runs per day and 2 replicates per specimen (n=80).
| System | Fluid ID | Mean | N | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Repeatability (Within Run) | Within Day | Between Day | Between Cal | Within Lab (Total) | |||||||||
| 7600 | CLS-5903-1 | 86 | 80 | 0.4 | 0.5 | 0.5 | 0.6 | 0.6 | 0.7 | 0.6 | 0.7 | 1.0 | 1.2 |
| 7600 | CLS-5905-2 | 108 | 80 | 0.4 | 0.4 | 0.6 | 0.5 | 0.7 | 0.7 | 0.7 | 0.6 | 1.2 | 1.1 |
| 7600 | CLS-PP1 | 66 | 80 | 0.3 | 0.4 | 0.4 | 0.5 | 0.2 | 0.3 | 0.5 | 0.7 | 0.6 | 0.9 |
| 7600 | CLS-PP4 | 127 | 80 | 0.4 | 0.4 | 0.6 | 0.4 | 0.4 | 0.3 | 1.2 | 0.9 | 1.4 | 1.1 |
| 7600 | CLS-PP5 | 160 | 80 | 0.6 | 0.4 | 0.6 | 0.4 | 0.4 | 0.2 | 1.6 | 1.0 | 1.8 | 1.1 |
| 7600 | CLS-SRM | 106 | 80 | 0.4 | 0.3 | 0.5 | 0.5 | 0.3 | 0.3 | 1.0 | 0.9 | 1.2 | 1.1 |
Cl- Serum (mmol/L) Precision Table
Cl- Urine (mmol/L) Precision Table
| System | Fluid ID | Mean | N | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Repeatability(Within Run) | WithinDay | BetweenDay | BetweenCal | Within Lab(Total) | |||||||||
| 7600 | CLU-66791-1 | 101 | 80 | 0.4 | 0.3 | 0.6 | 0.6 | 0.2 | 0.2 | 0.7 | 0.7 | 0.9 | 0.9 |
| 7600 | CLU-66792-2 | 189 | 80 | 0.5 | 0.3 | 0.9 | 0.5 | 0.4 | 0.2 | 2.1 | 1.1 | 2.3 | 1.2 |
| 7600 | CLU-PP1 | 22 | 80 | 0.3 | 1.3 | 0.5 | 2.2 | 0.2 | 1.0 | 0.2 | 0.9 | 0.6 | 2.6 |
| 7600 | CLU-PP3 | 151 | 80 | 0.4 | 0.3 | 0.5 | 0.4 | 0.5 | 0.3 | 0.6 | 0.4 | 0.9 | 0.6 |
| 7600 | CLU-PP5 | 249 | 80 | 0.7 | 0.3 | 1.0 | 0.4 | 1.2 | 0.5 | 3.6 | 1.4 | 3.9 | 1.6 |
| 7600 | CLU-URN | 67 | 80 | 0.3 | 0.4 | 0.3 | 0.5 | 0.2 | 0.4 | 0.5 | 0.7 | 0.6 | 0.9 |
ECO2 (mmol/L) Precision Table
| System | Fluid ID | Mean | N | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Repeatability (Within Run) | Within Day | Between Day | Between Cal | Within Lab (Total) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-5903-1 | 26 | 80 | 0.3 | 1.0 | 0.4 | 1.4 | 0.5 | 1.9 | 0.0 | 0.0 | 0.6 | 2.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-5905-2 | 16 | 80 | 0.3 | 21.7 | 0.4 | 2.5 | 0.1 | 0.6 | 0.3 | 1.8 | 0.5 | 3.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-PP1 | 8 | 80 | 0.3 | 3.2 | 0.4 | 4.5 | 0.1 | 1.5 | 0.4 | 5.6 | 0.6 | 7.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-PP3 | 17 | 80 | 0.3 | 1.5 | 0.3 | 2.0 | 0.1 | 0.6 | 0.2 | 1.4 | 0.4 | 2.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-PP5 | 33 | 80 | 0.3 | 0.8 | 0.4 | 1.3 | 0.4 | 1.2 | 0.3 | 0.8 | 0.6 | 1.9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 7600 | ECO2-SRM | 26 | 80 | 0.2 | 0.8 | 1.1 | 4.2 | 0.4 | 1.5 | 0.0 | 0.0 | 1.2 | 4.4 |
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GLU (mg/dL) Serum Precision Table
| System | Fluid ID | Mean | N | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Repeatability (Within Run) | |||||||||||||
| Within Day | |||||||||||||
| Between Day | |||||||||||||
| Between Cal | |||||||||||||
| Within Lab (Total) | |||||||||||||
| 7600 | GLUS32-5903-1 | 89 | 80 | 0.4 | 0.4 | 0.6 | 0.7 | 0.5 | 0.6 | 0.0 | 0.0 | 0.8 | 0.9 |
| 7600 | GLUS32-5905-2 | 282 | 80 | 1.1 | 0.4 | 1.4 | 0.5 | 1.9 | 0.7 | 1.0 | 0.4 | 2.6 | 0.9 |
| 7600 | GLUS32-PP1 | 27 | 80 | 0.2 | 0.7 | 0.3 | 1.2 | 0.3 | 1.1 | 0.2 | 0.9 | 0.5 | 1.8 |
| 7600 | GLUS32-PP3 | 116 | 80 | 0.5 | 0.4 | 0.6 | 0.5 | 0.5 | 0.4 | 0.2 | 0.2 | 0.8 | 0.7 |
| 7600 | GLUS32-PP5 | 566 | 80 | 1.7 | 0.3 | 2.5 | 0.4 | 2.4 | 0.4 | 5.0 | 0.9 | 6.1 | 1.1 |
| 7600 | GLUS32-SRM | 99 | 80 | 0.3 | 0.3 | 0.5 | 0.5 | 0.5 | 0.5 | 0.3 | 0.3 | 0.8 | 0.8 |
GLU (mg/dL) Urine Precision Table
| System | Fluid ID | Mean | N | Repeatability(Within Run) | WithinDay | BetweenDay | BetweenCal | Within Lab(Total) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||
| 7600 | GLU32-66791-1 | 29 | 80 | 0.2 | 0.6 | 0.4 | 1.3 | 0.3 | 1.2 | 0.4 | 1.4 | 0.7 | 2.2 |
| 7600 | GLU32-66792-2 | 285 | 80 | 1.4 | 0.5 | 2.3 | 0.8 | 0.9 | 0.3 | 0.8 | 0.3 | 2.6 | 0.9 |
| 7600 | GLU32-PP2 | 102 | 80 | 0.4 | 0.4 | 0.7 | 0.7 | 0.6 | 0.6 | 1.2 | 1.2 | 1.5 | 1.5 |
| 7600 | GLU32-PP3 | 232 | 80 | 1.1 | 0.5 | 2.4 | 1.0 | 3.5 | 1.5 | 0.9 | 0.4 | 4.3 | 1.9 |
| 7600 | GLU32-PP5 | 593 | 80 | 1.9 | 0.3 | 2.7 | 0.5 | 6.5 | 1.1 | 7.2 | 1.2 | 10.0 | 1.7 |
GLU (mg/dL) CSF Precision Table
| GLU (mg/dL) CSF Precision Table | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Repeatability(Within Run) | Within Day | BetweenDay | BetweenCal | Within Lab(Total) | |||||||||
| System | Fluid ID | Mean | N | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 7600 | GLUC32-5706-1 | 36 | 80 | 0.2 | 0.6 | 0.3 | 0.9 | 0.4 | 1.0 | 0.2 | 0.5 | 0.5 | 1.4 |
| 7600 | GLUC32-5707-2 | 84 | 80 | 0.4 | 0.5 | 0.5 | 0.6 | 0.3 | 0.4 | 0.2 | 0.2 | 0.6 | 0.8 |
| 7600 | GLUC32-CSF | 41 | 80 | 0.2 | 0.5 | 0.3 | 0.6 | 0.3 | 0.9 | 0.2 | 0.4 | 0.5 | 1.2 |
| 7600 | GLUC32-PP1 | 28 | 80 | 0.1 | 0.5 | 0.3 | 1.1 | 0.3 | 1.2 | 0.3 | 0.9 | 0.5 | 1.9 |
| 7600 | GLUC32-PP4 | 289 | 80 | 1.3 | 0.5 | 1.7 | 0.6 | 1.4 | 0.5 | 2.2 | 0.7 | 3.1 | 1.1 |
| 7600 | GLUC32-PP5 | 563 | 80 | 2.6 | 0.5 | 3.7 | 0.7 | 3.6 | 0.6 | 2.8 | 0.5 | 5.8 | 1.0 |
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Linearity
Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline (2003). VITROS CI- Slides, VITROS ECO2 Slides, and VITROS GLU Slides were tested on the VITROS XT 7600 Integrated System. A series of eleven proportionally related admixtures of low and high test fluids were tested to verify linearity; each sample was tested in triplicate, a minimum of two replicates was acceptable for analysis.
The linearity studies support the claimed measuring ranges for the VITROS CI-, VITROS ECO2, and VITROS GLU assays.
Detection Limits
Detection capability studies for each analyte were evaluated based upon CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurements Procedures: Approved Guidelines – Second Edition (2012).
Limit of blank (LoB) studies were performed by testing 4 blank samples. Samples were tested in replicates of 6 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 216 observations (72 results per reagent lot). The LoB value for each assay was defined as the highest value achieved using blank samples with the stated probability (i.e. α.= 5%). Since the data for all assays were non-gaussian, a non-parametric approach was applied that estimates the LoB using the calculated rank position corresponding to the 95th percentile of the distribution of blank values observed."
Limit of detection (LoD) studies were performed by testing 4 pools of human samples with analyte concentrations close to the expected detection limit for each analyte. Samples were tested in replicates of 6 over 3 days, using 3 lots of reagents, with the 4 human sample pools every day. for a total of 216 observations (72 results per reagent lot). The data were analyzed according to CLSI EP17-A2, using CLSI-approved statistical software Analyse-it version 4.95.4, Method Validation Edition (Analyse-it Software Limited, Leeds UK). The software calculated LoD using a pooled SD from the low level fluid results and the input LoB value for the assay. determined as described above. The LoD value for the highest resultant value achieved among the combinations of reagent lots and human pools evaluated, with the stated probability (i.e. ß= 5%).
Limit of Quantitation studies were performed using 4 pools of low level samples with analyte concentrations close to the expected LoQ of the corresponding assay. Samples were tested in replicates of 4 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 144 observations (48 results per reagent lot). Ortho defines LoQ as the lowest concentration with an imprecision of ≤20% and percent total allowable error < 8% for chloride (serum); imprecision of ≤5 % and percent total allowable error < 10% for chloride (urine), imprecision of ≤20% and percent total allowable error < 30% for carbon dioxide, and imprecision of __20% and total allowable error < 30% for glucose in serum, urine, and CSF.
{12}------------------------------------------------
| Cl- Serum(mmol/L) | Cl- Urine(mmol/L) | ECO2(mmol/L) | GLU (mg/dL) | |||
|---|---|---|---|---|---|---|
| Serum | Urine | CSF | ||||
| LoB | 9.2202 | 3.0965 | 1.9944 | 4.5753 | 6.2966 | 4.0745 |
| LoD | 9.9798 | 4.0417 | 2.3522 | 5.2670 | 6.7212 | 4.6992 |
| LoQ | 49 | 11 | 3.7 | 13 | 20 | 19 |
| Claimed LoQ | 50 | 15 | 5.0 | 20 | 20 | 20 |
| Assay Range | 50.0-175.0 | 15-300 | 5.0-40.0 | 20.0-625.0 | 20.0-650.0 | 20.0-650.0 |
The results of the detection capability studies for each assay are presented in the table below.
Specificity
Interference Testing was performed in accordance with CLSI EP07-A2. Interference Testing in Clinical Chemistry, Approved Guidance-Second Edition. Clinical and Laboratory Standards Institute. November 2005, using VITROS CI , VITROS ECO2 and VITROS GLU assays.
Assays were tested on one VITROS XT 7600 Integrated System ('VITROS XT 7600, Test System) and one VITROS 5600 Integrated System (VITROS 5600. Predicate/Control System). Testing on the representative assays included known chemical interferents, common chemical substances identified with potential to interfere based upon risk assessment, as well as several claimed non-interferents. If hemoglobin, bilirubin, and/or intralipid were not previously identified as known interferents for the representative assays, Hemolysis, Icterus and/or Turbidity (HIT) indices, respectively, were evaluated during testing employed "paireddifference" assessment at a minimum of two analyte levels, as specified by CLSI EP07-A2.
*VITROS Chemistry Products MicroSensor™: Sub-system of analyzer that performs automated semi-quantitative sample quality index determinations on serum/plasma and cerebrospinal fluid samples. The sample quality index determinations performed are hemolysis, icterus, and turbidity; also referred to as 'HIT indices' or 'sample integrity indices'.
Results were evaluated as follows:
Known Interferents: The observed bias was compared to predetermined acceptance criteria (the Maximum Allowable Interference (MAI)) per product design input, and the Claimed Bias derived from product claims.
- . If the observed bias was within the MAI criteria (either in a positive or negative direction) and/or less than the Claimed Bias, performance was acceptable.
- If the observed bias was greater than the Claimed Bias, the bias was compared to the 95% . Confidence Limit (one-sided) per CLSI EP07-A2. If the Claimed Bias fell within the 95% Confidence Limit, performance was acceptable.
Potential Interferents and Non-Interfering Substances: The observed bias was compared to the Maximum Allowable Interference (MAI).
- If the observed bias was within the MAI criteria (either in a positive or negative . direction), performance was acceptable.
{13}------------------------------------------------
-
If the observed bias was greater than the MAI the bias was compared to the 95% ● Confidence Limit (two-sided) per CLSI EP07-A2. If the Claimed Bias fell within the 95% Confidence Limit, performance was acceptable.
Results demonstrate acceptable bias on the VITROS XT 7600 versus the VITROS 5600 for currently claimed interferents. The following previously untested analyte/interferent level yielded new information for a currently claimed interferent compound as a result of testing: -
110 mmol/L Cl7 4 mg/dL 4-Aminosalicylate on C1 MicroSlides ●
One additional interfering substance was identified as a result of testing: -
Triglyceride on Cl¯(s) MicroSlides
For the interferent indicated, bias profiles on the VITROS XT 7600 demonstrated equivalent magnitudes to those using the VITROS 5600, using the noted substance. The Instructions for Use (IFU) for the VITROS CI assay has been updated to claim the additional interfering substances.
Conclusion
The conclusions drawn from the nonclinical tests (discussed above) demonstrate the VITROS Chemistry Products Cl- Slides, VITROS Chemistry Product CREA Slides, and VITROS Chemistry Product GLU Slides for use on the VITROS XT 7600 Integrated System are as safe, effective, and perform as well as the predicate devices. The information submitted in the premarket notification is complete and supports a substantial equivalence decision.
§ 862.1170 Chloride test system.
(a)
Identification. A chloride test system is a device intended to measure the level of chloride in plasma, serum, sweat, and urine. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.(b)
Classification. Class II.