(268 days)
The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a]] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
Tina-quant Lipoprotein (a) Gen.2 Molarity assay quantifies lipoprotein (a) in human serum and plasma and reports the values in nmoVL with calibrator values traceable to the WHO/IFCC SRM2B reference material.
Reagents - working solutions
R1: Glycine buffer: 170 mmol/L. pH 7.0: stabilizers: BSA: rabbit serum 0.1 %, preservative
R3: Latex particles coated with polyclonal anti-human lipoprotein (a) antibodies (rabbit): 0.5 %; glycine buffer: 170 mmol/L, pH 7.3, BSA; preservative
Here's a breakdown of the acceptance criteria and study details for the Tina-quant Lipoprotein (a) Gen.2 Molarity assay, based on the provided document:
This device is an in vitro diagnostic (IVD) assay, not an AI/ML-driven device. Therefore, the concepts of human readers, multi-reader multi-case (MRMC) studies, ground truth establishment by experts for images, training sets, and adjudication methods are not directly applicable in the typical sense as they would be for an AI model that interprets medical images. The "acceptance criteria" here refer to the predefined performance specifications for an analytical assay.
Device Name: Tina-quant Lipoprotein (a) Gen.2 Molarity
1. Table of Acceptance Criteria and Reported Device Performance
The document states, "All acceptance criteria were met" for the non-clinical performance evaluation sections (Precision, Analytical Sensitivity, Linearity, Dilution, High Dose Hook Effect, Endogenous Interferences, Analytical Specificity/Cross-Reactivity, Sample Matrix Comparison, Method Comparison, and Stability). Specific pre-defined acceptance criteria are generally internal to the manufacturer's quality system and not explicitly listed in this 510(k) summary (which focuses on summarizing the results against those criteria). However, the reported device performance is provided, which demonstrates that the device met the manufacturer's internal criteria.
| Performance Characteristic | Acceptance Criteria (Implied/General) | Reported Device Performance (as stated in document) |
|---|---|---|
| Precision (Repeatability) | Within pre-defined CV% limits | CV% between 0.4% and 2.1% (for various samples) |
| Precision (Intermediate Precision) | Within pre-defined CV% limits | CV% between 0.7% and 2.6% (for various samples) |
| Limit of Blank (LoB) | LoB should be ≤ 6 nmol/L | LoB = 6 nmol/L |
| Limit of Detection (LoD) | LoD should be ≤ 7 nmol/L | LoD = 7 nmol/L |
| Limit of Quantitation (LoQ) | LoQ should be ≤ 7 nmol/L | LoQ = 7 nmol/L |
| Linearity/Assay Reportable Range | Linear within 7 – 240 nmol/L | Confirmed for the measuring range of 7 – 240 nmol/L |
| Dilution | Accurate dilution of samples > measuring range (1:3 rerun function) | Confirmed, supporting 1:3 dilution for samples above measuring range |
| High Dose Hook Effect | No false results up to a high concentration | Confirmed no false result up to 450 nmol/L |
| Endogenous Interferences | No significant interference from tested substances (Icterus, Hemolysis, Lipemia, Rheumatoid factors) | All predefined acceptance criteria were met. Claims: Icterus up to I index 60, Hemolysis up to H index 1000, Lipemia up to L index 2000, Rheumatoid factors up to 1200 IU/mL. |
| Analytical Specificity / Cross-Reactivity | No significant cross-reactivity from tested substances (Plasminogen, Apolipoprotein B) | No significant cross-reactivity in tested concentration ranges (Plasminogen up to 150 mg/dL, Apolipoprotein B up to 200 mg/dL). |
| Exogenous Interferences | No significant interference from common drug panels | All predefined acceptance criteria were met for 15 listed drugs at specified concentrations. |
| Sample Matrix Comparison | Acceptable performance across serum and different plasma types | All predefined acceptance criteria were met (Slope, Intercept, Correlation Coefficient for comparison of serum vs. serum with gel, Li-Heparin, K2-EDTA, K3-EDTA plasma). |
| Method Comparison to Lp(a) ELISA reference method | Strong correlation with reference method | Sample size (n) = 126. Deming regression: y = 1.023x + 0.692 nmol/L, r = 0.992. Sample concentrations 8.70 - 234 nmol/L. |
| Stability | Supports manufacturer's claims | Stability data supports Roche Diagnostic's claims as reported in the package labeling. |
2. Sample Sizes and Data Provenance
- Precision (Repeatability): n = 84 (number of individual measurements per sample level).
- Precision (Intermediate Precision): 2 aliquots per run, 2 runs per day, 21 days.
- LoB: One analyte-free sample measured with three reagent lots, 6 runs, 10-fold determination per run, distributed over >3 days.
- LoD: 5 serum samples with low analyte concentrations measured with three reagent lots, 2-fold determination per run, 6 runs distributed over 5 days.
- LoQ: 5 serum samples measured with three reagent lots, 5 runs distributed over 5 days.
- Linearity: 1 run using 3 reagent lots and 5 replicates per sample. A dilution series prepared from human serum (sample High) and NaCl 0.9% (sample Blank) to obtain 16 levels.
- Method Comparison (to Lp(a) ELISA): n = 126 native human serum samples.
- Sample Matrix Comparison: ≥ 50 samples.
- Reference Range Study:
- Caucasian/White: n = 425
- African-American/Black: n = 111
- Asian: n = 128
- Hispanic/Latino (among Caucasian/White): n = 110
- Non-Hispanic/Non-Latino (among Caucasian/White): n = 311
- Data Provenance for Reference Range Study: Samples from apparently healthy adults in the United States, with equal representation of males and females. This suggests prospective collection for the purpose of establishing reference ranges. Other studies (e.g., method comparison, precision) would typically use laboratory samples which could be retrospective or specifically prepared for the study. The document does not specify "retrospective" or "prospective" for all tests, but the nature of these analytical performance studies often involves controlled, prepared, or collected samples without a specific patient encounter context. The "native human serum samples" for method comparison generally implies biological samples.
3. Number of Experts and Qualifications for Ground Truth
For this in vitro diagnostic device, "ground truth" is established by reference methods or validated analytical measurements, not by human expert interpretation in the way it would be for an AI image analysis tool.
- Not Applicable in the traditional sense for AI/ML image analysis. The "ground truth" for analytical performance tests like precision, linearity, or interference is an established analytical value or the characteristic of the sample itself (e.g., known concentration, presence/absence of interfering substance). For "method comparison," the ground truth is provided by the designated "Lp(a) ELISA reference method."
4. Adjudication Method for the Test Set
- Not Applicable in the traditional sense for AI/ML image analysis. Adjudication is usually performed by multiple human experts reviewing a case. For an IVD, the "adjudication" is inherent in the rigorous analytical protocols, statistical methods (e.g., CLSI guidelines), and the use of reference methods or certified reference materials for traceability.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
- Not Applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging system that would involve human readers interpreting cases.
6. Standalone (i.e. algorithm only without human-in-the loop performance) Performance
- Yes, implicitly. The performance studies (Precision, Analytical Sensitivity, Linearity, Interference, Method Comparison) evaluate the device (assay on the cobas c 503 analyzer) as a standalone system. There is no human intervention in the measurement or calculation of results once the sample is loaded. The device generates a quantitative value for Lp(a).
7. The Type of Ground Truth Used
- Reference Method/Analytical Standards:
- Precision, Sensitivity, Linearity, Interferences: Ground truth is based on known concentrations in control materials, spiked samples, or by using analyte-free samples, following standardized laboratory practices and CLSI guidelines (e.g., CLSI EP05-A3, EP17-A2, EP06-A-Ed2).
- Method Comparison: The "ground truth" or reference values were derived from the Lp(a) ELISA reference method.
- Traceability: The device's calibration values are traceable to the WHO/IFCC SRM2B reference material for nmol/L, indicating a standardized and accepted reference for accuracy.
8. The Sample Size for the Training Set
- Not applicable in the AI/ML sense. This is a traditional IVD assay, not an AI model that requires a "training set" to learn features. The assay is based on well-understood principles of immunoturbidimetry and does not involve machine learning training.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As there is no AI/ML training set, this question is not relevant to this device. The assay's "knowledge" is built into its chemical reagents, optical detection system, and pre-programmed algorithms for calculating concentration from turbidity measurements, based on established analytical principles and calibration to reference materials.
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January 24, 2025
Image /page/0/Picture/1 description: The image shows 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 consists of a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font size below that.
Roche Diagnostics Leslie Patterson Senior Regulatory Affairs Manager 9115 Hague Road Indianapolis, Indiana 46250
Re: K241220
Trade/Device Name: Tina-quant Lipoprotein(a) Gen.2 Molarity Regulation Number: 21 CFR 21 CFR 866.5600 Regulation Name: Low-density Lipoprotein Immunological Test System Regulatory Class: Class II Product Code: DFC Dated: December 18, 2024 Received: December 18, 2024
Dear Leslie Patterson:
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 (the 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 available 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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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatory
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assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
Submission Number (if known)
K241220 Device Name
Tina-quant Lipoprotein (a) Gen.2 Molarity
Indications for Use (Describe)
The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a]] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
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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Tina-quant Lipoprotein (a) Gen.2 Molarity K241220 - 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0457 |
| Contact | Leslie PattersonPhone: (317) 225-8563Email: leslie.patterson@roche.com |
| Date Prepared | January 24, 2025 |
| Proprietary Name | Tina-quant Lipoprotein (a) Gen.2 Molarity |
| Classification Name | Low-density lipoprotein immunological test system. |
| Product Codes,Regulation Numbers | DFC, 21 CFR 866.5600 |
| Predicate Device | Tina-quant Lipoprotein (a) Gen.2 (K122722) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126Roche Diagnostics GmbH Penzberg, Germany: 9610529Roche Diagnostics Indianapolis, IN United States: 1823260 |
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DEVICE DESCRIPTION 1.
The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
Tina-quant Lipoprotein (a) Gen.2 Molarity assay quantifies lipoprotein (a) in human serum and plasma and reports the values in nmoVL with calibrator values traceable to the WHO/IFCC SRM2B reference material.
Reagents - working solutions 1.1.
R1: Glycine buffer: 170 mmol/L. pH 7.0: stabilizers: BSA: rabbit serum 0.1 %, preservative
R3: Latex particles coated with polyclonal anti-human lipoprotein (a) antibodies (rabbit): 0.5 %; glycine buffer: 170 mmol/L, pH 7.3, BSA; preservative
2. INDICATIONS FOR USE
The Tina-quant Lipoprotein (a) Gen.2 Molarity assay is an in vitro test for the quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma on cobas c systems. The measurement of Lp(a) is useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk, when used in conjunction with clinical evaluation and other lipoprotein tests.
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TECHNOLOGICAL CHARACTERISTICS 3.
The following table compares the Tina-quant Lipoprotein (a) Gen.2 Molarity assay with the predicate device, Tina-quant Lipoprotein (a) Gen.2 (K122722).
| Candidate Device:Tina-quant Lipoprotein (a)Gen.2 Molarity | Predicate Device:Tina-quant Lipoprotein (a)Gen.2 (K122722) | |
|---|---|---|
| Intended Use /Indications forUse | The Tina-quant Lipoprotein (a) Gen.2Molarity assay is an in vitro test for thequantitative determination of lipoprotein (a)[Lp(a)] in human serum and plasma oncobas c systems. The measurement ofLp(a) is useful in evaluating lipidmetabolism disorders and assessingatherosclerotic cardiovascular disease risk,when used in conjunction with clinicalevaluation and other lipoprotein tests. | In vitro test for the quantitativedetermination of lipoprotein (a) in humanserum and plasma on Roche/Hitachicobas c systems. The measurement ofLp(a) is useful in evaluating lipidmetabolism disorders and assessingatherosclerotic cardiovascular disease inspecific populations, when used inconjunction with clinical evaluation andother lipoprotein tests. |
| Assay Method | Same | Particle enhanced immunoturbidimetricassay |
| InstrumentPlatform | Same | cobas c systems |
| SampleType/Matrix | Same | Human serum and Li-heparin, K2-EDTA,K3-EDTA plasma |
| Calibrator | Same | Preciset Lp(a) Gen.2 |
| Traceability/Standardization | This method has been standardizedagainst the IFCC reference materialSRM2B for nmol/L. | This method has been standardizedagainst an in-house reference material. |
| CalibrationMethod | Same | 6-point, spline |
| CalibrationInterval | Automatic full calibration- after reagent lot changeFull calibration- as required following quality controlprocedures | Full calibration- after reagent lot change- as required following quality controlprocedures |
| Controls | Same | PreciControl Lp(a) Gen.2 |
| Measuring Range | 7-240 nmol/L | 6.0-80 mg/dL |
| Lower Limits ofMeasurement | LoB (Limit of Blank): 6 nmol/LLoD (Limit of Detection): 7 nmol/LLoQ (Limit of Quantitation): 7 nmol/L | LoB (Limit of Blank): 3 mg/dLLoD (Limit of Detection): 4 mg/dLLoQ (Limit of Quantitation): 6 mg/dL |
| Candidate Device:Tina-quant Lipoprotein (a)Gen.2 Molarity | Predicate Device:Tina-quant Lipoprotein (a)Gen.2 (K122722) | |
| MethodComparison | Method comparison between the candidate method, Tina-quant Lipoprotein (a) Gen.2Molarity assay and the Lp(a) ELISA reference method:Sample size (n) = 126 | |
| Deming regression | ||
| $y = 1.023x + 0.692$ nmol/L$r = 0.992$ | ||
| The sample concentrations were between 8.70 and 234 nmol/L. |
Technical Characteristics Comparison Table between Tina-quant Lipoprotein Table 1: (a) Gen.2 Molarity and Tina-quant Lipoprotein (a) Gen.2
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4. NON-CLINICAL PERFORMANCE EVALUATION
Performance characteristics were evaluated with Tina-quant Lipoprotein (a) Gen.2 Molarity on the cobas c 503 analyzer and are briefly summarized below.
All acceptance criteria were met.
Precision 4.1.
4.1.1. Repeatability and Intermediate Precision
Precision was determined in accordance with the CLSI EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer. The results are summarized below. All acceptance criteria were met.
| Repeatability | |||
|---|---|---|---|
| Sample | Mean (nmol/L) | SD (nmol/L) | CV (%) |
| Lp(a) Control Level Low | 35.2 | 0.412 | 1.2 |
| Lp(a) Control Level High | 97.7 | 0.435 | 0.4 |
| Human Serum 1 | 19.7 | 0.414 | 2.1 |
| Human Serum 2 | 49.3 | 0.516 | 1.0 |
| Human Serum 3 | 80.5 | 0.434 | 0.5 |
| Human Serum 4 | 120 | 0.546 | 0.5 |
| Human Serum 5 | 203 | 0.794 | 0.4 |
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| Intermediate Precision | |||
|---|---|---|---|
| Sample | Mean (nmol/L) | SD (nmol/L) | CV (%) |
| Lp(a) Control Level Low | 35.1 | 0.562 | 1.6 |
| Lp(a) Control Level High | 99.0 | 1.14 | 1.2 |
| Human Serum 1 | 19.7 | 0.508 | 2.6 |
| Human Serum 2 | 49.3 | 0.676 | 1.4 |
| Human Serum 3 | 80.5 | 0.831 | 1.0 |
| Human Serum 4 | 119 | 1.14 | 1.0 |
| Human Serum 5 | 203 | 1.33 | 0.7 |
Analytical Sensitivity 4.2.
Limit of Blank (LoB) 4.2.1.
For determination of LoB, one analyte-free sample was measured with three reagent lots in 6 runs, each run with 10-fold determination, distributed over >3 days, on the cobas c 503 analyzer. The LoB was determined according to CLSI EP17-A2. The LoB claim in the labeling will be set to LoB = 6 nmol/L.
Limit of Detection (LoD) 4.2.2.
For determination of LoD, 5 serum samples with low analyte concentrations were measured each three reagent lots with 2-fold determination per run on one cobas c 503 analyzer. Six runs were distributed over 5 days. The LoD was determined according to CLSI EP17-A2. The LoD claim in the labeling will be set to LoD = 7 nmol/L
4.2.3. Limit of Quantitation (LoQ)
For determination of LoQ, 5 serum samples were measured with three reagent lots on one cobas c 503. Five runs were distributed over 5 days. The Limit of Quantitation (LoQ) was determined according to CLSI EP17-A2. The LoQ claim in the labeling will be set to 7 nmol/L.
4.3. Linearity/Assay Reportable Range
The linearity of the Tina-quant Lipoprotein (a) Gen.2 Molarity assay was assessed according to CLSI EP06-A-Ed2.
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Linearity of the Tina-quant Lipoprotein (a) Gen.2 Molarity assay was assessed on one cobas c 503 analyzer in 1 run using 3 reagent lots and 5 replicates per sample. A dilution series was prepared from human serum (sample High) and NaCl 0.9% (sample Blank). The dilution series spanning the measuring range were prepared to obtain 16 levels.
Linearity was confirmed for the measuring range of 7 – 240 nmol/L.
4.4. Dilution
Post Dilution Check experiments were performed for samples above the measuring range and verify dilution of samples via the rerun function is a 1:3 dilution. Samples with concentrations above the measuring range were measured with the Tina-quant Lipoprotein (a) Gen.2 Molarity assay on the cobas c 503 via the automatic rerun function. The target values were determined with the ELISA reference method.
High Dose Hook Effect 4.5.
High-dose hook effect study was performed using the Tina-quant Lipoprotein (a) Gen.2 Molarity assay and confirmed that no false result occurs up to a lipoprotein (a) concentration of 450 nmol/L.
Endogenous Interferences 4.6.
Endogenous substances were evaluated for potential interference with the Tina-quant Lipoprotein (a) Gen.2 Molarity assay on the cobas c 503. All predefined acceptance criteria were met.
| EndogenousSubstance | ClaimNo significant interference up to |
|---|---|
| Icterus | I index of 60 for conjugated and unconjugated bilirubin(approximate conjugated and unconjugated bilirubin concentration: 1026µmol/L or 60 mg/dL). |
| Hemolysis | H index of 1000(approximate hemoglobin concentration: 621 µmol/L or 1000 mg/dL). |
| Lipemia (Intralipid) | L index of 2000There is poor correlation between the L index (corresponds to turbidity) andtriglycerides concentration. |
| Rheumatoid factors | 1200 IU/mL |
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Analytical Specificity / Cross-Reactivity 4.7.
Plasminogen and Apolipoprotein B were evaluated for cross-reactivity and the labeling claims for each substance can be found below:
Plasminogen: No significant cross-reactivity in the tested concentration range (up to 150 mg/dL).
Apolipoprotein B: No significant cross-reactivity in the tested concentration range (up to 200 mg/dL).
4.8. Exogenous Interferences
Common drug panels were evaluated for potential interference with the Tina-quant Lipoprotein (a) Gen.2 Molarity assay on the cobas c 503 analyzer. All predefined acceptance criteria were met.
| Drug | Concentration Tested [mg/L] |
|---|---|
| N-Acetylcysteine | 150 |
| Acetylsalicylic acid | 30 |
| Ampicillin-Na | 75 |
| Ascorbic acid | 52.5 |
| Cefoxitin | 6600 |
| Doxycyclin | 18 |
| Heparin | 3300 IU/L |
| Levodopa | 7.5 |
| Methyldopa | 22.5 |
| Metronidazole | 123 |
| Rifampicin | 48 |
| Acetaminophen | 156 |
| Cyclosporine | 1.8 |
| Ibuprofen | 219 |
| Theophylline | 60 |
| Phenylbutazone | 321 |
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Sample Matrix Comparison 4.9.
The effect on quantitation of lipoprotein (a) values in the presence of anticoagulants with the Tina-quant Lipoprotein (a) Gen.2 Molarity assay was determined on the cobas c 503 analyzer by comparing values obtained from samples collected in serum, Li-Heparin, K2-EDTA and K3-EDTA plasma tubes. The study was performed using ≥ 50 samples measured on the cobas c 503 analyzer. All predefined acceptance criteria were met, supporting the labeling claim that serum, Li-Heparin, K2-EDTA and K3-EDTA plasma are acceptable sample types.
| Anticoagulant | Slope | Intercept(nmol/L) | Correlation Coefficient(Pearson r) | Concentration of Samples(nmol/L, serum) |
|---|---|---|---|---|
| Serum vs. Serum with gel separation | 1.000 | 0 | 1.000 | 7.51 - 239 |
| Serum vs. Li-Heparin plasma | 0.981 | 0.286 | 0.998 | 7.51 - 239 |
| Serum vs. K2-EDTA plasma | 0.972 | 0.134 | 1.000 | 7.51 - 233 |
| Serum vs. K3-EDTA plasma | 0.944 | 0.389 | 1.000 | 7.51 - 233 |
4.10. Method Comparison to Lp(a) ELISA reference method
A method comparison of the Tina-quant Lipoprotein (a) Gen.2 Molarity assay on the cobas c 503 analyzer compared to the Lp(a) ELISA reference method was completed. One hundred twenty-six native human serum samples were tested in singlicate using the cobas c 503 analyzer. The sample concentrations were between 8.70 and 234 nmoVL. The results can be found below:
Deming regression
y = 1.023x + 0.692 nmol/L
r = 0.992
4.11. Stability
The stability data supports Roche Diagnostic's claims as reported in the package labeling.
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CLINICAL PERFORMANCE EVALUATION 5.
Reference Range Study 5.1.
Roche conducted a reference range study and measured Lp(a) levels among various subpopulations. The expected ranges were determined using samples from apparently healthy adults in the United States, with an equal representation of males and females.
Lp(a) by Race
| n | Median | 2.5th percentile(90 %-CI) | 97.5th percentile(90 %-CI) | Unit | |
|---|---|---|---|---|---|
| Caucasian/White | 425 | 17.8 | < 7 (n.a.) | 259 (229; 265) | nmol/L |
| African-American/Black | 111 | 66.2 | < 7 (n.a.) | 267 (207; 313) | nmol/L |
| Asian | 128 | 19.9 | < 7 (n.a.) | 210 (166; 330) | nmol/L |
Lp(a) by Ethnicity (among Caucasian/White)
| n | Median | 2.5th percentile(90 %-CI) | 97.5th percentile(90 %-CI) | Unit | |
|---|---|---|---|---|---|
| Hispanic/Latino | 110 | 14.5 | < 7 (n.a.) | 260 (162; 267) | nmol/L |
| Non-Hispanic/Non-Latino | 311 | 18.1 | < 7 (n.a.) | 259 (229; 287) | nmol/L |
CLINICAL LITERATURE 6.
Associations between Lp(a) and ASCVD risk were demonstrated in multiple published clinical studies in and outside of the US, including the Dallas Heart Study and the UK Biobank Study (PMID: 27831500, PMID: 33115266). The UK Biobank Study was also used to derive Lp(a) thresholds for ASCVD risk (PMID: 36036785, PMID: 38565461). Information was provided to bridge the results from the published studies to the candidate device.
CONCLUSIONS 7.
The analytical performance data for Tina-quant Lipoprotein (a) Gen.2 Molarity assay met the acceptance criteria. The analytical performance data and clinical performance evaluation support the substantial equivalence of Tina-quant Lipoprotein (a) Gen.2 Molarity assay on the cobas c 503 analyzer to the predicate.
§ 866.5600 Low-density lipoprotein immunological test system.
(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).