(90 days)
- VITROS Chemistry Products CRBM Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
- VITROS Chemistry Products CREA Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. 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.
- VITROS Chemistry Products TBIL Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block.
- VITROS XT 7600 Integrated System: Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended for use in the measurement of a variety of analytes of clinical interest.
The VITROS XT 7600 Integrated System is a fully automated, computer controlled, clinical chemistry and immunodiagnostic analyzer intended for the in vitro determination of a variety of general chemistries, therapeutic drugs, drugs of abuse, proteins, infectious diseases, as well as cardiac, metabolic, thyroid, anemia, and oncology markers in biological fluids such as serum, plasma, urine and cerebral spinal fluid. The System operates in conjunction with reagents, calibrators and controls designed for use with the System in the MicroSlide, MicroTip or MicroWell format.
The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, and VITROS Chemistry Products TBIL Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CRBM, CREA, and TBIL assays.
The document describes the performance of the VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, VITROS Chemistry Products TBIL Slides, and the VITROS XT 7600 Integrated System. The main purpose of the study is to demonstrate substantial equivalence to legally marketed predicate devices.
Here's an analysis of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state acceptance criteria in a dedicated table format for each performance metric, but rather describes how results were evaluated in the "Specificity" section and implies acceptance based on the comparison to predicate devices and established guidelines. For the method comparison, precision, linearity, and detection limits, the "reported device performance" is the direct result of the testing.
Given the nature of the submission (510(k) for substantial equivalence in an in-vitro diagnostic device), the acceptance criteria would typically revolve around demonstrating comparable performance to the predicate devices and adherence to established clinical laboratory standards (CLSI guidelines).
Below is a table summarizing the reported performance, with implied acceptance criteria based on standard practices for demonstrating substantial equivalence for in-vitro diagnostic devices.
Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Implied Acceptance Criteria (Based on Substantial Equivalence and CLSI Guidelines) | Reported Device Performance (VITROS XT 7600 Integrated System with corresponding slides) |
|---|---|---|
| Method Comparison | Device results should show substantial agreement with the predicate device (e.g., slopes near 1, intercepts near 0, demonstrating agreement across the measuring range). | CRBM Serum: N=118, Deming Regression, Slope=1.00, Intercept=0.12, Test range 3.1-17.8 µg/mL. CREA Serum: N=116, Passing Bablock, Slope=0.99, Intercept=0.00, Test range 0.25-13.4 mg/dL. CREA Urine: N=122, Passing Bablock, Slope=0.99, Intercept=-0.45, Test range 3.7-331.0 mg/dL. TBIL Serum: N=125, Passing Bablock, Slope=0.99, Intercept=0.01, Test range 0.14-23.65 mg/dL. |
| Precision | Within-lab precision (Total %CV and SD) should be acceptable for clinical use and comparable to predicate device specifications (though explicit predicate precision isn't stated here, it's an implied comparison). Lower %CV indicates higher precision. | CRBM (Serum): Within Lab (Total) %CV ranges from 2.41% to 3.98% across 6 concentration levels (3.9 to 17.6 µg/mL). |
| CREA (Serum): Within Lab (Total) %CV ranges from 1.40% to 1.85% across 6 concentration levels (0.82 to 12.65 mg/dL). | ||
| CREA (Urine): Within Lab (Total) %CV ranges from 1.55% to 2.23% across 6 concentration levels (55.6 to 320.9 mg/dL). | ||
| TBIL (Serum): Within Lab (Total) %CV ranges from 1.40% to 6.72% across 5 concentration levels (0.3 to 21.6 mg/dL). | ||
| Linearity | The device should demonstrate linearity across its claimed measuring range. | The linearity studies support the claimed measuring ranges for the VITROS CRBM, VITROS CREA, and VITROS TBIL assays. |
| Detection Limits (LoB, LoD, LoQ) | Calculated detection limits should be at or below the claimed LoQ and support the low end of the claimed measuring range. Acceptance typically involves comparing these values to the claimed LoQ. | CRBM: LoB = 0.6108 µg/mL; LoD = 0.6821 µg/mL; LoQ = 2.6860 µg/mL. Claimed LoQ = 3.0 µg/mL. TBIL: LoB = 0.0378 mg/dL; LoD = 0.0722 mg/dL; LoQ = 0.0616 mg/dL. Claimed LoQ = 0.10 mg/dL. Creatinine (Serum/Plasma): LoB = 0.0933 mg/dL; LoD = 0.0991 mg/dL; LoQ = 0.1119 mg/dL. Claimed LoQ = 0.15 mg/dL. Creatinine (Urine): LoB = 1.9973 mg/dL; LoD = 2.1986 mg/dL; LoQ = 2.0060 mg/dL. Claimed LoQ = 3.2 mg/dL. In all cases, the calculated LoQ is at or below the claimed LoQ, supporting the claimed assay range. |
| Specificity (Interference) | Observed bias due to interferents should be within predetermined Maximum Allowable Interference (MAI) or within the 95% Confidence Limit if exceeding Claimed Bias, demonstrating comparable performance to the predicate for known and potential interferents. | Results demonstrate acceptable bias on the VITROS XT 7600 versus the VITROS 5600 for currently claimed interferents. Two previously untested analyte/interferent levels (3.0 ug/mL CRBM/ 20 mg/dL Bilirubin and 3.0 ug/mL CRBM/ 3.0 mg/dL Ethamsylate on CRBM MicroSlides) yielded new information. One new interfering substance, Tolazamide, was identified for CREA(s) MicroSlides. The bias profiles for these demonstrated equivalent magnitudes to the VITROS 5600. The IFU for CRBM and CREA have been updated to claim the additional interfering levels and the new interfering substance. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Method Comparison Test Set:
- CRBM: 118 human serum samples.
- CREA: 116 human serum samples and 122 human urine samples.
- TBIL: 125 human serum samples.
- Data Provenance: The document states "human serum samples" and "human urine samples," implying these are clinical samples. The country of origin and whether the data is retrospective or prospective is not specified.
-
Precision Test Set: For each assay (CRBM, CREA serum, CREA urine, TBIL), the study involved:
- 80 replicates (N=80) for each of the multiple fluid levels (e.g., 6 for CRBM, 6 for CREA serum, 6 for CREA urine, 5 for TBIL). The total number of analyses is much higher (e.g., 80 replicates x 6 levels = 480 for CRBM).
- The samples used were Quality Control fluids and human-based precision fluids.
- Data Provenance: Not specified.
-
Linearity Test Set: A series of eleven proportionally related admixtures of low and high test fluids. Each sample was tested in triplicate.
- Data Provenance: Not specified.
-
Detection Limits (LoB, LoD, LoQ) Test Set:
- LoB: 4 blank samples, 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).
- LoD: 4 pools of human samples with analyte concentrations close to the expected detection limit, 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).
- LoQ: 4 pools of low level samples, 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).
- Data Provenance: The LoD and LoQ studies used "human samples." The country of origin and whether the data is retrospective or prospective is not specified.
-
Specificity (Interference) Test Set: Chemical interferents, common chemical substances, and claimed non-interferents, including hemoglobin, bilirubin, and intralipid. Testing employed "paired-difference" assessment at a minimum of two analyte levels.
- Data Provenance: Not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This device measures quantitative concentrations of specific analytes (Carbamazepine, Creatinine, Total Bilirubin). Ground truth for these types of in vitro diagnostic devices usually refers to the reference method (predicate device in this case) or a highly accurate reference standard rather than expert interpretation in the way it applies to image analysis or clinical diagnosis. The document does not mention human experts establishing ground truth in the context of radiologists or similar clinical diagnosticians. The ground truth for the method comparison study was established by the predicate device, VITROS 5600 Integrated System.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
None mentioned. Adjudication methods are typically used when there's a subjective element to ground truth establishment, often involving multiple human readers for diagnostic image interpretation. For quantitative measurements in clinical chemistry, the "truth" is established by reference methods, precision, and linearity studies, not by human adjudication of results.
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
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation, particularly in radiology or pathology, and often involves AI assistance. This document describes an automated in-vitro diagnostic device for quantitative chemical measurements, where human interpretation of results is direct measurement rather than subjective assessment. Therefore, the concept of "human readers improving with AI assistance" is not applicable here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are, in essence, standalone performance evaluations of the VITROS XT 7600 Integrated System itself, with the VITROS Chemistry Products slides, operating automatically without continuous human intervention during the measurement process. The system performs the tests, generates results, and its performance (method comparison, precision, linearity, detection limits, specificity) is evaluated. The comparison is against a predicate device, which is also an automated system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the test set, especially for the method comparison, was established by comparison to the legally marketed predicate device (VITROS 5600 Integrated System), which itself would have been previously cleared based on demonstrating accuracy against established reference methods or accepted gold standards for each analyte. For precision, linearity, and detection limits, the ground truth is established by the known characteristics of reference materials and statistical analysis.
8. The sample size for the training set
The document does not mention a training set. This is because the device described is not an AI/ML-based diagnostic algorithm that learns from data. It is a traditional in-vitro diagnostic instrument with chemical reagent slides. The studies are validation studies for the performance of the integrated system, not for training an algorithm.
9. How the ground truth for the training set was established
Since there is no training set mentioned or used for this type of device, this question is not applicable.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in a stacked format.
October 30, 2018
Ortho-Clinical Diagnostics, Inc. Marlene Hanna Director, Regulatory Affairs 100 Indigo Creek Drive Rochester, NY 14626
Re: K182063
Trade/Device Name: VITROS Chemistry Products CRBM Slides VITROS Chemistry Products CREA Slides VITROS Chemistry Products TBIL Slides VITROS XT 7600 Integrated System Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: JFY, KLT, CIG, JJE 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 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) K182063
Device Name VITROS Chemistry Products CRBM Slides VITROS Chemistry Products CREA Slides VITROS Chemistry Products TBIL Slides VITROS XT 7600 Integrated System
Indications for Use (Describe)
-
VITROS Chemistry Products CRBM Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
-
VITROS Chemistry Products CREA Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. 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.
-
VITROS Chemistry Products TBIL Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block.
-
VITROS XT 7600 Integrated System: Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended for use in the measurement of a variety of analytes of clinical interest.
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: K182063
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 CRBM Slides VITROS Chemistry Products CREA Slides VITROS Chemistry Products TBIL Slides VITROS XT 7600 Integrated System
Common Names:
Carbamazepine assay Creatinine assay Total bilirubin assay Clinical chemistry analyzer
Classification Names
| VITROS | Product Code | Class | Regulation Section | Panel |
|---|---|---|---|---|
| CRBM | KLT | Class II | 21 CFR 862.3645 Neuroleptic drugs radioreceptor assay test system. | Clinical Toxicology |
| CREA | JFY | Class II | 21 CFR 862.1225 creatinine test system | Clinical Chemistry |
| TBIL | CIG | Class II | 21 CFR 862.1110 Bilirubin (total or direct) test system. | Clinical Chemistry |
| XT 7600 | JJE | Class I | 21 CFR 862.2160 Discrete photometric chemistry analyzer for clinical use | Clinical Chemistry |
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Predicate Device(s)
| No. | New Devices | Predicate Devices | Predicate DeviceFDA 510(k)Number |
|---|---|---|---|
| 1 | VITROS ChemistryProducts CRBM Slides | VITROS ChemistryProducts CRBM Slides | K160495 |
| 2 | VITROS ChemistryProducts CREA Slides | VITROS ChemistryProducts CREA Slides | K063591 |
| 3 | VITROS ChemistryProducts TBIL Slides | VITROS ChemistryProducts TBIL Slides | K840880 |
| 4 | VITROS XT 7600Integrated System | VITROS 5600Integrated System | K081543 |
Intended Use Statement(s)
1. VITROS Chemistry Products CRBM Slides
Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
2. VITROS Chemistry Products CREA Slides
Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. 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.
3. VITROS Chemistry Products TBIL Slides
Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver, hemolytic hematological and metabolic disorders, including hepatitis and gall bladder block.
4. VITROS XT 7600 Integrated System
Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended for use in the measurement of a variety of analytes of clinical interest.
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Device Description
The VITROS XT 7600 Integrated System is a fully automated, computer controlled, clinical chemistry and immunodiagnostic analyzer intended for the in vitro determination of a variety of general chemistries, therapeutic drugs, drugs of abuse, proteins, infectious diseases, as well as cardiac, metabolic, thyroid, anemia, and oncology markers in biological fluids such as serum, plasma, urine and cerebral spinal fluid. The System operates in conjunction with reagents, calibrators and controls designed for use with the System in the MicroSlide, MicroTip or MicroWell format.
The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, and VITROS Chemistry Products TBIL Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CRBM, CREA, and TBIL assays.
Comparison to Predicate Devices
The following tables show similarities and differences between the new and predicate devices.
| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS CRBM Slides | Predicate DeviceVITROS CRBMSlidesK160495 |
| Intended Use | Rx Only. For in vitro diagnosticuse only. VITROS ChemistryProducts CRBM Slidesquantitatively measurecarbamazepine (CRBM)concentration in serum and plasma. | Same |
| Basic principle | Multiple-point Immunorate | Same |
| ReactiveIngredientsper cm2 | Immobilized mouse monoclonalanti-carbamazepine antibody0.02 mg; carbamazepine-horseradish peroxidase conjugate1.6 ng; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl) imidazole(leuco dye) 0.02 mg. | Same |
| Wavelength | 670 nm, 540 nm is also used for washdetection | Same |
| Sample type | Serum and plasma | Same |
| Sample volume | 11 μL | Same |
Table 1 VITROS Chemistry Products CRBM Slides
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| Differences | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS CRBM Slides | Predicate DeviceVITROS CRBMSlidesK160495 |
| 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 CREA Slides
| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS CREA Slides | Predicate DeviceVITROS CREA SlidesK063591 |
| Intended Use | Rx Only. For in vitro diagnosticuse only. VITROS ChemistryProduct CREA Slidesquantitatively measure creatinine(CREA) concentration in serum,plasma, and urine. | Same |
| Basic principle | Two-point rate | Same |
| ReactiveIngredientsper cm2 | Creatinine amidohydrolase(Flavobacterium sp.) 0.20 U; creatineamidinohydrolase (Alcaligenes sp.) 3.6U; sarcosine oxidase (Bacillus sp.)0.55 U; peroxidase (horseradish root)1.6 U and 2- (3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl) imidazole(leuco dye) 32 μg. | Same |
| Wavelength | 670 nm | Same |
| Sample type | Serum, plasma, urine | Same |
| Sample volume | 6 μL | Same |
| Differences | ||
|---|---|---|
| DeviceCharacteristic | Candidate | Predicate Device |
| VITROS CREA Slides | VITROS CREA Slides | |
| K063591 |
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| 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 3 VITROS Chemistry Products TBIL Slides
| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS TBIL Slides | Predicate DeviceVITROS TBILSlidesK840880 |
| Intended Use | Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma. | Same |
| Basic principle | Dual wavelength endpoint | Same |
| ReactiveIngredientsper cm2 | Dyphylline 0.5 mg and 4-(N-carboxymethylaminosulfonyl) benzene diazonium hexafluorophosphate 57 µg. | Same |
| Wavelength | measured at 2 wavelengths, 460 and 540nm | Same |
| Sample type | Serum and plasma | Same |
| Sample volume | 10 µL | Same |
| DeviceCharacteristic | CandidateVITROS TBIL Slides | Predicate DeviceVITROS TBILSlides K840880 |
|---|---|---|
| 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 |
Table 4 VITROS XT 7600 Integrated System
| Similarities | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS XT 7600 System | Predicate DeviceVITROS 5600System |
| K081543 | ||
| Similarities | ||
| DeviceCharacteristic | CandidateVITROS XT 7600 System | Predicate DeviceVITROS 5600SystemK081543 |
| System Features | ||
| Intended use | For use in the in vitro quantitative, semi-quantitative, and qualitativemeasurement of a variety of analytes ofclinical interest, using VITROSChemistry Products Slides, VITROSChemistry Products MicroTip Reagentsand VITROS ImmunodiagnosticProducts Reagents. | No change |
| Fundamentalscientifictechnology | MicroSlides - Colorimetric,Potentiometric, enzymatic endpoint andImmunorate assays.MicroTip and MicroWell reagentsThe analyzer uses four main detectionsystems:1) Reflection densitometry forcolorimetric and ImmunorateVITROS MicroSlides.2) Transmission spectrophotometryfor VITROS MicroTip assays.3) Enhanced chemiluminescentdetection for VITROS MicroWellassays.4) Electrometer for VITROSMicroSlide ion-selective electrode(ISE) assays. | No change |
| Operatingprinciple | Sample programming, samplingprocessing, result calculation, resultreporting | No change |
| Modes ofoperation | Continuous, Random, STAT | No change |
| Throughput | 845 tests per hour | No change |
| User interface | Touch screen (17 inch monitor),keyboard, ADD | No change |
| Sample andreagent volumeverification | Verification to ensure sufficient quantityof sample and reagent to run requestedassays | No change |
| On-BoardDilution Range | Dilution factor of 1: 400 | No change |
| Predictive alertsthrougheConnectivity | The predictive alerts are logged and areelectronically sent to the equipmentservice group real time for monitoring. | No change |
| Similarities | ||
| DeviceCharacteristic | CandidateVITROS XT 7600 System | Predicate DeviceVITROS 5600SystemK081543 |
| (remote access)Lab InformationSystem (LIS) | Enabled | No change |
| VAS LabAutomationSystem (LAS) | Enabled | No change |
| Specimen Sampling and Handling | ||
| Specimen type | Serum, Plasma, Urine, CSF, WholeBlood | No change |
| Specimencontainers | Cups, Primary Sample Collection Tubes | No change |
| Identification | Manual entry or Bar Code | No change |
| Specimenhandling | Universal Sample Tray | No change |
| Specimenprocessing | Auto-dilution, repeat and reflexcapabilities | No change |
| Automationcapabilities:10.25 mm tubefor pediatricsamples | Supported | No change |
| Sample QualityMonitoring(hemolysis,icterus andturbidity) | Yes | No change |
| Calibration | ||
| Calibrators | MicroSlide and MicroTip: analytespecific and multiple analytesMicroWell: analyte specific | No change |
| Identification | MicroSlide and MicroWell: Bar Code ormanual entryMicroTip: Manual entry | No change |
| CalibrationProgrammingFrequency | Sample tray can contain Calibrators, QCsamples and/or patient samplesAccording to the assay Instructions forUse | No change |
| CalibrationCompletionTimeMonitoring | Tracking time until calibrationcompletion is displayed to the operator. | No change |
| Similarities | ||
| DeviceCharacteristic | CandidateVITROS XT 7600 System | Predicate DeviceVITROS 5600SystemK081543 |
| Controls | MicroSlide and MicroTip: analyte specific and multiple analyteperformance verifiersMicroWell: analyte specific and multiple analyte selling controls andrange verifiers | No change |
| Review Mode | Review Data by Assay and by Event(scroll through multiple assays' QCresults which were run at the same time) | No change |
| Identification | Manual entry or Bar Code | No change |
| Frequency | According to the assay Instructions forUse. User configurable QC expirationinterval. | No change |
| QCProgramming | Programmed by assay | No change |
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| Differences | ||
|---|---|---|
| DeviceCharacteristic | CandidateVITROS XT 7600 System | Predicate DeviceVITROS 5600SystemK081543 |
| The followingsubsystems ofthe VITROS5600 IntegratedSystem will bemodified | REFL – ReflectometerSLIN – Slide IncubatorSLSU – Slide SupplySAIN – Sample IntegritySRME – Sample and Reagent MeteringSWCT – System Control and SampleProcessing SoftwareSWIN – Software InfrastructureSWUI – Graphical User InterfaceSoftwareADDI – Assay Data Disk. | All modificationspertain solely to theMicroSlideprocessing center.There are no changesbeing made to theMicroTip andMicroWellprocessing centers. |
Method Comparison
Method Comparison testing was designed and conducted in accordance with CLSI EP09-A3, "Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition" (2013).
Method comparison studies were conducted by testing a minimum of 116 human serum samples with analyte concentrations across the analytical ranges of carbamazepine, creatinine and total bilirubin assays on the VITROS XT 7600 Integrated System and the VITROS 5600 Integrated System (predicate device). In addition, 125 human urine samples were tested for creatinine on the
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candidate and predicate test systems. The results of the regression analyses for each of the assays are summarized below:
| VITROSassay | N | RegressionAnalysis | Slope | Intercept | Test range | ClaimedMeasuringRange |
|---|---|---|---|---|---|---|
| CRBMSerum(ug/mL) | 118 | Deming | 1.00 | 0.12 | 3.1-17.8 | 3.0-20.0 |
| CREASerum(mg/dL) | 116 | PassingBablock | 0.99 | 0.00 | 0.25-13.4 | 0.15-14.0 |
| CREAUrine(mg/dL) | 122 | PassingBablock | 0.99 | -0.45 | 3.7-331.0 | 3.2-346.5 |
| TBILSerum(mg/dL) | 125 | PassingBablok | 0.99 | 0.01 | 0.14-23.65 | 0.10-27.00 |
In addition to the above mentioned method comparison studies, testing was performed to determine the precision, linearity, LoB, LoD, LoQ, 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 Carbamazepine (CRBM), Creatinine (CREA), and Total Bilirubin (TBIL) assays.
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).
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| FluidID | Mean(ug/mL) | N | Repeatability(Within Run) | Within Day | Between Day | Between Cal | Within Lab(Total) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD(ug/mL) | %CV | SD(ug/mL) | %CV | SD(ug/mL) | %CV | SD(ug/mL) | %CV | SD(ug/mL) | %CV | |||
| CRBM-PP1 | 3.9 | 80 | 0.13 | 3.30 | 0.13 | 3.30 | 0.08 | 2.08 | 0.03 | 0.77 | 0.16 | 3.98 |
| CRBM-6155-1 | 4.7 | 80 | 0.14 | 2.97 | 0.14 | 3.02 | 0.00 | 0.00 | 0.07 | 1.40 | 0.16 | 3.32 |
| CRBM-6156-2 | 10.1 | 80 | 0.24 | 2.38 | 0.25 | 2.46 | 0.00 | 0.00 | 0.13 | 1.25 | 0.28 | 2.76 |
| CRBM-PP3 | 11.6 | 80 | 0.30 | 2.57 | 0.35 | 2.98 | 0.00 | 0.00 | 0.18 | 1.56 | 0.39 | 3.37 |
| CRBM-5896-3 | 13.1 | 80 | 0.29 | 2.19 | 0.35 | 2.67 | 0.00 | 0.00 | 0.22 | 1.64 | 0.41 | 3.14 |
| CRBM-PP5 | 17.6 | 80 | 0.33 | 1.86 | 0.37 | 2.10 | 0.10 | 0.57 | 0.18 | 1.03 | 0.42 | 2.41 |
CRBM Precision Table (Conventional units)
CREA Serum Precision Table (Conventional units)
| Repeatability(Within Run) | Within Day | Between Day | Between Cal | Within Lab(Total) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid ID | Mean(mg/dL) | N | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV |
| CREAS-5903-1 | 0.82 | 80 | 0.006 | 0.713 | 0.009 | 1.050 | 0.003 | 0.364 | 0.009 | 1.121 | 0.013 | 1.579 |
| CREAS-PP1 | 0.88 | 80 | 0.006 | 0.642 | 0.007 | 0.743 | 0.008 | 0.954 | 0.012 | 1.400 | 0.016 | 1.850 |
| CREAS-SRM | 0.99 | 80 | 0.007 | 0.697 | 0.008 | 0.829 | 0.006 | 0.568 | 0.014 | 1.396 | 0.017 | 1.720 |
| CREAS-5905-2 | 5.39 | 80 | 0.039 | 0.716 | 0.049 | 0.914 | 0.058 | 1.075 | 0.043 | 0.804 | 0.088 | 1.624 |
| CREAS-PP2 | 9.63 | 80 | 0.057 | 0.594 | 0.070 | 0.729 | 0.049 | 0.513 | 0.104 | 1.079 | 0.135 | 1.400 |
| CREAS-PP5 | 12.65 | 80 | 0.109 | 0.865 | 0.109 | 0.865 | 0.071 | 0.563 | 0.108 | 0.850 | 0.169 | 1.337 |
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| Fluid ID | Mean(mg/dL) | N | Repeatability(Within Run) | Within Day | Between Day | Between Cal | Within Lab(Total) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | |||
| CREAU-66791-1 | 55.6 | 80 | 0.58 | 1.05 | 0.67 | 1.20 | 0.43 | 0.77 | 0.96 | 1.72 | 1.24 | 2.23 |
| CREAU-PP1 | 78.4 | 80 | 1.10 | 1.40 | 1.13 | 1.44 | 0.35 | 0.45 | 0.68 | 0.86 | 1.36 | 1.73 |
| CREAU-URN | 88.0 | 80 | 0.69 | 0.79 | 0.98 | 1.11 | 0.29 | 0.33 | 0.97 | 1.10 | 1.41 | 1.60 |
| CREAU-66792-2 | 131.2 | 80 | 1.67 | 1.27 | 1.89 | 1.44 | 0.76 | 0.58 | 1.78 | 1.36 | 2.71 | 2.06 |
| CREAU-PP4 | 251.8 | 80 | 1.99 | 0.79 | 2.12 | 0.84 | 1.01 | 0.40 | 3.11 | 1.24 | 3.90 | 1.55 |
| CREAU-PP5 | 320.9 | 80 | 2.99 | 0.93 | 3.49 | 1.09 | 1.49 | 0.46 | 3.99 | 1.24 | 5.51 | 1.72 |
CREA Urine Precision Table (Conventional units)
TBIL Precision Table (Conventional units)
| Repeatability(Within Run) | Within Day | Between Day | Between Cal | Within Lab(Total) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fluid ID | Mean(mg/dL) | N | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV | SD(mg/dL) | %CV |
| TBIL-PP1 | 0.3 | 80 | 0.01 | 4.54 | 0.02 | 5.20 | 0.01 | 4.25 | 0.00 | 0.00 | 0.02 | 6.72 |
| TBIL-5903-1 | 1.6 | 80 | 0.03 | 1.68 | 0.04 | 2.88 | 0.01 | 0.51 | 0.03 | 1.84 | 0.05 | 3.45 |
| TBIL-PP3 | 6.5 | 80 | 0.03 | 0.52 | 0.06 | 0.87 | 0.06 | 0.88 | 0.04 | 0.64 | 0.09 | 1.40 |
| TBIL-5905-2 | 15.3 | 80 | 0.10 | 0.67 | 0.16 | 1.05 | 0.10 | 0.68 | 0.15 | 0.99 | 0.24 | 1.60 |
| TBIL-PP5 | 21.6 | 80 | 0.17 | 0.77 | 0.20 | 0.92 | 0.28 | 1.29 | 0.00 | 0.00 | 0.34 | 1.58 |
Linearity
Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline (2003). VITROS CRBM Slides, VITROS CREA Slides, and VITROS TBIL 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 CRBM, VITROS CREA, and VITROS TBIL assays.
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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 assay is 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 < 19% for carbamazepine; imprecision of ≤20% and percent total allowable error < 30% for creatinine in serum and urine, and imprecision of ≤25% and total allowable error < 0.09 mg/dL for total bilirubin in serum.
| CARB(µg/mL) | TBILmg/dL | Creatinine (mg/dL) | ||
|---|---|---|---|---|
| Serum/plasma | Urine | |||
| LoB | 0.6108 | 0.0378 | 0.0933 | 1.9973 |
| LoD | 0.6821 | 0.0722 | 0.0991 | 2.1986 |
| LoQ | 2.6860 | 0.0616 | 0.1119 | 2.0060 |
| Claimed LoQ | 3.0 | 0.10 | 0.15 | 3.2 |
| Assay Range | 3.0-20.0 | 0.10-27.00 | 0.15-14.0 | 3.2-346.5 |
The results of the detection capability studies for each assay are presented in the table below.
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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 CRBM, VITROS CREA and VITROS TBIL 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. 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.
- 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 levels vielded new information for currently claimed interferent compounds as a result of testing:
- 3.0 ug/mL CRBM/ 20 mg/dL Bilirubin on CRBM MicroSlides .
- . 3.0 ug/mL CRBM/ 3.0 mg/dL Ethamsylate on CRBM MicroSlides
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- 3.0 ug/mL CRBM/ 394 mg/dL Ethanol on CRBM MicroSlides ●
- 3.0 ug/mL CRBM/ 5.0 mg/dL Gentisic Acid on CRBM MicroSlides ●
- 3.0 ug/mL CRBM/ 100 mg/dL N-Acetylcysteine on CRBM MicroSlides
One new interfering substance was identified as a result of testing:
- . Tolazamide on CREA(s) MicroSlides
For the above, bias profiles on the VITROS XT 7600 demonstrated equivalent magnitudes to those using the VITROS 5600, using the noted substances. The Instructions for Use (IFU) for the VITROS CRBM and CREA assays have been updated to claim the additional interfering levels.
Conclusion
The data presented in this pre-market notification demonstrate that the performance of the VITROS XT 7600 Integrated System and the VITROS Chemistry Products assays are substantially equivalent to the cleared predicate devices. The VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA slides, and VITROS Chemistry Product TBIL Slides analyzed on the VITROS XT 7600 Integrated System are substantially equivalent to the VITROS Chemistry Products CRBM Slides (K160495), VITROS Chemistry Products CREA Slides (K063591), and VITROS Chemistry Products TBIL Slides (K840880) analyzed on the VITROS 5600 Integrated System.
Equivalence to predicates was demonstrated using commercially available reagents along with human serum, plasma, and urine samples.
The data presented in the premarket notification provide a reasonable assurance that the VITROS XT 7600 Integrated System and the VITROS assays are safe and effective for the stated intended uses.
§ 862.1225 Creatinine test system.
(a)
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.(b)
Classification. Class II.