(622 days)
The Lp(a) Ultra assay is intended for in vitro diagnostic use in the immunoturbidimetric quantitation of lipoprotein (a) [Lp(a)] in human serum and plasma using an automated analyzer. 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.
For In Vitro Diagnostic use.
Lp(a) Ultra assay is composed by 2 ready to use liquid reagents (Reagent 1and Reagent 2) that are supplied in the following configuration: Reagent 1 fill volume 18 mL in a 20 mL wedge and Reagent 2 fill volume 9 mL in a 20 mL wedge, 1 wedge of each/kit.
The kit contains one plastic (HDPE) vial of Reagent 1 and one plastic (HDPE) vial of Reagent 2, which allows the customer to perform 86 tests (on AU680 automatic analyzer).
The provided text describes the performance testing of the Lp(a) Ultra assay, an in vitro diagnostic device, and its acceptance criteria. This is a lab-based assay, not an AI/ML medical device, and therefore the concepts of human readers, AI assistance, ground truth experts, and training/test sets as understood in AI/ML are not directly applicable in the same way. However, I can extract and present the information in a table format that parallels the requested structure for acceptance criteria and performance against those criteria.
Key takeaway: This document describes a traditional in-vitro diagnostic device, not an AI/ML based device. Therefore, many of the requested fields (e.g., number of experts, adjudication methods, MRMC studies, AI assistance) are not relevant.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criterion (Test Performed) | Target/Requirement (Implicit) | Reported Device Performance |
|---|---|---|
| Precision (Repeatability/Reproducibility) | Inter-Assay (Total Imprecision): Good precision across the concentration range. Intra-Assay (Within Run): Calculated CV% lower than 5%. | Inter-Assay: Total %CV ranged from 2.3% to 5.3% across 5 concentration levels (20 mg/dL to 100 mg/dL). Intra-Assay: Total %CV ranged from 0.5% to 4.8% across 5 concentration levels and 3 runs. All calculated CV% were lower than 5%. |
| Linearity (Analytical Measuring Range - AMR) | Demonstrate linearity up to 100 mg/dL and establish AMR. | Linear range found as 8.4 to 105.5 mg/dL (Lot 00507) and 8.4 to 103.8 mg/dL (Lot 10208). The assay is linear up to 100 mg/dL. Claimed AMR: 10 mg/dL to 100 mg/dL (based on LoQ and linearity). |
| Analytical Sensitivity/Detection Limit | Limit of Blank (LoB): Highest measurement for a blank sample within reasonable limits. Limit of Detection (LoD): Lowest analyte concentration reliably distinguished from LoB. Limit of Quantitation (LoQ): Lowest amount quantifiable with stated accuracy. | LoB: 0.7 mg/dL (for both reagent lots). Supports LoB claim of 0.7 mg/dL. LoD: 1.6 mg/dL (Lot 90266), 1.9 mg/dL (Lot 90530). Supports LoD claim of 1.9 mg/dL. LoQ: 2.5 mg/dL (Lot 90266), 3.0 mg/dL (Lot 90530). Supports LoQ claim of 3.0 mg/dL. |
| Interference (Endogenous Substances) | No significant interference from common endogenous substances (e.g., Intralipid, Triglycerides, Bilirubin, Rheumatoid Factor, Hemoglobin, Ascorbic Acid) at specified concentrations. | No interference observed for: - Intralipid® Sterile Fat Emulsion: up to 1000 mg/dL - Conjugated bilirubin: up to 60 mg/dL - Unconjugated bilirubin: up to 60 mg/dL - Rheumatoid Factor: up to 500 UI/mL - Hemoglobin: up to 1000 mg/dL - Ascorbic Acid: up to 180 mg/dL * Triglycerides: Tested up to 1000 mg/dL; no significant interference from 461 to 715 mg/dL. |
| Stability (On Board/Calibration) | Demonstrate stated on-board and calibration stability claims. | Calibration Stability: 15 days on AU 680 Analyzer. On-board stability: 30 days on AU680 analyzer. %bias for levels 1-5 within acceptable ranges (-4.8% to 5.1%). |
| Prozone Effect | No high-dose hook effect (prozone) observed within the claimed measuring range. | No Prozone effect observed up to 500.0 mg/dL. No prozone effect claimed up to the upper limit of the measuring range. |
| Method Comparison vs. Predicate Device | Demonstrate substantial equivalence in performance to the predicate device. | Correlation Coefficient (r): 0.995 (Passing & Bablok fit and Linear fit). Slope: 0.9850 (0.9706 - 1.0000) for Passing & Bablok; 0.9771 (0.9612-0.9929) for Linear fit. |
| Matrix Comparison (Serum vs. Plasma) | Demonstrate correlation between serum and various plasma types (Lithium Heparin, Sodium Heparin, Di-Potassium EDTA, Tri-Potassium EDTA). | Lithium Heparin: r=0.997, Slope=0.99 (0.95-1.03). Sodium Heparin: r=0.999, Slope=0.99 (0.95-1.01). Di-Potassium EDTA: r=0.997, Slope=0.97 (0.95-1.01). Tri-Potassium EDTA: r=0.998, Slope=0.99 (0.95-1.03). |
2. Sample size used for the test set and the data provenance:
- Precision (Repeatability/Reproducibility):
- Inter-Assay: 5 samples at different concentrations. 2 replicates per sample, 2 runs per day, for 28 testing days. (Total of 280 measurements per sample level over the entire study for 5 levels? The specific number of measurements is implied but not explicitly stated as 'n=X' for the total dataset.)
- Intra-Assay: 5 samples at different concentrations. 20 replicates per sample, run on 3 different runs. (Total of 300 measurements over the entire study: 5 samples x 20 replicates x 3 runs).
- Linearity: 2 different reagent lots. No specific sample count is given, but "dilution series" are implied.
- Analytical Sensitivity (LoB, LoD, LoQ):
- LoB: 4 saline samples (zero-analyte) for two reagent lots, tested in 5 replicates in 3 different runs. (Total of 60 measurements per lot).
- LoD & LoQ: The guidelined CLSI EP17-A2 was followed, but specific sample counts were not explicitly stated for these sections beyond the general method.
- Interference: "Low: ~30 mg/dL" and "High: ~50 mg/dL" Lp(a) concentrations. Two aliquots of serum pool per concentration. Tested in different replicates for paired difference and then diluted. Specific numbers of individual patient samples tested for interference effects for each substance are not provided.
- Stability (On Board Calibration): 5 samples at different concentrations (20 mg/dL to 100 mg/dL).
- Prozone Study: Last calibrator level used to reach a high concentration (approx. 500.0 mg/dL). Sample diluted in saline.
- Method Comparison vs. Predicate Device: Not explicitly stated but usually involves a significant number of patient samples covering the assay range to demonstrate correlation. The CLSI document EP09c 3rd Edition was followed.
- Matrix Comparison:
- Lithium Heparin: 57 serum and Lithium Heparin plasma samples "derived from the same patients", tested in duplicate.
- Sodium Heparin: 58 serum and Sodium Heparin plasma samples "derived from the same patients", tested in duplicate.
- Di-Potassium EDTA: 57 serum and Di-Potassium EDTA plasma samples "derived from the same patients", tested in duplicate.
- Tri-Potassium EDTA: 56 serum and Tri-Potassium EDTA plasma samples "derived from the same patients", tested in duplicate.
Data Provenance: The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective, beyond stating that they used "human serum and plasma" samples. Given it's a 510(k) submission from an Italian company for an in vitro diagnostic device, the samples are typically human biological samples obtained under ethical guidelines, often from healthy volunteers or patient populations relevant to the assay's indication.
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):
Not applicable for this type of IVD device. The "ground truth" for quantitative assays is established by reference methods, traceable calibrators, and robust analytical procedures, not through expert consensus like in image interpretation. The performance is assessed by direct measurement and comparison to established analytical performance metrics and standard reference materials.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. Adjudication methods are typically used in clinical trials involving human interpretation of medical images or symptoms where there might be inter-reader variability. For an IVD assay, performance is determined by instrumental measurements and statistical analysis against predefined acceptance criteria.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. This is an in vitro diagnostic device, not an AI/ML-driven analysis tool for human readers. No human interpretation or AI assistance is involved in its direct operation or intended use.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable in the context of an AI algorithm. The device, Lp(a) Ultra, is a standalone reagent (assay) used on an automated analyzer (Beckman Coulter AU680). Its performance is inherently "standalone" in that it measures analyte concentration without human interpretation of raw signals; humans perform the testing and interpret the numerical results from the analyzer.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The "ground truth" for this in vitro diagnostic assay is established through:
- Reference standards and calibrators: Used to define known concentrations of Lp(a).
- Defined analytical methods: Following recognized guidelines (e.g., CLSI EP05-A3, EP15-A3, EP06, EP17-A2, EP07, EP25-A, EP09c) for precision, linearity, sensitivity, interference, etc.
- Comparison to a legally marketed predicate device: "Ground truth" for demonstrating substantial equivalence is the performance of the predicate device (Diazyme Lipoprotein (a) Assay).
- Known concentrations in spiked samples or characterized biological samples: Used for studies like linearity and interference.
8. The sample size for the training set:
Not applicable. This is not an AI/ML device, so there is no "training set" in that sense. The device is a chemical reagent kit with defined analytical characteristics.
9. How the ground truth for the training set was established:
Not applicable. See point 8.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
December 22, 2022
SENTINEL CH. S.p.A. Patricia Dupé Head of Quality System Via Robert Koch 2 Milan, 20152 Italy
Re: K211058
Trade/Device Name: Lp(a) Ultra Regulation Number: 21 CFR 866.5600 Regulation Name: Low-Density Lipoprotein Immunological Test System Regulatory Class: Class II Product Code: DFC Dated: August 5, 2022 Received: August 5, 2022
Dear Patricia Dupé:
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.
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
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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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-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 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-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-regulatoryassistance/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, Digitally signed by Paula Caposino -S Date: 2022.12.22 Paula Caposino, Ph.D. Acting 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2023 See PRA Statement below.
510(k) Number (if known) K211058
Device Name Lp(a) Ultra
Indications for Use (Describe)
The Lp(a) Ultra assay is intended for in vitro diagnostic use in the immunoturbidimetric quantitation of lipoprotein (a) [Lp(a)] in human serum and plasma using an automated analyzer. 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.
For In Vitro Diagnostic use.
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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510(k) SUMMARY
1. Applicant Name
SENTINEL CH. S.p.A. Via Robert Koch, 2 Milano (MI) 20152, Italy +39 02 345 514 1
Primary contact person for all communications:
Patricia Dupé Head of Quality System Phone: +39 02 34 551 496 Fax: +39 02 34 551 464 Email: patriciadupe@sentinel.it
2. Device Name and Classification
Trade name: Lp(a) Ultra Device Classification: Class II Regulation: 21CFR 866.5600 Regulation Name: Low-density lipoprotein immunological test system Product Code: DFC Device Name: Lipoprotein, Low-Density, Antigen, Antiserum, Control Medical Specialty: Immunology
3. Predicate Device
Diazyme Lipoprotein (a) Assay (K180074)
4. Indications for Use
The Lp(a) Ultra assay is intended for in vitro diagnostic use in the immunoturbidimetric quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma using an automated analyzer. 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.
For In Vitro Diagnostic use.
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5. Intended Use
The Lp(a) Ultra assay is intended for in vitro diagnostic use in the immunoturbidimetric quantitative determination of lipoprotein (a) [Lp(a)] in human serum and plasma using an automated analyzer. 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.
For In Vitro Diagnostic use.
6. Description
Lp(a) Ultra assay is composed by 2 ready to use liquid reagents (Reagent 1and Reagent 2) that are supplied in the following configuration: Reagent 1 fill volume 18 mL in a 20 mL wedge and Reagent 2 fill volume 9 mL in a 20 mL wedge, 1 wedge of each/kit.
The kit contains one plastic (HDPE) vial of Reagent 1 and one plastic (HDPE) vial of Reagent 2, which allows the customer to perform 86 tests (on AU680 automatic analyzer).
7. Principles of the Procedure
Lp(a) Ultra is a latex-based immunoturbidimetric assay developed to measure Lp(a) levels in serum and plasma.
When an antigen-antibody reaction occurs between Lp(a) in a sample and anti-Lp(a) antibody which has been adsorbed to latex particles, agglutination results. This agglutination is detected as an absorbance change, with the magnitude of the change being proportional to the quantity of La(a) contained in the sample.
8. Comparison with Predicate Device
The comparison between Lp(a) Ultra and the predicate device Diazyme Lipoprotein (a) Assay is reported in Table 8.1.
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Table 8.1. Comparison Lp(a) Ultra vs. Predicate Device Diazyme Lipoprotein (a) Assay
| Characteristics | Subject Device | Predicate Device K180074 |
|---|---|---|
| Lp(a) Ultra | Diazyme Lipoprotein (a) Assay | |
| Technical Characteristics | ||
| Classification | Regulation Description: Low-density lipoproteinimmunological test system | Same |
| Method Principle | Quantitative immunoturbidimetric assay | Same |
| Intended Use | The Lp(a) assay is intended for in vitro diagnostic use inthe immunoturbidimetric quantitative determination oflipoprotein (a) [Lp(a)] in human serum and plasma usingan automated analyzer.The measurement of Lp(a) is useful in evaluating lipidmetabolism disorders and assessing atheroscleroticcardiovascular disease in specific populations, when usedin conjunction with clinical evaluation.For In Vitro Diagnostic use. | The Diazyme Lipoprotein (a) Assay is intended as a latex particleenhanced immunoturbidimetric assay for the in vitro quantitativedetermination of Lipoprotein (a) [Lp(a)] concentration in humanserum or plasma on Clinical Chemistry Systems. Themeasurement of Lipoprotein (a) is useful in evaluating lipidmetabolism disorders and assessing atheroscleroticcardiovascular diseases in specific populations, when used inconjunction with clinical evaluation. For in vitro diagnostic useonly. |
| Analyte Measured | Lipoprotein (a) | Same |
| Instrument Used | Beckman Coulter AU680 | Ortho Clinical Diagnostics VITROS 4600 |
| Measurement | Quantitative | Same |
| Specimen Type | Serum, plasma (Na-heparin, Li-heparin, K2-EDTA, K3-EDTA) | Serum, plasma (Li-Heparin, K2EDTA) |
| Reference Values | Lp(a) < 30 mg/dL | 10 mg/dL < Lp(a) < 30 mg/dL |
| Reagents | Two reagents | Same |
| Format | Liquid | Same |
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SENTINEL CH. SpA
Lp(a) Ultra - Quantitative immunoturbidimetric assay of Lipoprotein (a) in serum and plasma
Traditional 510(k) K211058
| Characteristics | Subject DeviceLp(a) Ultra | Predicate Device K180074Diazyme Lipoprotein (a) Assay |
|---|---|---|
| Analytical MeasuringRange | 10 - 100 mg/dL | 5.4 - 100 mg/dL |
| Performance Characteristics | ||
| Storage Temperature | 2-8°C | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
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9. PERFORMANCE TESTING SUMMARY
All performance were established using the Beckman Coulter AU680 analyzer.
Precision (Repeatability/Reproducibility) 9.1.
9.1.1. Inter-Assay Precision (Total Imprecision)
The Inter-Assay Precision study verifies the agreement between indications or measured quantity values obtained by replicates measurements on the same or similar objects under specified conditions.
The precision was determined on the basis of CLSI EP05-A3 Guideline (Evaluation of Precision of Quantitative Measurement Procedures).
Five samples were used at different concentration ranging from 20 mg/dL to 100 mg/dL. After calibration at Time zero, 2 replicates of each sample were performed on 2 different runs for day. The assay was calibrated at Time 0 and day 15. The procedure was repeated for 28 testing days.
9.1.1.1. Results
A summary of the results is presented in Table 9.1.1.
| Reagent | Material | Total %CV |
|---|---|---|
| Lot 90530 | Level 1 | 4.6% |
| Lot 90530 | Level 2 | 3.2% |
| Lot 90530 | Level 3 | 5.3% |
| Lot 90530 | Level 4 | 3.3% |
| Lot 90530 | Level 5 | 2.3% |
Table 9.1.1. Inter-Assay Precision Results
The data show good precision across the concentration range from 20 to 100 mg/dL.
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9.1.2. Intra-Assay Precision (Within Run)
The Intra-Assay Precision study verifies the precision and the trueness of the method relative to the assigned values of materials with known concentrations.
The Intra-Assay Precision was determined on the basis of CLSI EP15-A3 Guideline (User Verification of Precision and Estimation of Bias).
Five samples were used at different concentration ranging from 20 mg/dL to 100 mg/dL. After calibration, 20 replicates of each sample were run on 3 different runs (each run with a new calibration).
9.1.2.1. Results
A summary of the results is presented in Table 9.1.2.
| Reagent | Run | Material | Concentrationmg/dL | Total%CV | SDmg/dL |
|---|---|---|---|---|---|
| Lot 90266 | 1 | Level 1 | 19.0 | 3.5 | 0.7 |
| Level 2 | 47.0 | 2.7 | 1.3 | ||
| Level 3 | 10.6 | 3.3 | 0.4 | ||
| Level 4 | 32.7 | 1.3 | 0.4 | ||
| Level 5 | 100.9 | 0.7 | 0.8 | ||
| Lot 90266 | 2 | Level 1 | 18.9 | 3.7 | 0.7 |
| Level 2 | 45.9 | 1.9 | 0.9 | ||
| Level 3 | 10.7 | 4.8 | 0.5 | ||
| Level 4 | 32.8 | 1.5 | 0.5 | ||
| Level 5 | 97.7 | 0.5 | 0.5 | ||
| Lot 90266 | 3 | Level 1 | 19.1 | 2.8 | 0.5 |
| Level 2 | 46.0 | 1.1 | 0.5 | ||
| Level 3 | 11.1 | 4.4 | 0.5 | ||
| Level 4 | 33.6 | 1.6 | 0.5 | ||
| Level 5 | 99.4 | 0.8 | 0.8 |
Table 9.1.2. Intra-Assay Precision Results
All the calculated CV% are lower than 5%.
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9.2. Linearity
9.2.1. Linearity - Analytical Measuring Range
The study was performed to establish the Upper Limit of Analytical Measurement Range (AMR) based upon the linearity of the Lp(a) assay on Beckman Coulter AU680.
Linearity was evaluated using guideline CLSI EP06 (Evaluation of the Linearity of Quantitative Measurement Procedures, 2nd Edition
Results 9.2.1.1.
A summary of the results is presented in Table 9.2.1.
| Reagent | Tested range (mg/dL) | Range found as Linear (mg/dL) |
|---|---|---|
| Lot 00507 | 1.0 to 139.0 | 8.4 to 105.5 |
| Lot 10208 | 1.2 to 131.5 | 8.4 to 103.8 |
Table 9.2.1. Linearity Results
The results demonstrate that the assay is linear up to 100 mg/dL. The upper limit of the AMR is 100 mg/dL.
The AMR is claimed as 10 mg/dL to 100 mg/dL as resulted from sensitivity (LoQ) and from linearity studies.
Analytical Sensitivity/Detection Limit 9.3.
9.3.1. Limit of Blank (LoB) Study
The Limit of Blank (LoB) study was performed to determine the highest measurement result that is likely to be observed (with a stated probability) for a blank sample.
The LoB study was performed using the guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2
For two different reagent lots, 4 saline samples (zero-analyte samples) were tested in 5 replicates in three different runs, for a total of 60 measurements for each lot.
9.3.1.1. Results
A summary of the results is presented in Table 9.3.1.
| Reagent | Limit of Blank (LoB)mg/dL |
|---|---|
| Lot 90266 | 0.7 |
| Lot 90530 | 0.7 |
Table 9.3.1. Limit of Blank Results
The observed Limit of Blank supports the LoB claim of 0.7 mg/dL.
| 510(k) SUMMARY | Page 7 of 13 |
|---|---|
| ---------------- | -------------- |
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9.3.2. Limit of Detection (LoD) Study
The Limit of Detection (LoD) is the lowest analyte concentration likely to be reliably distinguished from the LoB and at which detection is feasible.
The LoD was determined on the basis of CLSI EP17-A2 Guideline (Evaluation of detection capability for clinical laboratory measurement procedures).
9.3.2.1. Results
A summary of the results is presented in Table 9.3.2.
Table 9.3.2. Limit of Detection Results
| Reagent | Limit of Detection (LoD) mg/dL |
|---|---|
| 90266 | 1.6 |
| 90530 | 1.9 |
The Limit of Detection is chosen to be the highest value obtained. The LoD value observed supports the claim of 1.9 mg/dL.
9.3.3. Limit of Quantitation (LoQ) Study
The Limit of Quantitation (LoQ) is the lowest amount of a measure and in a material that can be quantitatively determined with stated accuracy (as total error or as independent requirements for bias and precision), under stated experimental conditions.
The LoQ was determined on the basis of CLSI EP17-A2 Guideline (Evaluation of detection capability for clinical laboratory measurement procedures).
9.3.3.1. Results
A summary of the results is presented in Table 9.3.3.
Table 9.3.3. Limit of Quantitation Results
| Reagent | Limit of Quantification(LoQ) mg/dL |
|---|---|
| Lot 90266 | 2.5 |
| Lot 90530 | 3.0 |
The LoQ observed supports the claim of 3.0 mg/dL.
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Traditional 510(k)
9.4. Interference
9.4.1. Endogenous Interferences Study
The Interferences Study was performed to evaluate the influence some endogenous substance on the performances of the product.
The study was performed on the basis of EP07 3d Edition - Interference Testing in Clinical Chemistry.
The interference was evaluated at the following Lp(a) concentrations:
Low: ~ 30 mg/dL
High: ~ 50 mg/dL
For each concentration 2 aliquots of serum pool were prepared:
- Test Sample (High Test Sample) Σ 1st aliquot:
-
2nd aliquot: Control Sample (Low Test Sample)
The study was divided in two procedures:
-
- Paired Difference Tests
Test Sample and Control Sample were tested in different replicates. If there is no interferences the study was concluded. If Interference is confirmed, proceed with the 'Interference test'
- Paired Difference Tests
-
- Interference test
The Test Sample aliquots were diluted using the Control Sample to obtain additional dilution levels in the ratio ranging from 100% to 0%
- Interference test
9.4.1.1. Results
A summary of the results is presented in Table 9.4.1.
| Interfering substance | Testedconcentrationup to | ObservedconcentrationwithoutInterferencesPool Low | ObservedconcentrationwithoutInterferencesPool High |
|---|---|---|---|
| Intralipid® Sterile FatEmulsion | 1000 mg/dL | 1000 mg/dL | 1000 mg/dL |
| Triglycerides | 1000 mg/dL | 715 mg/dL * | 715 mg/dL * |
| Conjugated bilirubin | 60 mg/dL | 60 mg/dL | 60 mg/dL |
| Unconjugated bilirubin | 60 mg/dL | 60 mg/dL | 60 mg/dL |
| Rheumatoid Factor | 500 UI/mL | 500 UI/mL | 500 UI/mL |
| Hemoglobin | 1000 mg/dL | 1000 mg/dL | 1000 mg/dL |
| Ascorbic Acid | 180 mg/dL | 180 mg/dL | 180 mg/dL |
Table 9.4.1. Interferences Results Summary
- Triglycerides was tested in patient serum samples without significant interference at triglycerides concentration ranging from 461 to 715 mg/dL.
| 510(k) SUMMARY | Page 9 of 13 |
|---|---|
| ---------------- | -------------- |
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9.5. Stability
9.5.1. On Board Calibration Study
The Stability study allows to verify the On Board and the Calibration Stability of the product.
The On Board and the Calibration Stability were determined on the basis of CLSI EP25-A Guideline (Evaluation of Stability of in Vitro Diagnostics Reagents).
For the study, 5 samples were used at different concentration ranging from 20 mg/dL to 100 mg/dl.
9.5.1.1. Results
A summary of the results is presented in Table 9.5.1.
| Reagent | Material | %biasMin | % biasMax |
|---|---|---|---|
| Lot 90530 | Level 1 | -2.7% | 5.1% |
| Level 2 | -0.7% | 1.4% | |
| Level 3 | -4.8% | 0.7% | |
| Level 4 | -3.4% | 1.0% | |
| Level 5 | -1.3% | 1.1% |
Table 9.5.1. On Board Calibration Results
The Calibration Stability claim is 15 days on the AU 680 Analyzer. The on-board stability claim is 30 days on the AU680 analyzer.
9.6. Other Analytical Performance
9.6.1. Prozone Study
The High Dose Hook Effect (Prozone) study was performed to determine the analyte concentration at which false negatives results may occur.
For the study, the last calibrator level of calibrator set reconstituted with 191 µL was used to reach a high concentration (approx. 500.0 mg/dL).
The sample was diluted in saline to obtain some concentration points within the analytical measuring range.
9.6.1.1. Results
No Prozone effect was observed up to concentration of 500.0 mg/dL. No prozone effect up to the upper limit of the measuring range is claimed.
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9.7. Comparison Studies
9.7.1. Method Comparison vs. Predicate Device
Purpose of this study is to evaluate the performances of Lp(a) Ultra assay on Beckman Coulter AU680 Analyzer, compared to the predicate device Diazyme® Lipoprotein (a), REF DZ131B-K, on VITROS® 4600, Ortho Clinical Diagnostics.
The method comparison study was performed based on guidance from the CLSI document EP09c 3rd Edition.
9.7.1.1. Results
A summary of the results is presented in Table 9.7.1.
| Results- Passing & Bablok fit | Results- Linear fit- | |
|---|---|---|
| r | 0.995 | 0.995 |
| Slope | 0.9850(0.9706 - 1.0000) | 0.9771(0.9612 - 0.9929) |
Table 9.7.1. Method Comparison vs. Predicate Device Results
9.7.2. Matrix Comparison - Lithium Heparin
This study was performed to demonstrate correlation between Serum samples and Plasma Lithium Heparin samples.
The Matrix Comparison study was performed based on guidance from the CLSI document EP09c 3rd Edition.
57 serum and Lithium Heparin plasma samples, derived from the same patients were tested in duplicate.
9.7.2.1. Results
A summary of the results is presented in Table 9.7.2.
Table 9.7.2. Matrix Comparison - Lithium Heparin Results
| Results- Passing & Bablok fit - | Results- Linear fit- | |
|---|---|---|
| r | 0.997 | 0.997 |
| Slope | 0.99(0.95 - 1.03) | 0.98(0.95 – 1.00) |
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9.7.3. Matrix Comparison - Sodium Heparin
This study was performed to demonstrate correlation between Serum samples and Plasma Sodium Heparin samples.
The method comparison study was performed based on guidance from the CLSI document EP09c 3tt Edition.
58 serum and Sodium Heparin plasma samples, derived from the same patients were tested in duplicate.
Results 9.7.3.1.
A summary of the results is presented in Table 9.7.3.
| Results- Passing & Bablok fit - | Results- Linear fit- | |
|---|---|---|
| r | 0.999 | 0.999 |
| Slope | 0.99(0.95 – 1.01) | 0.99(0.97 - 1.00) |
Table 9.7.3. Matrix Comparison - Sodium Heparin Results
9.7.4. Matrix Comparison - Di-Potassium EDTA
This study was performed to demonstrate correlation between Serum samples and Plasma Di-Potassium EDTA samples.
The Matrix Comparison study was performed based on guidance from the CLSI document EP09c 3rd Edition.
57 serum and Di-Potassium EDTA plasma samples, derived from the same patients were tested in duplicate.
9.7.4.1. Results
A summary of the results is presented in Table 9.7.4.
Table 9.7.4. Matrix Comparison - Di-Potassium EDTA Results
| Results- Passing & Bablok fit - | Results- Linear fit- | |
|---|---|---|
| r | 0.997 | 0.997 |
| Slope | 0.97(0.95 - 1.01) | 0.98(0.96 - 1.00) |
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9.7.5. Matrix Comparison - Tri-Potassium EDTA
This study was performed to demonstrate correlation between Serum samples and Plasma Tri-Potassium EDTA samples.
The method comparison study was performed based on guidance from the CLSI document EP09c 3rd Edition.
56 serum and Tri-Potassium EDTA plasma samples, derived from the same patients were tested in duplicate.
9.7.5.1. Results
A summary of the results is presented in Table 9.7.5.
| Results | Results | |
|---|---|---|
| - Passing & Bablok fit - | - Linear fit- | |
| r | 0.998 | 0.998 |
| Slope | 0.99(0.95 - 1.03) | 0.99(0.98 - 1.01) |
Table 9.7.5. Matrix Comparison – Tri-Potassium EDTA Results
CONCLUSIONS 10.
Testing results indicate that the proposed device Lp(a) Ultra is substantially equivalent to the predicate device.
| 510(k) SUMMARY | Page 13 of 13 |
|---|---|
| ---------------- | --------------- |
§ 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).