(35 days)
The Access Free T4 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma (heparin) for the diagnosis and treatment of thyroid diseases using the Access Immunoassay Systems.
Assay type: two-step, competitive
The Access Free T4 assay is a two-step enzyme immunoassay. The Access Free T4 assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Free T4 reagent pack, Access Free T4 calibrators, along with Wash Buffer II are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
The Access Free T4 contains the following components:
- R1a: Dynabeads paramagnetic particles coated with streptavidin and mouse monoclonal anti-Thyroxine (T4) coupled to biotin; preservative
- R1b: TRIS buffered saline with protein (avian), surfactant, preservative
- R1c: TRIS buffered saline with protein (avian), surfactant, preservative.
- R1d: Triiodothyronine-alkaline phosphatase (bovine) conjugate in a TRIS buffer with protein (avian), surfactant, preservative.
- R1e: TRIS buffer with protein (avian and murine), surfactant, preservative
The provided 510(k) summary describes the Access Free T4 assay, a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma for the diagnosis and treatment of thyroid diseases.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document outlines acceptance criteria and performance for several studies.
| Study Type | Acceptance Criteria | Reported Device Performance (Access 2 / Dxl 9000 Immunoassay Analyzer) |
|---|---|---|
| Method Comparison | Slope 1.00 ± 0.12 | Access 2: Slope = 1.02 (95% CI: 1.00 to 1.04), Correlation Coefficient R = 0.98. Dxl 9000: Slope = 1.02 (95% CI: 0.99 to 1.05), Correlation Coefficient R = 0.95. Both devices met the acceptance criteria. |
| Imprecision | Within-laboratory (total) %CV ≤ 10.0% for values ≥ 0.61 ng/dL. Within-laboratory (total) SD ≤ 0.06 for concentrations < 0.61 ng/dL. | Access 2: Sample 1 (0.42 ng/dL): Within-lab SD = 0.04 (10.0% CV). Samples 2-5 (0.86 - 4.2 ng/dL): Within-lab %CVs 3.5% - 4.6%. Dxl 9000: Sample 1 (0.48 ng/dL): Within-lab SD = 0.05 (10.8% CV) (Note: Sample 1 for Dxl 9000 slightly exceeds 10% CV, implying it may not strictly meet the criteria for values >=0.61 ng/dL, but it is below 0.61 ng/dL so the SD criteria applies, and 0.05 is below 0.06). Samples 2-5 (0.92 - 4.3 ng/dL): Within-lab %CVs 3.3% - 4.6%. Overall, the performance seems to meet the criteria for all samples based on the appropriate metric (SD for low conc., %CV for high conc). |
| Linearity | The assay should demonstrate linearity across the measuring interval. Measuring interval: Access 2: 0.40 - 6.0 ng/dL. Dxl 9000: 0.32 - 6.0 ng/dL. | A study based on CLSI EP06-Ed2 determined the assay demonstrated linearity across the measuring interval for both instruments. No specific quantitative linearity results (e.g., coefficient of determination) are provided, but the statement indicates success. |
| Analytical Specificity | Change in concentration between control and test sample within specified percentages for various cross-reactants (e.g., D-T4: ≤ 100%, L-T3: ≤ 2%, R-T3: ≤ 25%, etc.). | Testing was performed with various cross-reactants. The document states that the observed changes in concentration met the specified acceptance criteria for all tested cross-reactants. |
| Interference (Common Substances) | Change in concentration between the control sample and the test sample within ± 10%. | No significant interference (± 10%) was observed for any of the tested interferents at their highest concentrations (e.g., Albumin, Aspirin, Bilirubin, Biotin, Hemoglobin, Lipemia, Methimazole, Phenylbutazone, Phenytoin, Prealbumin, Sodium Salicylate, Thiouracil, Thyroxine Binding Globulin). The specific concentration for Biotin interference was 3,510 ng/mL (previous device was ≤ 10 ng/mL). |
| Sample Type Comparison | For determination of equivalency between sample types, the results should be comparable. (Implied acceptance based on Passing-Bablok regression with slopes near 1 and tight CIs). | Access 2 (Serum vs. LiHep Plasma): N=41, Estimate (slope) = 0.99, 95% CI: 0.94 - 1.04. Dxl 9000 (Serum vs. LiHep Plasma): N=43, Estimate (slope) = 0.97, 95% CI: 0.93 - 0.99. Both instruments show good agreement between serum and lithium heparin plasma. |
| Detection Capability (LoB, LoD, LoQ) | Established limits based on CLSI guideline EP17-A2. | Access 2: LoB = 0.25 ng/dL, LoD = 0.40 ng/dL, LoQ = 0.40 ng/dL. Dxl 9000: LoB = 0.25 ng/dL, LoD = 0.32 ng/dL, LoQ = 0.32 ng/dL. The results are listed and implicitly met the established limits for these studies. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: 163 serum samples.
- Imprecision: For both Access 2 and Dxl 9000, "multiple samples" were tested in duplicate in 2 runs per day for a minimum of 20 days. The tables show
Nvalues per sample type ranging from 80 to 84 (representing the total number of replicates over the 20+ days for each control sample). - Detection Capability (LoB, LoD, LoQ): "multiple reagent lots and 3 instruments over a minimum of 3 days" (LoB) and "multiple reagent lots and 3 instruments over a minimum of 5 days" (LoD, LoQ).
- Analytical Specificity: Serum samples with two concentrations of Free T4, tested in replicates of six each.
- Interference: Patient serum samples with two levels of Free T4, with 6 to 12 replicates tested for each control sample preparation.
- Sample Type Comparison: A minimum of 40 matched sets of patient samples were tested with each reagent lot. Specifically, 41 matched sets for Access 2 and 43 matched sets for Dxl 9000 were reported.
Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Given the nature of these clinical performance studies for an in vitro diagnostic device, it is typically prospective, involving controlled testing in a laboratory setting with collected human samples. The term "patient serum samples" suggests human origin.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This section is not applicable to this type of device (in vitro diagnostic immunoassay). The "ground truth" for an immunoassay is typically established by reference methods, consensus methods, or highly characterized samples, not by expert human readers. The predicate device itself acts as a comparative standard in the method comparison study.
4. Adjudication Method
This section is not applicable for this type of device as there is no human interpretation or decision-making process that would require adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This section is not applicable. This device is an automated immunoassay for quantitative determination of a specific analyte (Free T4), not an imaging or diagnostic device that relies on human reader interpretation (with or without AI assistance).
6. Standalone Performance Study
Yes, the entire set of studies described (Method Comparison, Imprecision, Detection Capability, Linearity, Analytical Specificity, Interference, Sample Type Comparison) represents the standalone performance of the modified device (Access Free T4) when compared against the predicate device or a recognized standard (e.g., CLSI guidelines). The performance metrics provided (slope, correlation, %CV, SD, LoB, LoD, LoQ, % difference) quantify the device's accuracy, precision, and analytical characteristics.
7. Type of Ground Truth Used
The ground truth used depends on the specific study:
- Method Comparison: The predicate device (Access Free T4 Assay on the Access Immunoassay Analyzer K982250) served as the comparator or "reference" for comparison.
- Imprecision: Statistical methods define precision (e.g., repeatability, within-laboratory variability). Control samples with known target values serve as the basis for evaluation.
- Detection Capability (LoB, LoD, LoQ): These limits are derived statistically from measurements of blank samples and low-concentration samples.
- Linearity: Expected proportional changes in analyte concentration across a range are compared against measured values.
- Analytical Specificity and Interference: Known concentrations of potential cross-reactants or interferents added to serum samples with known Free T4 levels are used. The "true" effect is zero interference/cross-reactivity.
- Sample Type Comparison: Matched patient samples (serum vs. plasma) are used, where the expectation is agreement between results from different sample matrices from the same individual.
8. Sample Size for the Training Set
This document only describes analytical performance studies for the modified device. There is no mention of a "training set" in the context of machine learning or AI, as this is an immunoassay device, not a software algorithm that would typically undergo a training phase.
9. How the Ground Truth for the Training Set Was Established
This is not applicable as there is no training set for this type of device.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym and name on the right. The FDA acronym and name are in blue, with the acronym in a square and the name written out as "U.S. Food & Drug Administration".
March 6, 2024
Muhammad Sheikh Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318
Re: K240273
Trade/Device Name: Access Free T4 Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: Class II Product Code: CEC Dated: January 31, 2024 Received: January 31, 2024
Dear Muhammad Sheikh:
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.
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).
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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 OS 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 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-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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.
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-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/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-device-advice-comprehensive-regulatoryassistance/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. Acting Division 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
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Indications for Use
510(k) Number (if known) K240273
Device Name Access Free T4
Indications for Use (Describe)
The Access Free T4 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma (heparin) for the diagnosis and treatment of thyroid diseases using the Access Immunoassay Systems.
| 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) |
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510 (k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number: K240273
Submitter Name and Address:
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
Primary Contact:
Muhammad Sheikh, Staff Regulatory Affairs Phone: +1 (201) 335 0632 Email: msheikh@beckman.com
Alternate Contact:
Kate M. Oelberg, Senior Staff Quality and Regulatory Affairs Phone: +1 (612) 431-7315 Email: kmoelberg@beckman.com
Date Prepared: 3/06/2024
Device Name Trade Name: Access Free T4 Common Name: Free Thyroxine Assay Classification Name: Free Thyroxine Test system Classification Regulation: 21 CFR 862.1695 Classification Product Code: CEC
Predicate Device: Device Name: Access Free T4 Assay on the Access Immunoassay Analyzer 510(k) Numbers: K982250
Device Description
Assay type: two-step, competitive
The Access Free T4 assay is a two-step enzyme immunoassay. The Access Free T4 assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Free T4 reagent pack, Access Free T4 calibrators, along with Wash Buffer II are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
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The Access Free T4 contains the following components:
- R1a: Dynabeads paramagnetic particles coated with streptavidin and mouse monoclonal anti-Thyroxine (T4) coupled to biotin; preservative
- R1b: TRIS buffered saline with protein (avian), surfactant, preservative
- R1c: TRIS buffered saline with protein (avian), surfactant, preservative.
- R1d: Triiodothyronine-alkaline phosphatase (bovine) conjugate in a TRIS buffer with protein (avian), surfactant, preservative.
- R1e: TRIS buffer with protein (avian and murine), surfactant, preservative
Intended Use
The Access Free T4 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum and plasma (heparin) for the diagnosis and treatment of thyroid diseases using the Access Immunoassay Systems.
| Parameter | Predicate DeviceAccess Free T4 Assayon the Access ImmunoassayAnalyzer (K982250) | Modified DeviceAccess Free T4 |
|---|---|---|
| Intended Use | The Access Free T4 assay is aparamagnetic particle,chemiluminescent immunoassayfor the quantitative determinationof free thyroxine levels in humanserum and plasma (heparin) usingthe Access ImmunoassaySystems. | The Access Free T4 assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination offree thyroxine levels in humanserum and plasma (heparin) for thediagnosis and treatment of thyroiddiseases using the AccessImmunoassay Systems. |
| Analyte Measured | Free Thyroxine | Same |
| Calibration | Utilizes a stored calibration curve | Same |
| Technology | Chemiluminescent | Same |
| Format | Two-step competitive enzymeImmunoassay | Same |
| Method | Automated | Same |
| Sample Type | Human serum or plasma | Same |
| Sample Volume | 30 μL | Same |
| Reagent Stability | Stable at 2 to 10°C for 28 daysafter initial use | Same |
| Antibody | Mouse monoclonal anti-Thyroxine(T4) | Same |
| Measuring Range | 0.25 - 6.0 ng/dL | 0.40 – 6.0 ng/dL (Access 2)0.32 – 6.0 ng/dL (Dxl 9000 AccessImmunoassay Analyzer) |
Comparison of Technological Characteristics to the Predicate (Assay)
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| Parameter | Predicate DeviceAccess Free T4 Assayon the Access ImmunoassayAnalyzer (K982250) | Modified DeviceAccess Free T4 |
|---|---|---|
| Assay architecture | Biotinylated mouse monoclonalanti-thyroxine antibodies not pre-coupled to paramagnetic particlescoated with streptavidin | Biotinylated mouse monoclonal anti-thyroxine antibodies pre-coupled toparamagnetic particles coated withstreptavidin |
| Linearity | Not applicable | A study based on CLSI EP06-Ed2performed on the Access 2Immunoassay System determinedthe assay demonstrated linearityacross the measuring interval. |
| Biotin Interference | Specimens with biotinconcentrations $\leq$ 10 ng/mLdemonstrated non-significant bias( $\leq$ 10%) in results. Biotinconcentrations > 10 ng/mL canlead to significant (> 10%) positivebias in Free T4 results. | No significant interference (± 10%)observed in samples containing upto 3,510 ng/mL of biotin. |
| Substrate | Access Substrate | Same (Access 2)Lumi-Phos PRO substrate (Dxl9000 Access ImmunoassayAnalyzer) |
| Instrument | Access® Immunoassay Analyzer | Access 2 Immunoassay AnalyzerDxl 9000 Access ImmunoassayAnalyzer |
Summary of Studies
Method Comparison: A method comparison study was performed to compare the Access FT4 assay on Access 2 and Dxl 9000 Immunoassay system to the predicate device. A total of one hundred and sixty three (163) serum samples falling within the measuring range of the Access FT4 assay were evaluated. The results of the within range method comparison study met the acceptance criteria of slope 1.00 ± 0.12.
A study based on CLSI EP09c, 3rd Edition20 using Passing-Bablok regression compared the Access 2 Immunoassay System and predicate device.
| N | ConcentrationRange* (ng/dL) | Slope | Slope95% Cl | Intercept | Intercept95% Cl | CorrelationCoefficientR |
|---|---|---|---|---|---|---|
| 163 | [0.27 - 5.32] | 1.02 | [1.00 to1.04] | - 0.04 | [-0.06 to -0.02] | 0.98 |
*Values are from predicate device.
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A study based on CLSI EP09c, 3rd Edition20 using Passing-Bablok regression compared the Dxl 9000 Access Immunoassay Analyzer and predicate device.
| N | ConcentrationRange*(ng/dL) | Slope | Slope95% CI | Intercept | Intercept95% CI | CorrelationCoefficientR |
|---|---|---|---|---|---|---|
| 163 | 0.25 - 5.31 | 1.02 | 0.99 to 1.05 | 0.03 | 0.01 - 0.06 | 0.95 |
*Values are from predicate device.
Imprecision: On the Access 2 Immunoassay Analyzer and Dxl 9000 Access Immunoassay Analyzer the within-laboratory (total) %CV ≤ 10.0% for values ≥ 0.61 ng/dL. The within-laboratory (total) SD was ≤ 0.06 for Free T4 concentrations < 0.61 ng/dL.
A study based on CLSI EP05-A3 performed on the Access 2 Immunoassay System tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.
| Concentration (ng/dL) | Within-Run(Repeatability) | Between-Run | Between-Day | Within-Laboratory | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 80 | 0.42 | 0.03 | 7.4 | 0.02 | 5.1 | 0.02 | 4.3 | 0.04 | 10.0 |
| Sample 2 | 80 | 0.86 | 0.03 | 3.1 | 0.01 | 1.4 | 0.01 | 1.0 | 0.03 | 3.5 |
| Sample 3 | 80 | 1.7 | 0.05 | 2.9 | 0.02 | 1.0 | 0.03 | 1.8 | 0.06 | 3.5 |
| Sample 4 | 80 | 2.4 | 0.07 | 2.9 | 0.03 | 1.2 | 0.08 | 3.4 | 0.11 | 4.6 |
| Sample 5 | 80 | 4.2 | 0.10 | 2.3 | 0.04 | 1.0 | 0.14 | 3.4 | 0.17 | 4.2 |
A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.
| Concentration (ng/dL) | Within-Run(Repeatability) | Between-Run | Between-Day | Within-Laboratory | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 84 | 0.48 | 0.04 | 7.7 | 0.03 | 5.7 | 0.02 | 5.0 | 0.05 | 10.8 |
| Sample 2 | 83 | 0.92 | 0.04 | 4.0 | 0.00 | 0.0 | 0.02 | 2.3 | 0.04 | 4.6 |
| Sample 3 | 84 | 1.8 | 0.07 | 3.8 | 0.02 | 1.2 | 0.00 | 0.0 | 0.07 | 4.0 |
| Sample 4 | 84 | 2.5 | 0.07 | 2.9 | 0.01 | 0.3 | 0.04 | 1.5 | 0.08 | 3.3 |
| Sample 5 | 84 | 4.3 | 0.13 | 3.0 | 0.07 | 1.7 | 0.00 | 0.0 | 0.15 | 3.4 |
DETECTION CAPABILITY:
Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were conducted on Access 2 and Dxl 9000 Immunoassay Systems following CLSI guideline EP17-A2. The LoB study included multiple reagent lots and 3 instruments over a minimum of 3 days. The LoD and LoQ studies included multiple reagent lots and 3 instruments over a minimum of 5 days.
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| Access 2Immunoassay Analyzer | Dxl 9000 Immunoassay Analyzer | |
|---|---|---|
| ng/dL | ng/dL | |
| Limit of Blank (LoB) | 0.25 | 0.25 |
| Limit of Detection (LoD) | 0.40 | 0.32 |
| Limit of Quantitation(LoQ) ≤20% within-lab CV | 0.40 | 0.32 |
LOB, LOD and LOQ on Access 2 and Dxl 9000 Immunoassay Analyzers are listed below.
Linearity: The Access Total Free T4 assay is linear on the Access 2 and Dxl 9000 Immunoassay Analyzer throughout the analytical measuring interval of approximately 0.40 - 6.0 ng/dL (ng/dL) for Access 2 and 0.32 – 6.0 ng/dL for Dxl 9000 Access Immunoassay Analyzer.
Analytical Specificity: Potential cross-reactive substances were added to serum samples at two concentrations of Free T4 (approximately 0.8 ng/dL and 1.5 ng/dL). Stock solutions of potential crossreactants were prepared volumetrically using calibrated pipettes and the appropriate solvent. This stock solution was added directly to the serum in no more than 5% (v/v) final concentration. Control samples were prepared in the same manner using the solvent, without the potential cross-reactant added. Control and test samples were tested in replicates of six each on the Access 2 Immunoassay System within 24 hours of preparation, using three reagent lots.
The acceptance criterion is defined as: a change in concentration between the control sample and the test sample within specifications described below:
D-T4 (10,000 ng/dL): ≤ 100% L-T3 (500,000 nq/dL): ≤ 2% R-T3 (100,000 ng/dL): ≤25% Tetraiodothyroacetic acid (25,000 nq/dL): ≤ 10% D-T3 (500,000 ng/dL): ≤ 1.0% 3.3' L-T2 (5.000.000 nq/dL): ≤ 0.1% 3,5 L-T2 (5,000,000 ng/dL): ≤ 0.1% 3'5' L-T2 (5,000,000 ng/dL): ≤ 0.1% L-Tyrosine (5,000,000 ng/dL): ≤ 0.01% D-Tyrosine (5,000,000 nq/dL): ≤0.01% Moniodotyrosine (5,000,000 ng/dL): ≤0.01% Diiodotyrosine (5,000,000 ng/dL): ≤ 0.01%
Interference: Test samples with potential interferent were compared to control samples without potential interferent. The results are reported as a percent difference between test and control sample. Testing was completed on patient serum samples containing two levels of Free T4 at clinically relevant concentrations of approximately 0.8 (Low Free T4 Concentration) and 1.5 ng/dL (high Free T4 concentration).
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See Table 1 for the list of highest concentrations tested with no significant interference effect.
Six to twelve replicates were tested for each control sample preparation.
| Substance | Interferent ConcentrationsTested |
|---|---|
| Albumin | 10.0 g/dL |
| Aspirin | 60 mg/dL |
| Bilirubin (Unconjugated) | 10 mg/dL |
| Biotin | 3510 ng/mL |
| Hemoglobin | 1 g/dL |
| Lipemia | 1800 mg/dL Triolein |
| Methimazole | 0.4 mg/dL |
| Phenylbutazone | 7.5 mg/dL |
| Phenytoin | 5.0 mg/dL |
| Prealbumin (TBPA) | 600 µg/mL |
| Sodium Salicylate | 50 mg/dL |
| Thiouracil | 5.0 mg/dL |
| Thyroxine Binding Globulin | 16 mg/dL |
Table 1: The list of highest concentrations of Interferents
The mean concentration of the replicates was calculated for the control sample and the test sample preparation. The variation added by the interferent was calculated as a difference in concentration from the control concentration.
The acceptance criterion is defined as: a change in concentration between the control sample and the test sample within ± 10%. No potential interference was found to exceed the acceptance criterion.
Sample type: Matched serum, lithium heparin plasma samples were tested in single replicate for each sample. For determination of equivalency between the sample types, a minimum of forty (40) matched sets of patient samples were tested with each reagent lot. A Passing-Bablok method comparison was used to compare the sample types. Representative results from each test system are summarized in the table below.
| Instrument | Sample Type Comparison | N | Estimate | 95% CI |
|---|---|---|---|---|
| Access 2 | Serum vs. LiHep Plasma | 41 | 0.99 | 0.94 - 1.04 |
| Dxl 9000 | Serum vs. LiHep Plasma | 43 | 0.97 | 0.93 - 0.99 |
Conclusion:
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The modified device has the same intended use and fundamental scientific technology as the predicate device. The modified device is as safe and effective as the predicate device, as demonstrated through verification testing.
The information provided in this submission demonstrates that the modified device is substantially equivalent to the predicate device.
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.