DIMENSION EXL WITH LM SYSTEM
Device Facts
| Record ID | K130276 |
|---|---|
| Device Name | DIMENSION EXL WITH LM SYSTEM |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | JJE · Clinical Chemistry |
| Decision Date | Mar 22, 2013 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.2160 |
| Device Class | Class 1 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K130276 · Mar 22, 2013 | DIMENSION EXL WITH LM SYSTEM | Siemens Healthcare Diagnostics, Inc. | Remnant de-identified human serum samples | Remnant patient samples were used to conduct a split-sample method comparison to demonstrate substantial equivalence between the device with a new photomultiplier tube and the predicate device. | Method Comparison; Remnant Samples; Clinical Samples |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Split-sample method comparison | Human serum samples; Sample Size: 45; Number of Sites: 1 (Internal Siemens R&D) | Dimension® EXL™ with LM system with current photomultiplier tube (predicate) | Correlation coefficient, slope, and intercept of FT4L assay results |
Indications for Use
The Dimension® EXL™ with LM system is an in vitro diagnostic device that is intended to measure a variety of analytes in human body fluids. The system utilizes photometric, turbidimetric, chemiluminescence and integrated ion selective multisensory technology for chemical and immunochemical applications for clinical use. The FT4L method is an in vitro diagnostic test for the quantitative measurement of Free Thyroxine in human serum and plasma on the Dimension EXL™ with LM system. Measurements of free thyroxine are used in the diagnosis and monitoring of thyroid disease.
Device Story
Dimension® EXL™ with LM is a floor-model, fully automated, microprocessor-controlled clinical chemistry analyzer. It processes human serum and plasma samples using photometric, turbidimetric, chemiluminescent, and ion-selective multisensor technologies. The system utilizes prepackaged Flex® reagent cartridges. This submission specifically addresses a change in the photomultiplier tube (PMT) used for LOCI® chemiluminescent immunoassays. The LOCI® method involves a sequential reaction: sample incubation with biotinylated anti-T4 antibody; addition of T3-coated Chemibeads; and addition of streptavidin-coated Sensibeads. Illumination at 680 nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, producing a chemiluminescent signal at 612 nm inversely proportional to FT4 concentration. Operated by laboratory technicians in clinical settings, the system provides quantitative results to assist physicians in diagnosing and monitoring thyroid disease.
Clinical Evidence
Bench testing only. Precision evaluated over 20 days using commercial controls and patient pools; results showed comparable performance between new and current PMT. Linearity verified across 0.1–8.0 ng/dL range (R²=1.00). Method comparison against predicate using 45 patient samples showed high correlation (r=0.998, slope=0.97). Limit of Blank (LoB) verified at 0.03 ng/dL and Limit of Detection (LoD) at 0.06 ng/dL.
Technological Characteristics
Floor-model, fully automated, microprocessor-controlled analyzer. Uses LOCI technology (chemiluminescent immunoassay). Reagents: prepackaged Flex cartridges containing synthetic beads and biotinylated mouse monoclonal antibodies. Detection: Photomultiplier tube (enhanced glass single surface tube). Connectivity: LINUX-based system. Temperature control: 37°C for reactions, 2-8°C for reagent storage. Sample volume: 10 μL.
Indications for Use
Indicated for quantitative measurement of Free Thyroxine in human serum and plasma for diagnosis and monitoring of thyroid disease in patients.
Regulatory Classification
Identification
A discrete photometric chemistry analyzer for clinical use is a device intended to duplicate manual analytical procedures by performing automatically various steps such as pipetting, preparing filtrates, heating, and measuring color intensity. This device is intended for use in conjunction with certain materials to measure a variety of analytes. Different models of the device incorporate various instrumentation such as micro analysis apparatus, double beam, single, or dual channel photometers, and bichromatic 2-wavelength photometers. Some models of the device may include reagent-containing components that may also serve as reaction units.
Predicate Devices
- Dimension® EXL™ with LM system including FT4L assay (k073604)
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE
A. 510(k) Number:
k130276
B. Purpose for Submission:
Change to an existing device - Change in the photomultiplier tube (PMT) for Dimension EXL with LM system (previously cleared in k073604)
C. Measurand:
Free Thyroxine
D. Type of Test:
Quantitative, automated chemiluminescent immunoassay
E. Applicant:
Siemens Healthcare Diagnostics
F. Proprietary and Established Names:
Dimension FT4L Flex reagent cartridge
Dimension® EXL™ with LM System
G. Regulatory Information:
1. Regulation section:
21 CFR §862.1695, Free Thyroxine
21 CFR §862.2160, Discrete photometric chemistry analyzer for clinical use
2. Classification:
Class II, Class I
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3. Product code:
CEC, JJE
4. Panel:
Clinical Chemistry (75)
H. Intended Use:
1. Intended use(s):
See indications for use below
2. Indication(s) for use:
The Dimension® EXL™ with LM system is an in vitro diagnostic device that is intended to measure a variety of analytes in human body fluids. The system utilizes photometric, turbidimetric, chemiluminescence and integrated ion selective multisensory technology for chemical and immunochemical applications for clinical use.
The FT4L method is an in vitro diagnostic test for the quantitative measurement of Free Thyroxine in human serum and plasma on the Dimension EXL™ with LM system. Measurements of free thyroxine are used in the diagnosis and monitoring of thyroid disease.
3. Special conditions for use statement(s):
For prescription use only
4. Special instrument requirements:
Dimension® EXL™ with LM System
I. Device Description:
The Dimension EXL with LM system is a floor model, fully automated, microprocessor-controlled, integrated instrument which used prepackaged Siemens Dimension Flex reagent cartridges to measure a variety of analytes in human body fluids. The system can process samples in random access, batch or STAT modes. The instrument has a heterogeneous module (HM) for processing chromium-based heterogeneous immunoassays and a LOCI module (LM) for chemiluminescent immunoassays.
The test system remains the same except for the PMT. The PMT was modified by changing the supplier and the format of the multiplier channel was changed from multiple dynodes to enhanced glass single surface tube used to count the signal for the chemiluminescent methods.
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The Dimension® FT4L Flex® regent cartridge consists of prepackaged liquid reagents containing two synthetic beads, and a biotinylated anti-T4 mouse monoclonal antibody in a plastic eight-well cartridge
## J. Substantial Equivalence Information:
1. Predicate device name(s):
Dimension® EXL™ with LM system including FT4L assay
2. Predicate 510(k) number(s):
k073604
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device: Dimension® EXL™ with LM with new PMT | Predicate: Dimension® EXL™ with LM (k073604) |
| Intended/Indications for Use | The Dimension® EXL™ with LM system is an in vitro diagnostic device that is intended to measure a variety of analytes in human body fluids. The system utilizes photometric, Turbidimetric, chemiluminescence and integrated ion selective multisensor technology for chemical and immunochemical applications for clinical use. | Same |
| System Control | Fully automated and controlled by microprocessors | Same |
| User Interface | Contains graphical user interface screens | Same |
| Detection Technologies | Contains a photometer, a heterogeneous module and a multisensor electrode for performing photometric tests, and electrolyte tests. It also has a LOCI module for high sensitivity homogenous immunoassay tests. | Same |
| Reagents | Uses pre-packaged Flex reagent cartridges. Reagents are hydrated and stored on-board the instrument | Same |
| Temperature | Reagents are stored at 2-8°C. Reactions are controlled at 37°C. | Same |
| Operating System | LINUX Operating System | Same |
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| Differences | | |
| --- | --- | --- |
| Item | Device: Dimension® EXL™ with LM with new PMT | Predicate: Dimension® EXL™ with LM (k073604) |
| Photomultiplier tube used to amplify the signal in the chemiluminescent methods | Multiplier channel: multiple dynodes | Multiplier channel: Enhanced Glass Single Surface tube |
Similarities and Differences for Dimension® FT4L Flex® reagent cartridge
| Similarities and Differences | | |
| --- | --- | --- |
| Item | Device: Dimension® FT4L Flex® reagent cartridge | Predicate: Dimension® FT4L Flex® reagent cartridge (k073604) |
| Intended Use | The FT4L method is an in vitro diagnostic test for the quantitative measurement of Free Thyroxine in human serum and plasma on the Dimension® EXL™ with LM system. Measurements of free thyroxine are used in the diagnosis and monitoring of thyroid disease. | Same |
| Assay Range | 0.1-8.0 ng/dL | Same |
| Sample Type | Human serum and plasma | Same |
| Technology | LOCI® technology | Same |
| Sample size | 10 μL | Same |
| Reagents and antibody | There are three (3) reagents- Streptavidin sensibeads, T3 Chemibeads and FT4 biotinylated antibody (containing mouse monoclonal antibody) | Same |
K. Standard/Guidance Document Referenced (if applicable):
- CLSI-EP05-A: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline
- CLSI-EP09-A: Method Comparison and Bias Estimation Using Patient Samples: Approved Guideline
- In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submissions-Jan. 1997
- Format for Traditional and Abbreviated 510(k)'s-Guidance for Industry and Staff-Nov. 17, 2005 Guidance for Industry and FDA staff: Administrative Procedures for CLIA Categorization- May 7, 2008
L. Test Principle:
The Dimension EXL with LM system is a floor model, fully automated, microprocessor controlled, integrated instrument which uses prepackaged Siemens Dimension Flex® reagent
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cartridges to measure a variety of analytes in human body fluids. The system can process samples in random access, batch or STAT modes. The instrument has a heterogeneous module (HM) for processing chromium-based heterogeneous immunoassays and a LOCI® module for chemiluminescent immunoassays. The instrument can also perform photometric, turbidimetric and affinity column mediated immunoassay (ACMIA) tests.
The FT4L method is a homogeneous, sequential, chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated anti-T4 mouse monoclonal antibody. The first bead reagent (Chemibeads) is coated with triiodothyronine (T3), a naturally occurring, weaker binding analog of T4, and contains chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dye. In a first step, sample is incubated with biotinylated antibody which allows T4 from the sample to saturate a fraction of the biotinylated antibody that is directly related to the free thyroxine (FT4) concentration. In a second step, T3 Chemibeads are added and form bead/biotinylated antibody immunocomplexes with the non-saturated fraction of the biotinylated antibody. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the FT4 concentration in the sample.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
The precision study was conducted using three (3) commercial quality controls (BioRad Liquichek Immunoassay QC) and two (2) patient serum pools. Testing was performed over twenty (20) days, one (1) run per day for each test material on the Dimension EXL with LM systems with both the new and the current PMT. Analysis of variance was used to evaluate the data as outlined in CLSI EP5-A2 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline-Second Edition. The data is summarized below.
| Current PMT FT4L assay | | Repeatability (within-run) | | With-in Lab | |
| --- | --- | --- | --- | --- | --- |
| Sample | Mean (ng/dL) | SD (pg/mL) | %CV | SD (pg/mL) | %CV |
| Level 1 | 0.91 | 0.02 | 2.5 | 0.03 | 3.0 |
| Level 2 | 2.39 | 0.06 | 2.4 | 0.08 | 3.0 |
| Level 3 | 7.01 | 0.01 | 2.5 | 0.03 | 3.0 |
| Patient Pool 1 | 1.18 | 0.03 | 2.5 | 0.03 | 3.0 |
| Patient Pool 2 | 3.86 | 0.07 | 1.7 | 0.08 | 2.0 |
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| New PMT FT4L assay | | Repeatability (within-run) | | With-in Lab | |
| --- | --- | --- | --- | --- | --- |
| Sample | Mean (ng/dL) | SD (pg/mL) | %CV | SD (pg/mL) | %CV |
| Level 1 | 0.89 | 0.02 | 2.0 | 0.03 | 3.4 |
| Level 2 | 2.44 | 0.05 | 1.9 | 0.07 | 2.8 |
| Level 3 | 6.85 | 0.10 | 1.5 | 0.17 | 2.4 |
| Patient Pool 1 | 1.17 | 0.02 | 1.7 | 0.03 | 2.7 |
| Patient Pool 2 | 3.93 | 0.06 | 1.6 | 0.07 | 1.7 |
b. Linearity/assay reportable range:
The measuring range was determined using the Level 5 Thyroid Calibrator and the calibrator base matrix with the new PMT in accordance with CLSI Evaluation of Linearity of Quantitative Measure Procedures (EP06-A). Intermediate levels were prepared by proportional mixing of the high and low calibrator materials to produce concentrations evenly distributed across the assay range. Eleven concentration levels (ranging 0.1 to 8.32ng/dL) were assayed three times. The data was analyzed using least squares linear regression. The quadratic terms of the second and third order polynomial fit were statistically insignificant (p value >0.05), supporting linearity across the measuring range of 0.1 to 8.0ng/dL. The least squares linear regression analyses were: slope =1.04, y-intercept= -0.01, and R²=1.00.
c. Traceability, Stability, Expected values (controls, calibrators, or methods): Calibrator Traceability:
USP-grade thyroxine is spiked into stripped human serum at different concentrations. This becomes the "Anchor Pool". The "Anchor Pool" values are validated in-house.
A Master Pool is developed from stripped bovine albumin to which different concentrations of thyroxine have been added. Values for the Master Pool are derived by multiple analyses against the Anchor Pool calibration curve. LOCI® Thyroid Calibrator value assignment is established by measurement against the Master Pool calibration.
Calibrators have been previously cleared in k073604.
d. Detection limit:
To verify the limit of blank (LoB), twenty (20) replicates of the calibrator matrix material (0 ng/dL) were processed in a single batch run in accordance with CLSI EP17-A with the new PMT. None of the replicate measurements exceeded the LoB claim of 0.03ng/dL. The LoB claim was verified and established as 0.03ng/dL the reference concentration for LoD verification.
To verify the limit of detection (LoD), two samples were prepared at concentrations approximately equal to the LoD claim (0.06 ng/dL). The samples were processed in
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replicates of five for three testing days yielding a total of fifteen test measurements per sample. All replicate measurements exceeded the LoB claim. The LoD was determined to be 0.06 ng/dL.
e. Analytical specificity:
Provided in k073604
f. Assay cut-off:
Provided in k073604
2. Comparison studies:
a. Method comparison with predicate device:
Forty five (45) patient samples across the FT4L assay range were tested on modified and unmodified instruments. The results were analyzed by Passing Bablok and linear regression statistics. The correlation coefficient was obtained by linear regression. The summary of the method comparison data is presented below.
| Method | Range (ng/mL) | Slope (95% CI) | Intercept ng/dL (95% CI) | Correlation Coefficient (std linear regression) | n |
| --- | --- | --- | --- | --- | --- |
| FT4L (Passing Bablok) | 0.23-7.78 | 0.99 (0.96- 1.01) | -0.03 (-0.07-0.00) | Not applicable | 45 |
| FT4L (linear regression) | 0.23-7.78 | 0.97 | 0.00 | 0.998 | 45 |
b. Matrix comparison:
Provided in k073604
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
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4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
The expected values were transferred from that previously determined for the FT4 method on the Dimension Vista System. The values represent the central 95% of results determined non-parametrically from a population of 199 healthy adults (140 males and 59 females).
The expected values provided in the labeling are: 0.76-1.46 ng/dL.
N. Instrument Name:
Dimension® EXL™ with LOCI Module (LM) System
O. System Descriptions:
1. Modes of Operation:
Fully automated, microprocessor controlled, random access, batch and STAT modes
2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ X or No ☐
3. Specimen Identification:
Provided in k073604
4. Specimen Sampling and Handling:
Provided in k073604
5. Calibration:
Provided in k073604
6. Quality Control:
Provided in k073604
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P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:
Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
R. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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