(71 days)
The Nichols Advantage® Chemiluminescence Ferritin Immunoassay is designed for use with the Nichols Advantage® Specialty System for the quantitative determination of ferritin in human serum or plasma. This assay is intended to aid in the diagnosis of iron deficiency anemia and iron overload.
The Nichols Advantage® Ferritin Assay is a two-site chcmiluminescence assay for use with the Nichols Advantage® Specialty System
Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate section with pass/fail thresholds. Instead, it presents the device's performance characteristics and compares them to a predicate device. I've extracted the performance data for the Nichols Advantage® Ferritin device.
| Performance Characteristic | Nichols Advantage® Ferritin Reported Performance |
|---|---|
| Intra-Assay | |
| Mean 16 ng/mL | 4.6 %CV |
| Mean 48 ng/mL | 3.9 %CV |
| Mean 159 ng/mL | 4.4 %CV |
| Mean 437 ng/mL | 4.9 %CV |
| Inter-Assay | |
| Mean 19 ng/mL | 12.2 %CV |
| Mean 47 ng/mL | 7.2 %CV |
| Mean 153 ng/mL | 6.3 %CV |
| Mean 372 ng/mL | 5.9 %CV |
| Recovery | 94 - 104 % |
| Parallelism | 99 - 114 % |
| High Dose Hook Effect | Greater than 16,000 ng/mL |
| Specificity | 100% (Spleen Ferritin) |
| Cross-Reactivity | 100% (Liver Ferritin) |
| Method Comparison | |
| Range of Results | 2.3 ng/mL to 608 ng/mL |
| Linear Regression Equation | y = 0.94x - 4.7 ng/mL |
| Correlation Coefficient (r) | 0.98 |
Implicit Acceptance Criteria: The acceptance criteria for this type of submission (510(k)) are implicitly that the new device performs "substantially equivalently" to the predicate device. While specific thresholds are not listed, the comparable performance across these metrics is intended to demonstrate that the new device is as safe and effective as the predicate.
Study Proving Acceptance Criteria:
The document describes several studies conducted to characterize the performance of the Nichols Advantage® Chemiluminescence Ferritin Immunoassay.
2. Sample Size Used for the Test Set and Data Provenance
- Intra-Assay:
- For each of the four mean concentration levels, 20 samples (n=20) were used.
- Inter-Assay:
- For each of the four mean concentration levels, 20 samples (n=20) were used.
- Method Comparison:
- The document states "Range of Results: 2.3 ng/mL to 608 ng/mL" and provides a correlation coefficient. However, the exact number of samples used for this particular method comparison study is not explicitly stated.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay device does not typically rely on "expert consensus" or "radiologist interpretation" for establishing ground truth in the same way imaging devices do. The ground truth for performance characteristics like precision, recovery, and linearity is established through:
- Reference materials/standards: Precision studies (intra-assay, inter-assay) use samples with known or established concentrations.
- Known spikes/dilutions: Recovery and parallelism studies involve adding known amounts of analyte or diluting samples, where the expected values serve as the ground truth.
- Comparison to a well-established method: The method comparison study uses a predicate device (Chiron Diagnostics ACS:180® Ferritin +C Assay) as a reference, where the results from the predicate device serve as a comparator for the 'truth' measure.
Therefore, the concept of "experts establishing ground truth" in the diagnostic imaging sense is not applicable here.
4. Adjudication Method for the Test Set
Not applicable. The types of studies described (e.g., precision, recovery, method comparison) do not involve subjective interpretation or a need for adjudication methods like 2+1 or 3+1. The results are quantitative measurements.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with/without AI
Not applicable. This is an in-vitro diagnostic (IVD) device (a laboratory test) and not an AI-powered imaging or diagnostic interpretation system that involves human readers. Therefore, an MRMC study or the concept of human readers improving with/without AI assistance is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described reflect the standalone performance of the Nichols Advantage® Chemiluminescence Ferritin Immunoassay. It's a fully automated system (the Nichols Advantage® Specialty System) that quantifies ferritin levels, and the performance characteristics reported are those of the device itself, without human interpretation playing a direct role in the measurement process.
7. The Type of Ground Truth Used
The ground truths used for the various performance characteristics are:
- Precision (Intra-Assay, Inter-Assay): Established concentrations of control materials or pooled patient samples.
- Recovery & Parallelism: Expected values based on known additions (spikes) or dilutions of samples.
- High Dose Hook Effect: The presence or absence of a hook effect at extremely high concentrations is determined by observing the assay's response to spiked samples.
- Specificity and Cross-Reactivity: Known concentrations of ferritin from different sources (spleen, liver) or potential interfering substances are used to assess the assay's accuracy in identifying only the target analyte.
- Method Comparison: The results obtained from the established, legally marketed predicate device (Chiron Diagnostics ACS:180® Ferritin +C Assay) serve as the comparative ground truth.
8. The Sample Size for the Training Set
The document does not provide information about a "training set" or its sample size. For an IVD device like this, the development typically involves calibration, reagent optimization, and performance verification. There isn't an explicit "training set" in the machine learning sense. The performance characteristics described are typically part of a validation or verification study, not a distinct training phase.
9. How the Ground Truth for the Training Set Was Established
Since no training set is mentioned in the machine learning context, this question is not applicable based on the provided text. The calibration and optimization of such assays would generally involve using characterized reference materials and calibrators, for which concentrations are established through methods traceable to international standards or established physicochemical techniques.
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FEB 2 1999
Nichols Institute Diagnostics Nichols Advantage® Ferritin 510(k) Notification
11.0 510(k) SUMMARY
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| 510(k) Number: | not known | K984186 |
|---|---|---|
| ---------------- | ----------- | --------- |
1. Name of Submitter, Contact Person and Date Summary Prepared:
Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, CA 92675-4703 Phone: 949-240-5260 Fax: 949-240-5313
Contact Person: Jimmy Wong Date Prepared: November 20, 1998
2. Device Name
| Trade/Proprietary Name: | Nichols Advantage® Chemiluminescence FerritinImmunoassay |
|---|---|
| Common/Usual Name: | Ferritin Assay |
| Classification Name: | Ferritin Immunological Test System |
3. Predicate Device:
We claim substantial equivalence to the Chiron Diagnostics ACS:/80° Automated. We claim substantial +C Assay (K905770, Cleared March 12, 1991).
4. Device Description:
The Nichols Advantage® Ferritin Assay is a two-site chcmiluminescence assay for use with the Nichols Advantage® Specialty System
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5. Intended Use
The Nichols Advantage® Chcmiluminescence Ferritin Immunoassay is intended for use on the Nichols Advantage® Specialty System for the quantitative determination of ferritin in human serum or plasma.
6. Comparison to predicate device:
The Nichols Advantage® Ferritin Assay is substantially equivalent to other products in commercial distribution for similar use. Most notably, it is substantially equivalent to the Chiron Diagnostics ACS:180 Ferritin Immunoassay.
The following tables compare the Nichols Advantage Ferritin Assay with the predicate device, Chiron Diagnostics ACS:180 Ferritin Immunoassay .
Similarities:
- Intended Use: For the quantitative determination of ferritin in human serum or plasma ● (Nichols Advantage Ferritin Assay); in serum (Chiron Diagnostics ACS:180 Ferritin Immunoassay).
- Both assays use specific antibodies to bind ferritin. ●
- Both assays use human serum for the test sample. ●
- Both assays use chemiluminometric technology based on acridinium esters. .
- The sensitivity of both assays is sufficient to measure ferritin levels found in normal, . iron deficient and iron overload patients.
| Feature | Nichols Advantage®Ferritin | ACS:180® AutomatedChemiluminescenceSystem Ferritin +CAssay |
|---|---|---|
| Sample Size | 150 microliters | 25 microliters |
| Calibration | Two point calibration every twoweeks (maximum) of storedworking calibration curve; orwhen controls out of range. | Two point calibration every15 days of stored workingcalibration curve; or whencontrols out of range. |
| Solid Phase | Streptavidin-coated magneticparticles. Streptavidin-biotinseparation technology. | Mouse monoclonal anti-ferritinantibodies covalently coupledto paramagnetic particles.Antibody sandwich-formationseparation technology. |
| Incubation | 30 minutes at 37°C | 7.5 minutes at 37°C |
| Sensitivity | 2 ng/mL in serum or plasma | 0.5 ng/mL in serum |
Differences:
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Nichols Institute Diagnostics
Nichols Advantage® Ferritin 510(k) Notification
Performance Characteristics:
.
..............................................................................................................................................................................
| FEATURE | Nichols Advantage®Chemiluminescence Ferritin | Chiron Diagnostics ACS:180®Ferritin +C Assay | ||||
|---|---|---|---|---|---|---|
| Intra-Assay | Mean(ng/mL) | n | %CV | Mean(ng/mL) | n | %CV |
| 16 | 20 | 4.6 | 13 | 24 | 2.8 | |
| 48 | 20 | 3.9 | 55 | 24 | 2.8 | |
| 159 | 20 | 4.4 | 163 | 24 | 2.7 | |
| 437 | 20 | 4.9 | 360 | 24 | 3.6 | |
| Inter-Assay | Mean(ng/mL) | n | %CV | Mean(ng/mL) | n | %CV |
| 19 | 20 | 12.2 | 13 | 8 | 5.0 | |
| 47 | 20 | 7.2 | 55 | 8 | 6.1 | |
| 153 | 20 | 6.3 | 163 | 8 | 4.9 | |
| 372 | 20 | 5.9 | 360 | 8 | 5.1 | |
| Recovery | 94 - 104 | 93 - 112 | ||||
| Parallelism | 99 - 114 | 92 - 112 | ||||
| High Dose Hook Effect | Greater than 16,000 ng/mL | 80,000 ng/mL | ||||
| Specificity andCross-Reactivity: | ||||||
| Spleen Ferritin | 100% | Not Determined | ||||
| Liver Ferritin | 100% | 106% | ||||
| Method Comparison | ||||||
| Range of Results | 2.3 ng/mL to 608 ng/mL | 7.0 ng/mL to 663 ng/mL | ||||
| Linear Regression Equation | $y = 0.94x - 4.7 ng/mL$ | |||||
| Correlation Coefficient (r) | 0.98 | |||||
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2 1999 FEB
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Jimmy Wong Manager, Clinical and Technical Affairs NICHOLS INSTITUTE DIAGNOSTICS 33051 Calle Aviador San Juan Capistrano, CA 92675-4703
Re: K984186 Trade Name: Nichols Advantage® Chemiluminescence Ferritin Immunoassay Regulatory Class: II Product Code: DBF November 20, 1998 Dated: November 23, 1998 Received:
Dear Mr. Wong:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). You may, therefore, market the device, subject to the general controls The general controls provisions of the provisions of the Act. 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 either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. this response to your premarket notification Please note: submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 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 Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Putman
Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
510(k) Number (if known): K984186
Device Name: Nichols Advantage® Chemiluminescence Ferritin Immunoassay
Indications For Use:
The Nichols Advantage® Chemiluminescence Ferritin Immunoassay is designed for use with the Nichols Advantage® Specialty System for the quantitative determination of ferritin in human serum or plasma. This assay is intended to aid in the diagnosis of iron deficiency anemia and iron overload.
Peter E. Mayeri
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use レ (Per 21 CFR 801.109) OR
Over-The-Counter Use (Optional Format 1-2-96)
§ 866.5340 Ferritin immunological test system.
(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).