(268 days)
No
The summary describes a standard in vitro diagnostic assay based on chemical reactions and quantitative measurements, with no mention of AI or ML.
No
This device is an in vitro diagnostic test for measuring lipoprotein (a) levels, which aids in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk. It does not provide treatment or directly alleviate a condition.
Yes
This device is an in vitro diagnostic (IVD) test ("in vitro test") designed for the "quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma." The measurement of Lp(a) is stated to be "useful in evaluating lipid metabolism disorders and assessing atherosclerotic cardiovascular disease risk," which directly indicates its use for diagnostic purposes.
No
The device is an in vitro diagnostic assay that includes chemical reagents (R1 and R3) for the quantitative determination of lipoprotein (a) in human serum and plasma. It is designed to be used on cobas c systems, which are hardware analyzers. Therefore, it is not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The description explicitly states it is an "in vitro test for the quantitative determination of lipoprotein (a) [Lp(a]] in human serum and plasma". This clearly indicates it is used to examine specimens derived from the human body outside of the body.
- Device Description: The description reiterates that it is an "in vitro test" and details the reagents used, which are components of an in vitro assay.
- Performance Studies: The document describes various performance evaluations typical for IVDs, such as precision, sensitivity, linearity, interference studies, and method comparison. These studies are conducted to demonstrate the analytical performance of the test.
The information provided aligns with the definition of an In Vitro Diagnostic device, which is used to examine specimens from the human body to provide information for diagnosis, monitoring, or screening.
N/A
Intended Use / 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.
Product codes
DFC
Device Description
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
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Non-clinical performance evaluations were conducted, including:
Precision: Repeatability and Intermediate Precision were determined in accordance with CLSI EP05-A3 requirements, with results summarized in tables. All acceptance criteria were met.
Analytical Sensitivity: Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) were determined according to CLSI EP17-A2. LoB = 6 nmol/L, LoD = 7 nmol/L, LoQ = 7 nmol/L.
Linearity/Assay Reportable Range: Assessed according to CLSI EP06-A-Ed2 on one cobas c 503 analyzer using 3 reagent lots and 5 replicates per sample. Linearity was confirmed for the measuring range of 7 – 240 nmol/L.
Dilution: Post Dilution Check experiments performed for samples above the measuring range, verifying 1:3 dilution via rerun function.
High Dose Hook Effect: No false result occurs up to a lipoprotein (a) concentration of 450 nmol/L.
Endogenous Interferences: Evaluated on cobas c 503; all predefined acceptance criteria met for Icterus, Hemolysis, Lipemia (Intralipid), and Rheumatoid factors.
Analytical Specificity / Cross-Reactivity: Plasminogen and Apolipoprotein B evaluated, showing no significant cross-reactivity.
Exogenous Interferences: Common drug panels evaluated; all predefined acceptance criteria met.
Sample Matrix Comparison: Effect of anticoagulants evaluated using ≥ 50 samples in serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma tubes on cobas c 503. All acceptance criteria met, supporting specified sample types.
Method Comparison to Lp(a) ELISA reference method: One hundred twenty-six native human serum samples tested in singlicate on the cobas c 503 analyzer compared to Lp(a) ELISA reference method. Sample concentrations between 8.70 and 234 nmol/L. Deming regression: y = 1.023x + 0.692 nmol/L, r = 0.992.
Stability: Data supports Roche Diagnostic's claims in package labeling.
Clinical performance evaluation:
Reference Range Study: Roche conducted a study to measure Lp(a) levels among various subpopulations using samples from apparently healthy adults in the United States, with equal representation of males and females. Expected ranges determined by race (Caucasian/White, African-American/Black, Asian) and ethnicity (Hispanic/Latino, Non-Hispanic/Non-Latino among Caucasian/White).
Key Metrics
Repeatability:
Lp(a) Control Level Low: Mean 35.2 nmol/L, SD 0.412 nmol/L, CV 1.2 %
Lp(a) Control Level High: Mean 97.7 nmol/L, SD 0.435 nmol/L, CV 0.4 %
Human Serum 1: Mean 19.7 nmol/L, SD 0.414 nmol/L, CV 2.1 %
Human Serum 2: Mean 49.3 nmol/L, SD 0.516 nmol/L, CV 1.0 %
Human Serum 3: Mean 80.5 nmol/L, SD 0.434 nmol/L, CV 0.5 %
Human Serum 4: Mean 120 nmol/L, SD 0.546 nmol/L, CV 0.5 %
Human Serum 5: Mean 203 nmol/L, SD 0.794 nmol/L, CV 0.4 %
Intermediate Precision:
Lp(a) Control Level Low: Mean 35.1 nmol/L, SD 0.562 nmol/L, CV 1.6 %
Lp(a) Control Level High: Mean 99.0 nmol/L, SD 1.14 nmol/L, CV 1.2 %
Human Serum 1: Mean 19.7 nmol/L, SD 0.508 nmol/L, CV 2.6 %
Human Serum 2: Mean 49.3 nmol/L, SD 0.676 nmol/L, CV 1.4 %
Human Serum 3: Mean 80.5 nmol/L, SD 0.831 nmol/L, CV 1.0 %
Human Serum 4: Mean 119 nmol/L, SD 1.14 nmol/L, CV 1.0 %
Human Serum 5: Mean 203 nmol/L, SD 1.33 nmol/L, CV 0.7 %
Analytical Sensitivity:
LoB (Limit of Blank): 6 nmol/L
LoD (Limit of Detection): 7 nmol/L
LoQ (Limit of Quantitation): 7 nmol/L
Linearity: 7 – 240 nmol/L
Method Comparison (Tina-quant Lipoprotein (a) Gen.2 Molarity vs. Lp(a) ELISA):
Deming regression: y = 1.023x + 0.692 nmol/L
r = 0.992
Sample Matrix Comparison (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
Reference Ranges (Median, 2.5th percentile (90 %-CI), 97.5th percentile (90 %-CI) in nmol/L):
Caucasian/White (n=425): 17.8,
§ 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).
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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.
1
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
2
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)
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
4
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 Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Leslie Patterson |
| Phone: (317) 225-8563 | |
| Email: 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: 9610126 |
| Roche Diagnostics GmbH Penzberg, Germany: 9610529 | |
| Roche 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.
6
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 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. | In vitro test for the quantitative
determination of lipoprotein (a) in human
serum and plasma on Roche/Hitachi
cobas c systems. The measurement of
Lp(a) is useful in evaluating lipid
metabolism disorders and assessing
atherosclerotic cardiovascular disease in
specific populations, when used in
conjunction with clinical evaluation and
other lipoprotein tests. |
| Assay Method | Same | Particle enhanced immunoturbidimetric
assay |
| Instrument
Platform | Same | cobas c systems |
| Sample
Type/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 standardized
against the IFCC reference material
SRM2B for nmol/L. | This method has been standardized
against an in-house reference material. |
| Calibration
Method | Same | 6-point, spline |
| Calibration
Interval | Automatic full calibration
- after reagent lot change
Full calibration - as required following quality control
procedures | Full calibration - after reagent lot change
- as required following quality control
procedures |
| Controls | Same | PreciControl Lp(a) Gen.2 |
| Measuring Range | 7-240 nmol/L | 6.0-80 mg/dL |
| Lower Limits of
Measurement | LoB (Limit of Blank): 6 nmol/L
LoD (Limit of Detection): 7 nmol/L
LoQ (Limit of Quantitation): 7 nmol/L | LoB (Limit of Blank): 3 mg/dL
LoD (Limit of Detection): 4 mg/dL
LoQ (Limit of Quantitation): 6 mg/dL |
| | Candidate Device:
Tina-quant Lipoprotein (a)
Gen.2 Molarity | Predicate Device:
Tina-quant Lipoprotein (a)
Gen.2 (K122722) |
| Method
Comparison | Method comparison between the candidate method, Tina-quant Lipoprotein (a) Gen.2
Molarity 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.
9
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.
| Endogenous
Substance | Claim
No significant interference up to |
|-------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|
| Icterus | I index of 60 for conjugated and unconjugated bilirubin
(approximate conjugated and unconjugated bilirubin concentration: 1026
µmol/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 2000
There is poor correlation between the L index (corresponds to turbidity) and
triglycerides 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 |