(275 days)
Immunoturbidimetric assay for the quantitative in vitro determination of ceruloplasmin in human serum and plasma on Roche automated clinical chemistry analyzers. Measurements obtained by this device aid in the diagnosis of copper metabolism disorders.
The Tina-quant Ceruloplasmin assay employs an immunoturbidimetric test in which anti-ceruloplasmin antibodies react with antigen in the sample to form antigen/antibody complexes which, following agglutination can be determined turbidimetrically.
Here's a breakdown of the acceptance criteria and study information for the Tina-quant Ceruloplasmin Assay, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criterion | Criteria Value / Threshold | Reported Device Performance | Study Type to Demonstrate Performance (Implicit) |
|---|---|---|---|---|
| Precision (Repeatability) | Control Low | SD ≤ 0.4 mg/dL; CV ≤ 1.5% | SD 0.4 mg/dL; CV 1.5% | Internal Verification |
| Control High | SD ≤ 0.9 mg/dL; CV ≤ 0.9% | SD 0.9 mg/dL; CV 0.9% | Internal Verification | |
| Serum Low | SD ≤ 1.2 mg/dL, CV ≤ 1.2% | SD 1.2 mg/dL, CV 1.2% | Internal Verification | |
| Serum Medium | SD ≤ 0.5 mg/dL, CV ≤ 0.8% | SD 0.5 mg/dL, CV 0.8% | Internal Verification | |
| Serum High | SD ≤ 0.9 mg/dL, CV ≤ 0.8% | SD 0.9 mg/dL, CV 0.8% | Internal Verification | |
| Precision (Intermediate/Total) | Control Low | SD ≤ 0.4 mg/dL; CV ≤ 1.6% | SD 0.4 mg/dL; CV 1.6% | Internal Verification |
| Control High | SD ≤ 0.7 mg/dL; CV ≤ 1.1% | SD 0.7 mg/dL; CV 1.1% | Internal Verification | |
| Serum Low | SD ≤ 0.4 mg/dL, CV ≤ 1.6% | SD 0.4 mg/dL, CV 1.6% | Internal Verification | |
| Serum Medium | SD ≤ 0.7 mg/dL, CV ≤ 1.0% | SD 0.7 mg/dL, CV 1.0% | Internal Verification | |
| Serum High | SD ≤ 1.1 mg/dL, CV ≤ 0.9% | SD 1.1 mg/dL, CV 0.9% | Internal Verification | |
| Analytical Sensitivity | Limit of Blank (LoB) | ≤ 2 mg/dL | ≤ 2 mg/dL | Internal Verification |
| Limit of Detection (LoD) | ≤ 3 mg/dL | ≤ 3 mg/dL | Internal Verification | |
| Analytical Specificity | Interference (Common Drugs) | No interference at common therapeutic concentrations | No interference was found at common therapeutic concentrations using common drug panels. | Interference Study |
| Interferences (Recovery) | Icterus | Recovery within ±10% up to I-index 60 | No significant interference up to an I index of 60 (approx. 60 mg/dL conjugated/unconjugated bilirubin) | Interference Study |
| Hemolysis | Recovery within ±10% up to H-index 350 | No significant interference up to an H index of 350 (approx. 350 mg/dL hemoglobin) | Interference Study | |
| Lipemia | Recovery within ±10% up to L-index 400 | No significant interference up to an L Index of 400 mg/dL. | Interference Study | |
| Rheumatoid Factor (RF) | No interference up to RF < 76 IU/mL (highest tested) | Rheumatoid factors <76 IU/mL do not interfere. | Interference Study | |
| High-Dose Hook Effect | No Hook Effect | Up to 500 mg/dL ceruloplasmin | No high-dose hook effect was found up to ceruloplasmin concentrations of 500 mg/dL. | Internal Verification |
| Method Comparison | Correlation with predicate device | y = 1.02x + 0.302 (Passing Bablock); $\tau$ = 0.934 y = 0.980x - 0.411 (Linear Regression); r = 0.997 | Passing Bablock: y = 1.02x + .302; $\tau$ = 0.934 Linear Regression: y = 0.980x - 0.411; r = 0.997 | Method Comparison Study |
Study Information
Here's the detailed study information based on the provided text, recognizing that this is a 510(k) summary for an in vitro diagnostic (IVD) assay, which typically focuses on analytical performance rather than clinical endpoints or interpretation by human readers.
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Sample size used for the test set and the data provenance:
- Precision Studies (Repeatability and Intermediate Precision):
- Test set size: Not explicitly stated as a single "test set" size. The data for precision studies are typically derived from replicate measurements of control materials and human serum samples. The text lists values for "Control Low," "Control High," "Serum Low," "Serum Medium," and "Serum High." The number of replicates or days over which these were run is not detailed in the provided summary.
- Data provenance: Not specified, but generally, analytical validation studies for IVDs use samples from various sources to ensure broad applicability. Likely internal lab data.
- Analytical Sensitivity (LoB, LoD):
- Test set size: Not specified. These are determined through statistical methods based on multiple measurements of blank samples and low-level analyte samples.
- Data provenance: Not specified. Likely internal lab data.
- Analytical Specificity/Interferences:
- Test set size: Not specified for each interference substance, but implies various concentrations of bilirubin, hemoglobin, intralipid, and rheumatoid factor were tested.
- Data provenance: Not specified. Likely internal lab data and commercially available panels.
- Method Comparison Study:
- Test set size: n = 82 samples.
- Data provenance: Not specified (e.g., country of origin). The study involved "samples concentrations were between 13.2 and 132.1 mg/dL," suggesting human serum/plasma samples. It's a retrospective comparison against the predicate device.
- Precision Studies (Repeatability and Intermediate Precision):
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is not applicable to this type of device and study. The "ground truth" for an IVD diagnostic assay's analytical performance is the true concentration of the analyte (ceruloplasmin) in a sample, determined by a reference method or known concentration in control materials. It does not involve expert interpretation or consensus.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- This question is not applicable to this type of device and study. Adjudication methods are relevant for studies involving human interpretation (e.g., imaging studies) where disagreements among readers need resolution. For an analytical assay, the "result" is a quantitative value.
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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:
- This question is not applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that aids human readers. The study compares the new assay's performance to a predicate device, not human performance with/without AI.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The Tina-quant Ceruloplasmin Assay is a fully automated immunoturbidimetric assay on Roche automated clinical chemistry analyzers. Its performance is measured independently of human interpretation of the assay result. Humans operate the analyzer and interpret the quantitative output in a clinical context, but the assay itself is standalone in generating the ceruloplasmin concentration.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For precision and analytical sensitivity/specificity, the "ground truth" generally refers to:
- Known concentrations in control materials: For controls with assigned ceruloplasmin values.
- Reference measurement procedures: For spiked samples or characterized serum pools where the true ceruloplasmin concentration is established by a highly accurate method.
- For interferences, the ground truth is the expected recovery of ceruloplasmin in the presence of interferents, with the baseline ceruloplasmin value serving as the reference.
- For the method comparison study, the "ground truth" for evaluating the new device's accuracy is the results obtained from the predicate device (Roche Ceruloplasmin assay on cobas c510). This is a common approach for demonstrating substantial equivalence for IVDs.
- For precision and analytical sensitivity/specificity, the "ground truth" generally refers to:
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The sample size for the training set:
- This information is not provided in the 510(k) summary. For an immunoturbidimetric assay like this, there isn't a "training set" in the sense of machine learning. The assay's parameters (e.g., reagent concentrations, reaction times) are developed and optimized internally by the manufacturer through R&D, not through an explicit "training set" of patient data.
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How the ground truth for the training set was established:
- Since there isn't a "training set" in the machine learning sense, this question is not applicable. The underlying method for establishing the analytical accuracy of instruments or assays relies on reference materials and reference methods. The device is standardized against the reference preparation CRM 470 (RPPHS - Reference Preparation for Proteins in Human Serum), which serves as a fundamental aspect of establishing accuracy and traceability.
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Tina-quant Ceruloplasmin Assay
510(k) Summary MAR } 8 2010 According to the requirements of 21 CFR 807.92, the following information Introduction provides sufficient detail to understand the basis for a determination of substantial equivalence. Submitter . Roche Diagnostics name, address, 9115 Hague Road contact Indianapolis, IN 46250 (317) 521 - 3723 Contact Person: Kathie J. Goodwin Date Prepared: June 10, 2009 Device Name Proprietary names: Tina-Quant Ceruloplasmin Common names: Ceruloplasmin assay Classification names: Ceruloplasmin Immunological Test System Product codes: CHN The Tina-quant Ceruloplasmin assay employs an immunoturbidimetric test in Device Description which anti-ceruloplasmin antibodies react with antigen in the sample to form antigen/antibody complexes which, following agglutination can be determined turbidimetrically. and the manager of the comments of the comments of the comments of Intended use Immunoturbidimetric assay for the quantitative in vitro determination of ceruloplasmin in human serum and plasma on Roche automated clinical chemistry analyzers. Measurements obtained by this device aid in the diagnosis of copper Indications for Use metabolism disorders. The Tina-quant Ceruloplasmin assay is substantially equivalent to the Roche Substantial equivalence Ceruloplasmin assay on the cobas c501 analyzer. The cobas c501 Ceruloplasmin assay was cleared under K062114.
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Tina-quant Ceruloplasmin Assay
510(k) Summary, Continued
Substantial
equivalence –
comparison
| Feature | Tina-quant Ceruloplasmin Assay | Predicate Device: cobas c501Ceruloplasmin Assay (K062114) |
|---|---|---|
| Intended Use | Immunoturbidimetric assay for thequantitative in vitro determination ofceruloplasmin in human serum andplasma on Roche automated clinicalchemistry analyzers. | Immunoturbidimetric assay for thequantitative in vitro determination ofceruloplasmin in human serum andplasma on Roche/Hitachi cobas csystems. |
| Indication for Use | Measurements obtained by this deviceaid in the diagnosis of coppermetabolism disorders. | Same |
| Assay Protocol | Immunoturbidimetric | Same |
| Sample Type | Serum and Li-heparin Plasma | Same |
| Labeled Instrument Platform | Roche/Hitachi analyzers | Roche Hitachi cobas c systems |
| Calibrator | C.f.a.s. PAC | Same |
| Calibration frequency | Full calibration is recommended afterreagent lot change and as requiredfollowing quality control procedures. | Same |
| Controls | Commercially available control | Same |
| Traceability | Standardized against the referencepreparation CRM 470 (RPPHS -Reference Preparation for Proteins inHuman Serum) | Same |
| Reagent Stability | 3 days at 2-8 Deg. C4 weeks at (-15)-(-25) Deg. C | Same |
| Measuring Range | 3-140 mg/dL | Same |
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| Precision | Repeatability (Within-run) | Within-run |
|---|---|---|
| Control Low: SD 0.4 mg/dL; CV 1.5% Control High: SD 0.9 mg/dL; CV 0.9% Serum Low: SD 1.2 mg/dL, CV 1.2% Serum Medium: SD 0.5 mg/dL, CV 0.8% Serum High: SD 0.9 mg/dL, CV 0.8% | Precinorm Protein: SD 0.2 mg/dL; CV 0.6% Precipath Protein: SD 0.2 mg/dL; CV 0.6% Human Serum 1: 0.3 mg/dL, CV 1.5% Human serum 2: 0.3 mg/dL, CV 0.8% | |
| Intermediate Precision (Total) Control Low: SD 0.4 mg/dL; CV 1.6% Control High: SD 0.7 mg/dL; CV 1.1% Serum Low: SD 0.4 mg/dL, CV 1.6% Serum Medium: SD 0.7 mg/dL, CV 1.0% Serum High: SD 1.1 mg/dL, CV 0.9% | Total Precinorm Protein: SD 0.4, CV 1.4% Precipath Protein: SD 0.4, CV 1.0% Human Serum 3: SD 0.5, CV 2.6% Human Serum 4: SD 0.7, CV 1.5% | |
| AnalyticalSensitivity | Limit of Blank (LoB) $≤$ 2 mg/dLLimit of Detection (LoD) $≤$ 3 mg/dL | Lower Detection Limit = 3 mg/dL |
| AnalyticalSpecificity | No interference was found at commontherapeutic concentrations usingcommon drug panels. | Same |
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| Interferences | Criterion: Recovery within ± 10% of initial value. | Criterion: Same |
|---|---|---|
| Icterus: no significant interference up to an I index of 60 (approximate conjugated and unconjugated bilirubin concentration: 60 mg/dL) | Icterus: Same | |
| Hemolysis: No significant interference up to an H index of 350 (approximate hemoglobin concentration: 350 mg/dL) | Hemolysis: Same | |
| Lipemia No significant interference up to an L Index of 400 mg/dL. | Lipemia (Intralipid): No significant interference up to an L index of 200. There is poor correlation between the L index (corresponds to turbidity) and triglyceride concentration. | |
| Rheumatoid Factor: Rheumatoid factors <76 IU/mL do not interfere. (Highest concentration tested) | RF: Rheumatoid factors up to 100 IU/mL do not interfere. | |
| No high-dose hook effect was found up to ceruloplasmin concentrations of 500 mg/dL. | High-dose hook effect: Same | |
| In very rare cases, gammopathy, in particular type IgM (Waldenstrom's macroglobulinemia), may cause unreliable results. | Same | |
| Expected Values | Male: 15-30 mg/dLFemale: 16-45 mg/dL | 20.0 - 60.0 mg/dL |
| MethodComparison | A comparison of the Roche Tina-quant Ceruloplasmin assay (x) with the Roche Ceruloplasmin assay on cobas c510 (y) gave the following correlation (mg/dL) :Passing Bablocky = 1.02x + .302$\tau$ = 0.934Linear Regressiony = 0.980x - 0.411r = 0.997n = 82Samples concentrations were between 13.2 and 132.1 mg/dL | |
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Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
Roche Diagnostics c/o Ms. Kathie Goodwin, MBA, MT (ASCP)BB, RAC Regulatory Affairs Consultant 9115 Hague Road, PO Box 50416 Indianapolis, IN 46250-0416
MAR 1 8 2010
Re: K091741
Trade/Device Name: Tina-Quant Ceruloplasmin Regulation Number: 21 CFR & 866.5210 Regulation Name: Ceruloplasmin Immunological Test System Regulatory Class: Class II Product Code: CHN Dated: March 2, 2010 Received: March 10, 2010
Dear Ms. Goodwin:
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. 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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); medical device reporting (reporting of
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Page 2 – Ms. Kathie Goodwin
medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
in char
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known):
Device Name: Roche/Hitachi Tina-Quant Ceruloplasmin
Indication For Use:
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche automated clinical chemistry analyzers.
Prescription Use XXXX (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Beena Philip
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K091741
§ 866.5210 Ceruloplasmin immunological test system.
(a)
Identification. A ceruloplasmin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ceruloplasmin (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin aid in the diagnosis of copper metabolism disorders.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.