(259 days)
The Cystatin C assay is an in vitro diagnostic test used in the quantitative immunoturbidimetric determination of cystatin C in human serum and plasma on the Alinity c system.
Measurement of cystatin C aids in the diagnosis and treatment of renal diseases.
For laboratory professional use only.
The Cystatin C assay is an automated clinical chemistry assay.
Cystatin C is a particle-enhanced turbidimetric immunoassay (PETIA) developed to accurately and reproducibly measure cystatin C levels in serum and plasma. Latex particles coated with anti-human cystatin C antibody agglutinate when mixed with sample containing human cystatin C. The change in absorbance due to agglutination of the reaction mixture is proportional to the quantity of human cystatin C in the sample.
The provided text is a 510(k) clearance letter for an in vitro diagnostic test (Cystatin C assay), not an AI/ML-driven medical device. Therefore, the information requested for AI/ML device studies (such as MRMC studies, expert adjudication, training set ground truth, etc.) is not applicable to this document.
However, I can extract and present the performance acceptance criteria and reported device performance from the provided document, even though they relate to a traditional laboratory assay rather than an AI/ML model.
Here's an interpretation based on the provided text for a traditional in vitro diagnostic device:
Based on the provided FDA 510(k) clearance letter for the Cystatin C Test System, the device is a quantitative immunoturbidimetric assay for the determination of cystatin C in human serum and plasma. The performance of this device was demonstrated through various nonclinical studies.
1. Table of Acceptance Criteria and Reported Device Performance
For in vitro diagnostic tests like the Cystatin C assay, "acceptance criteria" are typically defined by ranges or thresholds for performance characteristics such as precision, accuracy (bias), linearity, and limits of detection. The document describes the reported performance measured during the studies, and implicitly, these figures met the internal acceptance criteria set by the manufacturer (and approved by the FDA for clearance).
Here's a summary of the reported device performance:
| Performance Characteristic | Acceptance Criteria (Implicit from Industry Standards/Predicate) | Reported Device Performance (Cystatin C Assay) |
|---|---|---|
| Analytical Measuring Interval (AMI) | Defined range of accurate and precise measurement | 0.30 – 10.00 mg/L |
| Extended Measuring Interval (EMI) | Range accessible via dilution/spiking | 10.00 – 40.00 mg/L |
| Reportable Interval | Overall range of reportable results | 0.30 – 40.00 mg/L |
| Within-Laboratory Precision (Repeatability) | Expected low variability | Control Level 1: 0.81 mg/L Mean, 1.0%CV Control Level 2: 4.11 mg/L Mean, 0.6%CV Panel A: 0.49 mg/L Mean, 1.7%CV Panel B: 0.92 mg/L Mean, 0.8%CV Panel C: 5.89 mg/L Mean, 0.5%CV Panel D: 8.95 mg/L Mean, 0.8%CV |
| Within-Laboratory Precision (Total) | Expected low variability over time | Control Level 1: 1.7%CV Control Level 2: 1.0%CV Panel A: 1.8%CV Panel B: 0.9%CV Panel C: 0.6%CV Panel D: 1.0%CV |
| Overall Reproducibility | Expected low variability across sites/lots | Control Level 1: 2.0%CV Control Level 2: 1.1%CV Panel 1: 5.4%CV Panel 2: 1.6%CV Panel 3: 1.6%CV |
| Accuracy (Bias vs. Reference Material) | Acceptable low bias to a certified reference | Ranged from 1.3% to 1.8% across all reagent and calibrator lots relative to ERM-DA471/IFCC. |
| Linearity | Demonstrated proportional response across AMI | Linear across 0.30 to 10.00 mg/L (AMI). |
| Limit of Blank (LoB) | Lowest detectable signal for a blank sample | 0.03 mg/L |
| Limit of Detection (LoD) | Lowest concentration detectable with 95% probability | 0.05 mg/L |
| Limit of Quantitation (LoQ) | Lowest concentration meeting 25% total allowable error | 0.30 mg/L |
| Hook Effect (Prozone Effect) | No false low results at high concentrations | No prozone effect observed up to 40.00 mg/L. |
| Interference (Endogenous Substances) | No significant interference at specified levels | No significant interference observed for Bilirubin (60 mg/dL), Hemoglobin (1000 mg/dL), Total protein (10.2-11.8 g/dL), Triglycerides (1500 mg/dL). Some interference noted for high Rheumatoid factor and very high Total protein. |
| Interference (Exogenous Substances) | No significant interference at specified levels | No significant interference observed for 16 common drugs (e.g., Acetaminophen, Ibuprofen, Ascorbic acid, Cyclosporin, etc.) at specified therapeutic/toxic levels. |
| Correlation with Comparator Assay | Strong correlation with predicate/comparable method | Correlation Coefficient: 1.00 (Serum, n=161) vs. Comparator Cystatin C assay. |
| Matrix Comparison | Acceptable for various specimen types | Acceptable for Serum, Serum separator, Dipotassium EDTA, Lithium heparin, Lithium heparin separator, Sodium heparin, Tripotassium EDTA plasma. |
| Reference Interval (Expected Values) | Established range for healthy individuals | Adult: 0.59–1.28 mg/L (2.5th to 97.5th percentile) |
Study Details (Relevant to IVD, not AI/ML)
The following points are addressed as much as possible for an in vitro diagnostic device, noting where the requested AI/ML specific information is not applicable.
-
Sample sizes used for the test set and the data provenance:
- Precision/Reproducibility:
- Within-Laboratory Precision: 80 replicates per sample/control (2 replicates/day for 20 days) for 2 controls and 4 human serum panels.
- Reproducibility: 240 replicates per sample/control (4 replicates, twice/day for 5 days at 3 sites) for 2 controls and 3 human serum panels.
- Accuracy (Bias): Not specified as a separate sample size, but involved testing across 2 reagent lots and 2 calibrator lots.
- Linearity: Not specified as a number of distinct samples, but assessed over a range of concentrations.
- Lower Limits of Measurement (LoB, LoD, LoQ): ≥ 60 replicates of zero-analyte samples for LoB, and ≥ 60 replicates of low-analyte level samples for LoD/LoQ.
- Analytical Specificity (Interference): Each substance tested at 2 analyte levels.
- Method Comparison: 161 serum samples.
- Matrix Comparison: Not specified as a specific number, but evaluated across various tube types.
- High Dose Hook: Not specified as a specific number of samples, but tested up to 40.00 mg/L.
- Expected Values (Reference Interval): 250 apparently healthy individuals (105 females, 145 males) with eGFR > 80, aged 18 to 69 years.
Data Provenance: The document does not explicitly state the country of origin for the clinical samples. The studies are described as "nonclinical performance" studies, meaning they evaluate the analytical performance of the assay itself, rather than diagnostic accuracy in a clinical setting with patient outcomes. These are typically prospective studies conducted in a controlled lab environment.
- Precision/Reproducibility:
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable for this in vitro diagnostic device. Ground truth for analytical performance studies of IVDs is established by the known concentration of analytes in reference materials, calibrators, and characterized control samples, or by comparison to a well-established reference or predicate method. It does not involve expert readers or their consensus.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable for this in vitro diagnostic device. Adjudication methods are relevant for subjective image-based assessments or clinical diagnoses where human interpretation varies. This product is a quantitative chemical assay.
-
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 for this in vitro diagnostic device. MRMC studies are for evaluating the impact of AI on human reader performance, typically in radiology or similar interpretive fields. This device performs automated measurements.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Analogous concept applies. The performance data presented (precision, accuracy, linearity, limits of detection, etc.) are the standalone performance of the assay on the Alinity c system. It demonstrates the device's ability to measure Cystatin C without human interpretation of the analytical signal.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the analytical performance studies, the ground truth was established by:
- Certified reference materials: Specifically, ERM-DA471/IFCC for assay standardization and accuracy validation.
- Preparation of known concentrations: Through spiking or dilution of samples to evaluate linearity and limits of measurement.
- Comparison to a validated comparator assay: For method comparison (Cystatin C on Alinity c vs a Comparator Cystatin C assay).
- Characterized control materials: For precision and reproducibility studies.
- Established healthy population studies: For determining the reference interval.
- For the analytical performance studies, the ground truth was established by:
-
The sample size for the training set:
- Not applicable in the AI/ML sense. This is a traditional chemical assay, not an AI/ML model that undergoes a "training" phase with data. The assay's parameters are developed through conventional analytical chemistry principles and validated through the nonclinical performance studies detailed.
- Development would involve formulation and optimization studies, but not "training data" in the AI sense.
-
How the ground truth for the training set was established:
- Not applicable for this in vitro diagnostic device. As noted above, there is no "training set" in the AI/ML context for a traditional immunoturbidimetric assay. The "ground truth" for developing such an assay would be based on fundamental chemical principles, known concentrations of analytes, and established analytical chemistry standards.
FDA 510(k) Clearance Letter - Cystatin C Test System
Page 1
U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov
Doc ID # 04017.07.05
May 16, 2025
SENTINEL CH. S.p.A.
Patricia Dupé
Head of Quality System
Via Robert Koch, 2
Milan (MI), 20152, Italy
Re: K242585
Trade/Device Name: Cystatin C
Regulation Number: 21 CFR 862.1225
Regulation Name: Creatinine Test System
Regulatory Class: Class II
Product Code: NDY
Dated: April 10, 2025
Received: April 10, 2025
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 (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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K242585 - Patricia Dupé
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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 (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-safety-reporting-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-devices/device-advice-comprehensive-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-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.
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K242585 - Patricia Dupé
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For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/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-devices/device-advice-comprehensive-regulatory-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
Page 4
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
Indications for Use
See PRA Statement below.
510(k) Number (if known)
K242585
Device Name
Cystatin C
Indications for Use (Describe)
The Cystatin C assay is an in vitro diagnostic test used in the quantitative immunoturbidimetric determination of cystatin C in human serum and plasma on the Alinity c system.
Measurement of cystatin C aids in the diagnosis and treatment of renal diseases.
For laboratory professional use only.
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
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."
FORM FDA 3881 (8/23)
Page 1 of 1
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SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 1 of 12
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
I. 510(k) Number
II. 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
Secondary contact person for all communications:
Alessia Moiana
Sr. Regulatory Affairs Specialist
Phone: +39 02 34 551 494
Email: alessiamoiana@sentinel.it
Date Summary Prepared: May 15, 2025
III. Device Name and Classification
Trade name: Cystatin C
Device Classification: Class II
Regulation Description: Creatinine test system
Regulation Number: 862.1225
Product Code: NDY
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SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 2 of 12
IV. Predicate Device
Tina-quant Cystatin C Gen.2 (K161817)
V. Description of Device
A. Principles of the Procedure
The Cystatin C assay is an automated clinical chemistry assay.
Cystatin C is a particle-enhanced turbidimetric immunoassay (PETIA) developed to accurately and reproducibly measure cystatin C levels in serum and plasma. Latex particles coated with anti-human cystatin C antibody agglutinate when mixed with sample containing human cystatin C. The change in absorbance due to agglutination of the reaction mixture is proportional to the quantity of human cystatin C in the sample.
Assay standardization
The Cystatin C assay on Alinity c system is aligned to the certified reference material ERM-DA471/IFCC.
The Cystatin C Calibrators are manufactured gravimetrically and are referenced to European Reference Material ERM-DA471/IFCC at each concentration level.
B. Reagent
The various configurations of the Cystatin C for Alinity c Reagent Kit are described below.
| List Number | 06T3220 | 06T3230 |
|---|---|---|
| Tests per cartridge | 100 | 250 |
| Number of cartridges per kit | 2 | 2 |
| Tests per kit | 200 | 500 |
| Reagent (R1) | 20.8 mL | 46.5 mL |
| Reagent (R2) | 7.5 mL | 13.7 mL |
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Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 3 of 12
Volumes (mL) listed in the table above indicate the volume per cartridge.
Each Cystatin C cartridge contains 2 ready to use liquid reagents (R1 and R2).
| Active Ingredients | Concentration |
|---|---|
| Reagent 2: latex particles coated with rabbit IgG against human cystatin C | 0.09% |
Inactive ingredients:
Reagent 1: buffer and stabilizers. Preservative: sodium azide (< 0.1%)
Reagent 2: buffer and stabilizers. Preservative: sodium azide (< 0.1%)
VI. Indications for Use/Intended Use of the Device
The Cystatin C assay is an in vitro diagnostic test used in the quantitative immunoturbidimetric determination of cystatin C in human serum and plasma on the Alinity c system.
Measurement of cystatin C aids in the diagnosis and treatment of renal diseases.
For laboratory professional use only.
VII. Comparison of Technological Characteristics
The similarities and differences between the subject device (Cystatin C, 06T32) and the predicate device (Roche Tina-quant Cystatin C Gen.2) are presented in the table below.
| Subject Device: Cystatin C | Predicate Device: Roche Tina-quant Cystatin C Gen.2 | |
|---|---|---|
| General Device Characteristic Similarities | ||
| Intended Use/Indications for Use | The Cystatin C assay is an in vitro diagnostic test used in the quantitative immunoturbidimetric determination of cystatin C in human serum and plasma on the Alinity c system. Measurement of cystatin C aids in the diagnosis and treatment of renal diseases. For laboratory professional use only. | In vitro test for the quantitative determination of cystatin C in human serum and plasma on Roche/Hitachi cobas c systems. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases. |
| Methodology | Immunoturbidimetric | Same |
| Principal of Operation | Particle-enhanced turbidimetric immunoassay | Same |
| Specimen Type | Human serum and plasma | Same |
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SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 4 of 12
| Subject Device: Cystatin C | Predicate Device: Roche Tina-quant Cystatin C Gen.2 | |
|---|---|---|
| Measurement Type | Quantitative | Same |
| Tube Type | Serum, Li-heparin, Na-heparin, K2-, and K3- EDTA plasma | Serum, Li-heparin, K2-, and K3-EDTA plasma |
| Standardization | This method has been standardized against ERM-DA471/IFCC. | Same |
| General Device Differences | ||
| Measuring Interval | Analytical Measuring Interval (AMI): 0.30–10.00 mg/LExtended Measuring Interval (EMI): 10.00–40.00 mg/LReportable Range (RI): 0.30–40.00 mg/L | Measuring Range: 0.40–6.80 mg/LExtended Measuring Range: 6.80–10.20 mg/L |
| Hook Effect | No prozone effect was observed up to 40.00 mg/L. | No false result occurs up to a cystatin C concentration of 12 mg/L. |
| Lower Limits of Measurement | Limit of Blank: 0.03 mg/LLimit of Detection: 0.05 mg/LLimit of Quantitation: 0.30 mg/L | Limit of Blank: 0.30 mg/LLimit of Detection: 0.40 mg/LLimit of Quantitation: 0.40 mg/L |
| Platform | Alinity c system | Roche/Hitachi cobas c 501 |
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SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
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VIII. Summary of Nonclinical Performance
A. Reportable Interval
Based on representative data for the limit of quantitation (LoQ), the ranges over which results can be reported are provided below in accordance with Clinical and Laboratory Standards Institute (CLSI) EP34, 1st ed.*
| mg/L | |
|---|---|
| Analytical Measuring Interval (AMI)ᵃ | 0.30–10.00 |
| Extended Measuring Interval (EMI)ᵇ | 10.00–40.00 |
| Reportable Intervalᶜ | 0.30–40.00 |
ᵃ AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ). This is determined by the range of values in mg/L that demonstrated acceptable performance for linearity, imprecision, and bias.
ᵇ EMI: The EMI extends from the ULoQ to the ULoQ × sample dilution.
ᶜ The reportable interval extends from the LoQ to the upper limit of the EMI.
*Clinical and Laboratory Standards Institute (CLSI). Establishing and Verifying an Extended Measuring Interval Through Specimen Dilution and Spiking. 1st ed. CLSI Guideline EP34. Wayne, PA: CLSI; 2018.
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Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
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B. Within-Laboratory Precision (20-Day)
A study was performed based on guidance from the CLSI document EP05-A3.* Testing was conducted using 1 lot of Cystatin C reagents, 1 lot of Cystatin C Calibrators, 1 lot of Cystatin C Controls, and 1 instrument. Two controls and 4 human serum panels were tested in a minimum of 2 replicates, twice per day on 20 days.
| Sample | n | Mean (mg/L) | Within-Run (Repeatability) | Within-Laboratoryᵃ |
|---|---|---|---|---|
| SD | %CV | |||
| Control Level 1 | 80 | 0.81 | 0.01 | 1.0 |
| Control Level 2 | 80 | 4.11 | 0.03 | 0.6 |
| Panel A (native) | 80 | 0.49 | 0.01 | 1.7 |
| Panel B (native) | 80 | 0.92 | 0.01 | 0.8 |
| Panel C (native) | 80 | 5.89 | 0.03 | 0.5 |
| Panel D (supplemented) | 80 | 8.95 | 0.07 | 0.8 |
ᵃ Within-Laboratory variability contains within-run, between-run, and between-day variance components.
*Clinical and Laboratory Standards Institute (CLSI). Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline—Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI;2014.
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Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
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C. Reproducibility
A study was performed based on guidance from the CLSI document EP05--A3.* Testing was conducted at each of 3 testing sites using 2 lots of the Cystatin C reagents, 1 lot of the Cystatin C Calibrators, 1 lot of the Cystatin C Controls, and 1 instrument. Two controls and 3 human serum panels were tested in a minimum of 4 replicates at 2 separate times per day on 5 different days.
| Sample | n | Mean (mg/L) | Repeatability | Within-Laboratoryᵃ | Between-Site | Between-Lot | Overall Reproducibilityᵇ |
|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | |||
| Control Level 1 | 240 | 0.81 | 0.01 | 1.5 | 0.02 | 2.0 | 0.00 |
| Control Level 2 | 240 | 4.08 | 0.02 | 0.6 | 0.04 | 0.9 | 0.02 |
| Panel 1 | 240 | 0.49 | 0.02 | 5.0 | 0.03 | 5.4 | 0.00 |
| Panel 2 | 240 | 0.93 | 0.01 | 1.3 | 0.01 | 1.6 | 0.00 |
| Panel 3 | 240 | 8.80 | 0.09 | 1.0 | 0.13 | 1.5 | 0.00 |
ᵃ Includes repeatability (within-run), between-run, and between-day variability.
ᵇ Includes repeatability (within-run), between-run, between-day, between-site, and between-lot variability.
*Clinical and Laboratory Standards Institute (CLSI). Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline—Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI;2014.
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Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 8 of 12
D. Accuracy
A study was performed to estimate the bias of the Cystatin C assay relative to standard reference material (ERM-DA471/IFCC). Testing was conducted using 2 lots of the Cystatin C reagents, 2 lots of the Cystatin C calibrators, and 1 instrument. The bias ranged from 1.3% to 1.8% across all reagent and calibrator lots.
E. Linearity
A study was performed based on guidance from the CLSI document EP06, 2nd ed.* This assay is linear across the AMI of 0.30 to 10.00 mg/L.
F. Lower Limits of Measurement
A study was performed based on guidance from the CLSI document EP17-A2.† Testing was conducted using 3 lots of the Cystatin C reagents on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.
| mg/L | |
|---|---|
| LoBᵃ | 0.03 |
| LoDᵇ | 0.05 |
| LoQᶜ | 0.30 |
ᵃ The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
ᵇ The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
ᶜ The LoQ is defined as the lowest concentration at which a total allowable error of 25% was met and was determined from n ≥ 60 replicates of low-analyte level samples.
*Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedures. 2nd ed. CLSI Guideline EP06. Wayne, PA: CLSI; 2020.
†Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline—Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
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Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 9 of 12
G. Analytical Specificity
1. Potentially Interfering Endogenous Substances
A study was performed based on guidance from the CLSI document EP07, 3rd ed.* Each substance was tested at 2 levels of the analyte (approximately 0.79 and 3.95 mg/L).
No significant interference (interference within ± 0.08 mg/L for samples < 0.79 mg/L) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Bilirubin (conjugated) | 60 mg/dL |
| Bilirubin (unconjugated) | 60 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Rheumatoid factor | 550 IU/mL |
| Total protein | 10.2 g/dL |
| Triglycerides | 1500 mg/dL |
No significant interference (interference within ± 10.0% for samples ≥ 0.79 mg/L) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Bilirubin (conjugated) | 60 mg/dL |
| Bilirubin (unconjugated) | 60 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Rheumatoid factor | 1200 IU/mL |
| Total protein | 11.8 g/dL |
| Triglycerides | 1500 mg/dL |
*Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
Page 14
SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 10 of 12
Interference beyond ± 0.08 mg/L for samples < 0.79 mg/L and beyond ± 10.0% for samples ≥ 0.79 mg/L (based on 95% Confidence Interval [CI]) was observed at the concentrations shown below for the following substances.
| Potentially Interfering Substance | Interferent Level | Analyte Level | % Interference (95% CI) |
|---|---|---|---|
| Rheumatoid factor | 1200 IU/mL | 0.79 mg/L | 0.19 (0.16, 0.22) |
| Total protein | 15 g/dL | 0.79 mg/L | 0.27 (0.26, 0.28) |
| Total protein | 15 g/dL | 3.95 mg/L | 18.5% (18.0%, 18.9%) |
2. Potentially Interfering Exogenous Substances
A study was performed based on guidance from the CLSI document EP07, 3rd ed.* Each substance was tested at 2 levels of the analyte (approximately 0.79 and 3.95 mg/L).
No significant interference (interference within ± 0.08 mg/L for samples < 0.79 mg/L and within ± 10.0% for samples ≥ 0.79 mg/L) was observed at the following concentrations.
| Potentially Interfering Drug | Interferent Level | Potentially Interfering Drug | Interferent Level |
|---|---|---|---|
| Acetaminophen | 250 mg/L | Doxycycline | 50 mg/L |
| Acetylcysteine | 150 mg/L | Ibuprofen | 500 mg/L |
| Acetylsalicylic acid | 1000 mg/L | Levodopa | 20 mg/L |
| Ampicillin-Na | 1000 mg/L | Methyldopa | 22.5 mg/L |
| Ascorbic acid | 300 mg/L | Metronidazole | 200 mg/L |
| Biotin | 3510 ng/mL | Phenylbutazone | 400 mg/L |
| Ca-dobesilate | 200 mg/L | Rifampicin | 60 mg/L |
| Cefoxitin | 6600 mg/L | Sodium heparin | 10 U/mL |
| Cyclosporin | 5 mg/L | Theophylline (1,3-dimethylxanthine) | 100 mg/L |
*Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
Page 15
SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 11 of 12
H. Method Comparison
A study was performed based on guidance from the CLSI document EP09c, 3rd ed.* using the Passing-Bablok regression method.
Cystatin C on Alinity c vs a Comparator Cystatin C assay
| n | Units | Correlation Coefficient | Intercept | Slope | Concentration Range | |
|---|---|---|---|---|---|---|
| Serum | 161 | mg/L | 1.00 | -0.07 | 1.03 | 0.60–8.20 |
I. Matrix Comparison (Tube Type Equivalence)
A study was performed to evaluate the suitability of specific blood collection tube types for use with the Cystatin C assay. The following blood collection tube types were determined to be acceptable for use with the Cystatin C assay:
Serum
- Serum
- Serum separator
Plasma
- Dipotassium EDTA
- Lithium heparin
- Lithium heparin separator
- Sodium heparin
- Tripotassium EDTA
J. High Dose Hook
There is no prozone interference for undiluted samples containing up to 40.00 mg/L of cystatin C.
*Clinical and Laboratory Standards Institute (CLSI). Measurement Procedure Comparison and Bias Estimation Using Patient Samples. 3rd ed. CLSI Guideline EP09c. Wayne, PA: CLSI; 2018.
Page 16
SENTINEL CH. SpA
Assay Name: Cystatin C
Traditional 510(k)
Administrative Documentation – 510(k) Summary
Page 12 of 12
K. Expected Values (Reference Interval)
A study was performed based on guidance from CLSI EP28-A3c.* Testing was conducted on apparently healthy individuals, including 105 females and 145 males, with an estimated glomerular filtration rate (eGFR) > 80 (mL/min/1.73 m²). The age of the study population ranged from 18 to 69 years.
The reference range using the 2.5th and 97.5th percentile is summarized below.
| Range (mg/L) | |
|---|---|
| Adult | 0.59–1.28 |
IX. Summary of Clinical Performance
This section does not apply.
X. Conclusion
The information presented in this 510(k) premarket notification demonstrate that the performance of the subject device, Cystatin C for use with Alinity c system (List Number 06T32), is substantially equivalent to the predicate device, Tina-quant Cystatin C Gen.2 (K161817).
The minor differences between predicated device and candidate device raise no new issues of safety and effectiveness and do not impact the indications for use or technological characteristics.
*Clinical and Laboratory Standards Institute (CLSI). Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline—Third Edition. CLSI document EP28-A3c. Wayne, PA: CLSI; 2008.
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.