(35 days)
The IRON method for the Dimension® clinical chemistry system is an in vitro diagnostic test intended to quantitatively measure iron in human serum and plasma. Iron measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia and other disorders of iron metabolism.
The Dimension® IRON Flex® reagent cartridge (DF85) is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight well cartridge for use on the Dade Behring Dimension® clinical chemistry system for the quantitative determination of iron in serum and plasma.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
| Performance Characteristic | Acceptance Criteria (Implied/Direct) | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | Based on CLSI/NCCLS EP5-A2 guideline. Specific CV% targets are implied by showing results within acceptable clinical ranges. | Repeatability (%CV): Plasma pool: 0.5% Serum pool 1: 0.5% Serum pool 2: 0.5% Serum pool 3: 0.5% BioRad Lyphochek® control Level 1: 0.5% BioRad Lyphochek® control Level 2: 1.1% BioRad Lyphochek® Anemia control Level 1: 1.3% Reduced Sample Volume Serum pool 1: 0.6% Reduced Sample Volume Serum pool 2: 0.5% Reduced Sample Volume Serum pool 3: 0.5% Reduced Sample Volume BioRad Lyphochek® Anemia control Level 1: 1.3% Reduced Sample Volume BioRad Multiqual® control Level 3: 0.7% Within-lab Standard Deviation (%CV): Plasma pool: 0.7% Serum pool 1: 0.6% Serum pool 2: 1.1% Serum pool 3: 0.8% BioRad Lyphochek® control Level 1: 0.7% BioRad Lyphochek® control Level 2: 1.9% BioRad Lyphochek® Anemia control Level 1: 1.9% Reduced Sample Volume Serum pool 1: 0.9% Reduced Sample Volume Serum pool 2: 1.1% Reduced Sample Volume Serum pool 3: 0.8% Reduced Sample Volume BioRad Lyphochek® Anemia control Level 1: 1.9% Reduced Sample Volume BioRad Multiqual® control Level 3: 0.9% |
| Linearity/Assay Reportable Range | Correlation coefficient of 0.999, slope of 0.999, and intercept of 0.178. Assay range claim: 5.0 µg/dL to 1000 µg/dL. | Correlation Coefficient: 0.999 Slope: 0.999 Intercept: 0.178 Assay Range Claim: 5.0 µg/dL to 1000 µg/dL |
| Detection Limit (Analytical Sensitivity) | Ability to distinguish iron from zero. | Analytical Sensitivity: 5 µg/dL [0.9 µmol/L] |
| Analytical Specificity (Interference) | Systematic inaccuracies (bias) due to interfering substances < 10% within specified iron concentrations. | Inaccuracies < 10% at iron concentrations of 26-38 µg/dL and 118-136 µg/dL for tested substances. (Specific interfering substances and non-interfering substances are in the package insert, not detailed here.) |
| Method Comparison (vs. Predicate Device) | Linear regression relationship with predicate device (Dimension® IRN (DF49A)) indicating strong correlation. (Implied acceptability based on similarity to predicate) | Slope: 0.980 Intercept: -0.488 µg/dL Correlation Coefficient: 0.9996 Range of IRON values in study: 9 to 963 µg/dL |
| Matrix Comparison | Excellent agreement between serum, lithium heparin plasma, and sodium heparin plasma specimens; no clinically significant difference. | Sodium heparin plasma vs. serum: y = 0.988x + 0.804, r = 0.999 Lithium heparin plasma vs. serum: y = 0.985x + 1.42, r = 0.999 Lithium heparin plasma vs. sodium heparin plasma: y = 0.997x + 0.666, r = 0.999 |
| Traceability | Standardization to NIST SRM 937 Iron Metal Clinical Standard. | The Dimension® IRON Calibrator is standardized to NIST SRM 937. |
Study Details:
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Sample sizes used for the test set and the data provenance:
- Precision/Reproducibility: Not explicitly stated as "test set," but specimens (commercial controls, serum, and plasma pools) were analyzed in duplicate twice a day for 20 days.
- Linearity: Solutions of NIST SRM 937 were prepared by sequential mixing. The exact number of samples is not given, but they ranged from 0 to 2000 µg/dL iron.
- Analytical Specificity: Not explicitly stated, but interference testing was performed according to CLSI/NCCLS Protocol EP-7A.
- Method Comparison: 147 samples (99 individual patient serum samples + 48 individual patient serum samples spiked with NIST-937 reference iron material).
- Matrix Comparison: 129 matched specimens of serum and heparinized plasma.
- Data Provenance: Not explicitly stated, but given the nature of the device (in vitro diagnostic for human serum/plasma) and the use of patient samples, the data is prospective clinical data from a medical setting. The location (country of origin) is not specified.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This is an in vitro diagnostic device for quantitative iron measurement, where "ground truth" is established through analytical reference methods or reference materials (like NIST SRM 937) rather than expert interpretation of images or clinical cases.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable as the "test set" involves quantitative measurements on biological samples/controls against known values or reference methods, not subjective interpretation requiring adjudication.
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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:
- Not applicable. This is an IVD device for automated quantitative measurement, not an AI-assisted diagnostic imaging or interpretation system involving human readers.
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If a standalone (i.e., algorithm only without human-in-the loop performance) was done:
- Yes, the performance characteristics described (precision, linearity, detection limit, analytical specificity, method comparison, matrix comparison) represent the standalone performance of the Dimension® IRON Flex® reagent cartridge on the Dimension® clinical chemistry system, without human "in-the-loop" interpretation beyond standard laboratory procedures.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Reference Materials/Reference Methods:
- Linearity/Traceability: NIST SRM 937 Iron Metal Clinical Standard.
- Method Comparison: The predicate device, Dimension® IRN (DF49A), serves as the comparator, with its own established performance likely tracing back to similar reference methods/materials.
- Detection Limit: Based on statistical calculation (mean + 2 standard deviations) of a low-level calibrator.
- Reference Materials/Reference Methods:
-
The sample size for the training set:
- Not applicable/Not explicitly stated in the context of "training set" as it would be understood for an AI/machine learning model. For this type of IVD, the development process involves extensive R&D, formulation, and iterative testing, but not a distinct "training set" in the AI sense. The performance studies mentioned (precision, linearity, etc.) serve to validate the final reagent formulation and instrument integration.
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How the ground truth for the training set was established:
- Not applicable, as there isn't a "training set" in the context of an AI/ML device. The ground truth for the validation studies mentioned (e.g., linearity, method comparison) relies on established analytical standards and reference methods as described in point 6.
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MAR 8 2006
510(k) Summary for the Dimension® IRON Flex® reagent cartridge (DF85)
A. 510(k) Number: K060264
B. Analyte: Total iron
C. Type of Test: Quantitative
D. Applicant:
Dade Behring Inc., P.O. Box 6101, Newark, DE 19714-6101 Contact: Andrea M. Tasker, Regulatory Affairs and Compliance Manager (302) 631-9454
Date of Preparation: January 30, 2006
E. Proprietary and Established Names:
Dimension® Iron Flex® reagent cartridge (IRON-DF85)
F. Regulatory Information:
- Regulation section: 21 CFR §862.1410 Iron (non-heme) test system 1.
- Classification: Class I 2.
- Product Code: JIY 3.
- Panel: Chemistry (75) 4.
G. Intended Use:
l. Intended for Use:
The IRON method for the Dimension® clinical chemistry system is an in vitro diagnostic test intended to quantitatively measure iron in human serum and plasma.
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Indications for Use: The IRON method for the Dimension® clinical chemistry system is an in vitro diagnostic test intended to quantitatively measure iron in human serum and plasma. Iron measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia and other disorders of iron metabolism.
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Special condition for use statement(s): none
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- Special instrument Requirements: Dimension® clinical chemistry system
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H. Device Description:
The Dimension® IRON Flex® reagent cartridge (DF85) is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight well cartridge for use on the Dade Behring Dimension® clinical chemistry system for the quantitative determination of iron in serum and plasma.
I. Substantial Equivalence Information:
- Predicate Device: Dimension® IRN Iron Flex® reagent cartridge (DF49A)
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- Predicate K Number(s): K944093
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- Comparison with Predicate:
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| Intended Use | Quantitative determination oftotal iron | same |
| Reagentcomponents | Ferene® (chromophore)Thiourea (prevent Cuinterference)Ascorbic acid (reducing agent) | same |
| Measurementmethod | Bi-chromatic endpointmeasurement (600 and 700nm) | same |
| Calibration | Three point linear calibration | same |
| Analytical Range | 0 to 1,000 µg/dL | same |
| Standardization | NIST SRM 937 | same |
| Differences | ||
| Item | Device | Predicate |
| Matrix | Serum or heparinized plasma | Serum only |
J. Standard/Guidance Document Referenced
- Guidance;
Guidance for Industry and FDA Staff - Use of Symbols on Labels and in Labeling of In Vitro Diagnostic Devices Intended for Professional Use, 11/30/2004
Guidance for Industry and FDA Staff; Replacement Reagent and Instrument Family Policy, 12/11/2003
Format for Traditional and Abbreviated 510(k)s - Guidance for Industry and FDA Staff, 08/12/2005
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2. Standards;
| GP22-A | Continuous Quality Improvement Essential Management Approaches |
|---|---|
| ISO 15223 | Medical devices -- Symbols to be used with medical device labelingand information to be supplied |
| ISO 14971-2000 | Application of risk analysis to Medical devices |
| EP7-A | Interference Testing in Clinical Chemistry |
| EP5-A2 | Evaluation of Precision Performance of Clinical Chemistry Devices |
| CEN 13640 | Stability testing of In-Vitro Diagnostic Devices |
K. Test Principle:
The automated Dimension® IRON method is an adaptation of direct iron assays using the chromophore Ferene ® . Under acidic conditions, iron (Fe+++) bound to the protein transferrin is released. In the presence of the reducing agent ascorbic acid, (Fe+++) is reduced to (Fe++). (Fe ++) forms a blue complex with 3-(2-pyridyl)-5,6-bis-2-(5-furyl sulfonic acid)-1,2,4-triazine, disodium salt (Ferene®). The absorbance of the complex, measured using a bichromatic (600, 700 nm) endpoint technique, is directly proportional to the concentration of transferrin-bound iron in the serum.
L . Performance Characteristics:
- Precision/Reproducibility:
Reproducibility testing was done in accordance with the CLSI/NCCLS Approved Guideline for Evaluation of Precision Performance of Clinical Chemistry Devices (EPS-A2). Commercial controls and serum and plasma pools were analyzed in duplicate twice a day for 20 days. The repeatability and within-lab standard deviations were calculated by analysis of variance method.
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| Mean | Standard Deviation (%CV) | |||
|---|---|---|---|---|
| Material | µg/dL | [µmol/L] | Repeatability | Within-lab |
| Plasma pool | 101 | 18 | 0.5 [0.09] (0.5) | 0.7 [0.13] (0.7) |
| Serum pool 1 | 95 | 16.9 | 0.5 [0.09] (0.5) | 0.6 [0.11] (0.6) |
| Serum pool 2 | 316 | 56.6 | 1.5 [0.27] (0.5) | 3.5 [0.63] (1.1) |
| Serum pool 3 | 533 | 95.4 | 2.4 [0.43] (0.5) | 4.2 [0.75] (0.8) |
| BioRad Lyphochek® control Level 1 | 231 | 41.3 | 1.3 [0.23] (0.5) | 1.6 [0.29] (0.7) |
| BioRad Lyphochek® control Level 2 | 50 | 8.9 | 0.5 [0.09] (1.1) | 0.9 [0.16] (1.9) |
| BioRad Lyphochek® Anemia control Level 1 | 26 | 4.7 | 0.3 [0.05] (1.3) | 0.5 [0.09] (1.9) |
| Reduced Sample Volumec | ||||
| Serum pool 1 | 103 | 18.5 | 0.7 [0.13] (0.6) | 1.0 [0.18] (0.9) |
| Serum pool 2 | 316 | 56.6 | 1.5 [0.27] (0.5) | 3.5 [0.63] (1.1) |
| Serum pool 3 | 530 | 94.9 | 2.9 [0.52] (0.5) | 4.2 [0.75] (0.8) |
| BioRad Lyphochek® Anemia control Level 1 | 32 | 5.7 | 0.3 [0.05] (1.3) | 0.5 [0.09] (1.9) |
| BioRad Multiqual® control Level 3 | 231 | 41.3 | 1.6 [0.29] (0.7) | 2.2 [0.39] (0.9) |
Reproducibilityª,b
Lyphochek® and Multiqual® are registered trademarks of Bio-Rad Laboratories, Irvine, CA 92618.
- Reproducibility testing was done in accordance with the CLSI/NCCLS Approved a. Guideline for Evaluation of Precision Performance of Quantitative Measurement Methods (EP5-A2, 2004).
- Specimens at each level were analyzed in duplicate, twice a day, for 20 days. The b repeatability andwithin-lab standard deviations were calculated by analysis of variance method.
- Using reduced sample size (25 uL). C.
2. Linearity/assay reportable range:
Solutions of NIST SRM 937 were prepared by sequential mixing to create equally spaced samples ranging from 0 to 2000 µg/dL iron. The linearity of iron on the Dimension® RxL by the Dimension® IRON assay was evaluated by comparing observed versus expected values across the expected range. A linear regression analysis was performed on the data and plotted. The observed linearity across the reportable range has a correlation coefficient of 0.999 (using Pearson correlation calculation), slope of 0.999, and an intercept of 0.178. The assay range claim is 5.0 µg/dL to1000 µg/dL.
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- Traceability (controls, calibrators, or method):
The recommended reference material for the Dimension® IRON method is the Dimension® IRON Calibrator (Cat. No. DC85). The assigned values of this product are standardized to SRM NIST 937 Iron Metal Clinical Standard which is a Standard Reference Material of the National Institute of Standards & Technology.
4. Detection limit:
The analytical sensitivity of Dimension® IRON is 5 µg/dL [0.9 µmol/L]. The analytical sensitivity represents the lowest concentration of iron that can be distinguished from zero. This sensitivity is defined as the mean value (n=20) plus two standard deviations of the low level (0 ug/dL [0 umol/L] IRON Calibrator.
5. Analytical specificity:
Interference testing was performed according to the CLSI/NCCLS Protocol EP-7A. Systematic inaccuracies (bias) due to these substances are less than 10% at an iron concentration of 26 to 38 µg/dL [4.7 to 6.8 µmol/L] and 118 to 136 µg/dL [21.1 to 24.3 umol/L]. A summary of potential interfering substances and the substances that do not interfere with the Dimension® IRON method when present in serum at the concentrations indicated can be found in the package insert.
6. Method comparison with predicate device:
A total of 147 samples were tested using the Dimension® IRON and IRN assays on a Dimension® RxL clinical chemistry system. 99 individual patient serum samples and 48 individual patient serum samples that were spiked with various amounts of NIST-937 reference iron material were tested. Studies were performed using routine methods for quality control, maintenance and calibration as described in the instrument instructions for use.
Linear regression analysis was performed using the SAS® System. The model equation for regression statistics is: Result of Dimension® system = (Slope x comparative method result) + Intercept. The range of IRON values in the correlation study was: 9 to 963 ug/dL. The linear regression statistics are presented in the table below.
Method Comparison
| ComparativeMethod | Slope | Interceptug/dL | CorrelationCoefficient | n |
|---|---|---|---|---|
| Dimension®IRN (DF49A) | 0.980 | -0.488 | 0.9996 | 147 |
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7. Matrix comparison
129 matched specimens of serum and heparinized plasma were drawn and processed by the IRON method on the Dimension® clinical chemistry system. Linear regression analysis showed excellent agreement between serum, lithium heparin plasma and sodium heparin plasma specimens. No clinically significant difference was observed between serum and plasma samples.
Sodium heparin plasma versus serum: n = 129, y = 0.988x + 0.804, r = 0.999 Lithium heparin plasma versus serum: n = 129, y = 0.985x + 1.42, r = 0.999 Lithium heparin plasma verus sodium heparin plasma: n = 129, y = 0.997x + 0.666, r = 0.999
- Reference Interval
Males: 65-175 µg/dL [11.6-31.3 µmol/L]1
Females: 50-170 µg/dL [9.0- 30.4 µmol/L]1
Normal reference intervals can differ by as much as 35% between commercial iron methods2, therefore it is advised that each laboratory establish its own expected values for iron as performed on the Dimension® system.
- Kaplan LA, Psece AJ. Clinical Chemistry Theory, Analysis, and Correlation, 3th ed. St. 1. Louis: Mosby, Inc., 1996: p 699, 713-714.
- Burtis, CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular 2. Diagnostics, 4th ed. St. Louis: Elsevier Saunders, 2005, 1186-1193.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
MAR 8 2006
Food and Drug Administratio 2098 Gaither Road Rockville MD 20850
Ms. Andrea Tasker Regulatory Affairs and Compliance Manager Dade Behring Inc. Glasgow Business Community P.O. Box 6101, Bldg. 500, M/S 514 Newark, DE 19714-6101
Re: K060264
K000201
Trade/Device Name: Dimension® Iron Flex® reagent cartridge (IRON-DF85) Regulation Number: 21 CFR§862.1410 Regulation Name: Iron (non-heme) test system Regulatory Class: Class I Product Code: JIY Dated: January 30, 2006 Received: February 1, 2006
Dear Ms. Tasker:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave roviews your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for association 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 r ou mayy ators 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 either class II (Special Controls) or class III (PMA), 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 --
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 prarketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, rr you stions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Alberto Guts
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications For Use Statement
510(k) Number (if known):
Device Name:
Dimension® Iron Flex® reagent cartridge (IRON - DF85)
Indications for Use:
The IRON method for the Dimension® clinical chemistry system is an in The IRON method for the Ditton and to quantitatively measure iron in human serum and plasma. Iron measurements are used in the diagnosis and scrum and plasma. "I on measing deficiency anemia and other disorders of iron metabolism.
Concurrence of CDRH, Office of -In Vitro Điagnostic Devices (OIVD)
Prescription Use
(Per 21 CFR 801 Subpart D)
AND/OR
Over-the-counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANGTHER PLANTES NEEDED)
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Office of In Vitro Diagnostic Device Evaluation and Safety
060264
§ 862.1410 Iron (non-heme) test system.
(a)
Identification. An iron (non-heme) test system is a device intended to measure iron (non-heme) in serum and plasma. Iron (non-heme) measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.