(49 days)
For the in vitro quantitative determination of total triiodothyronine (T3) in human serum and plasma.
The Elecsys® T3 employs a competitive test principle with polyclonal antibodies directed against T3 and with streptavidin microparticles and electrochemiluminescence detection. Total duration of assay: 18 minutes.
• 1st Incubation: Sample (30 µl) and specific anti-T3 antibodies labeled with a ruthenium complex together with ANS to release T3 from serum.
• 2nd Incubation: After the addition of streptavidin-coated microparticles and biotinylated T3, the still-free binding sites of the labeled antibody become occupied, with formation of an antibody-hapten complex. The entire complex is bound to the solid phase via interaction of biotin and streptavidin.
• The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
• Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's a summary of the acceptance criteria and study information for the Elecsys T3 device, based on the provided 510(k) summary:
The document does not explicitly state "acceptance criteria" in a pass/fail format, but rather presents performance characteristics of the new device (Elecsys T3) and compares them to a predicate device (Enzymun-Test® T3). The implicit acceptance criteria appear to be substantial equivalence, demonstrated by similar performance characteristics.
1. Table of Acceptance Criteria and Reported Device Performance
| Feature | Elementys T3 Performance (New Device) | Predicate Device (Enzymun-Test® T3) Performance | Implicit Acceptance Criteria (Demonstrates Substantial Equivalence if similar) |
|---|---|---|---|
| Precision | |||
| Within-run % CV | PC U1: 4.1%, PC U2: 3.5%, HS1: 3.6%, HS2: 4.2%, HS3: 5.3% | 1: 2.9%, 2: 1.6%, 3: 1.7% | Similar or better precision (lower % CV) across different sample concentrations. While some Elecsys T3 values are higher, they are generally in the same range, suggesting acceptable performance. |
| Total run % CV | PC U1: 4.8%, PC U2: 4.1%, HS1: 5.4%, HS2: 4.7%, HS3: 5.4% | 1: 4.7%, 2: 2.2%, 3: 2.8% | Similar or better precision (lower % CV) across different sample concentrations. |
| Sensitivity | Lower Detection Limit: 0.3 nmol/l (0.19 ng/ml) | Lower Detection Limit: 0.46 nmol/l (0.3 ng/ml) | Sensitivity should be comparable or better. Elecsys T3 demonstrates better (lower) detection limit. |
| Assay Range | 0.3 - 10.00 nmol/l (0.19 - 6.51 ng/ml) | 0.46 - 9.22 nmol/l (0.3 - 6.0 ng/ml) | Assay range should be comparable. Elecsys T3 offers a slightly broader range at the upper end and a lower detection limit. |
| Method Comparison | vs. Enzymun-Test T3 (Cat. # 1360868):Least Squares: N = 300, y = -0.35 + 1.18x, r = 0.957Passing/Bablok: N = 300, y = -0.56 + 1.26x, r = 0.957vs. Enzymun-Test T3 (Cat. # 1135287):Least Squares: N = 55, y = 1.13x + 0.02, r = 0.994 | (This section compares the new device to the predicate, so the predicate itself isn't a comparison target here, but the data it generated is used for comparison) | Correlation coefficients (r) close to 1, and slope (x) close to 1 with intercept (y) close to 0, indicating strong agreement between the new device and the predicate. The reported 'r' values of 0.957 and 0.994 suggest very good correlation. |
| Interfering Substances | Hemoglobin: 1 g/dlLipemia: 1500 mg/dlBilirubin: 25 mg/dlBiotin: 20 ng/ml | Hemoglobin: 1 g/dlLipemia: 1250 mg/dlBilirubin: 65 mg/dlBiotin: 50 ng/ml | Acceptable levels of interference for common substances. Elecsys T3 shows comparable or improved tolerance for some interferents (e.g., lipemia) and slightly lower tolerance for others (bilirubin, biotin), but within a clinically acceptable range as demonstrated by the predicate. |
| Specificity (% cross-reaction) | D-T3: 98.9%, L-T4: 0.115%, D-T4: 0.115%, L-rT3: 0.007%, L-T2: 0.998%, 3,3',5-tri-iodothyroacetic acid: 106.4%, 3,3',5,5'-tetra-iodothyroacetic acid: 0.007% | D-T3: 100%, L-T4: 0.16%, D-T4: 0.07%, L-rT3: 0.04%, L-T2: 1.0%, 3,3',5-tri-iodothyroacetic acid: 7.5%, 3,3',5,5'-tetra-iodothyroacetic acid: 0.01% | High specificity for T3 and low cross-reactivity with related substances, comparable to the predicate. The values are very close, indicating similar performance. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly define a "test set" in the context of an AI/algorithm-driven device. Instead, it describes performance characteristics determined through various studies.
- Precision Studies (NCCLS modified EP5-T2 for Elecsys T3, Modified NCCLS "Midi" EP3-T for Enzymun-Test T3):
- Elecsys T3 Sample Size (N): 60 for each of the 5 samples (PC U1, PC U2, HS1, HS2, HS3). This suggests 60 replicates or measurements per sample, likely conducted over multiple runs/days as indicated by "total run % CV".
- Enzymun-Test® T3 Sample Size (N): 118, 120, 117 for 3 different samples.
- Method Comparison Studies:
- Elecsys T3 vs. Enzymun-Test T3 (Cat. # 1360868): N = 300
- Elecsys T3 vs. Enzymun-Test T3 (Cat. # 1135287): N = 55
- Data Provenance: Not explicitly stated, but clinical studies for such devices typically involve human serum and plasma samples. The specific country of origin or whether the data was retrospective or prospective is not provided. It's common for these types of studies to be prospective, collecting samples specifically for the validation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This device is an in vitro diagnostic (IVD) assay for quantitative determination of a hormone, not an imaging or diagnostic algorithm that relies on expert interpretation for ground truth. Therefore, there were no "experts" establishing ground truth in the traditional sense for a test set typically associated with AI/ML devices. The "ground truth" for quantitative assays is established by the reference method or by comparing against a well-established predicate device, which is what was done here.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is a quantitative assay, and ground truth is based on measurements and comparison to a predicate device, not expert adjudication of cases.
5. 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 device is an in vitro diagnostic analyzer (an automated assay), not an AI-powered image analysis or diagnostic aid requiring human readers for interpretation. Therefore, an MRMC study or assessment of human reader improvement with AI assistance is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself is a standalone algorithm/assay in its operation. The Elecsys T3 system performs the measurement and provides a quantitative result. There is no human "in the loop" during the primary measurement process beyond loading samples and reagents, and interpreting the final quantitative value. The performance characteristics described (precision, sensitivity, assay range, method comparison, interfering substances, specificity) are all measures of its standalone analytical performance.
7. The Type of Ground Truth Used
The ground truth used for performance evaluation is primarily:
- Reference measurements/Predicate Device Comparison: The performance of the Elecsys T3 was compared directly against a legally marketed predicate device, the Enzymun-Test® T3. This comparison (method comparison studies) serves as the primary ground truth for demonstrating substantial equivalence.
- Defined concentrations/standards: For precision, sensitivity, and assay range, the "ground truth" comes from precisely prepared samples with known concentrations (e.g., control samples, diluted samples).
- Interfering substances/specificity panels: For these studies, the ground truth is the presence of known interfering substances or related compounds at specific concentrations, allowing the device's response to be assessed.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI. This is a traditional IVD device, not an AI/ML diagnostic. The development of such assays involves extensive R&D and optimization, but not typically a "training set" like in deep learning.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the AI/ML sense for this traditional IVD device. The development process would rely on biochemical principles, empirical optimization, and validation against established reference methods or predicate devices.
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AUG 1 5 1996
510(k) Summary
Image /page/0/Picture/2 description: The image shows a logo for Boehringer Mannheim. The logo consists of a black square with the word "mannheim" written vertically along the left side. Inside the square is a white circle with the word "boehringer" written horizontally across the center of the circle.
人962508
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
|---|---|
| 1) Submittername, address,contact | Boehringer Mannheim Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000 |
| Contact Person: LeeAnn Chambers | |
| Date Prepared: June 24, 1996 | |
| 2) Device name | Proprietary name: Elecsys T3 |
| Common name: Total triiodothyronine test system | |
| 3) Predicatedevice | We claim substantial equivalence to the Enzymun-Test® T3. |
| 4) DeviceDescription | The Elecsys® T3 employs a competitive test principle with polyclonalantibodies directed against T3 and with streptavidin microparticles and electrochemiluminescence detection.Total duration of assay: 18 minutes.• 1st Incubation: Sample (30 µl) and specific anti-T3 antibodies labeled with a ruthenium complex together with ANS to release T3 from serum.• 2nd Incubation: After the addition of streptavidin-coated microparticles and biotinylated T3, the still-free binding sites of the labeled antibody become occupied, with formation of an antibody-hapten complex. The entire complex is bound to the solid phase via interaction of biotin and streptavidin. |
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Image /page/1/Figure/0 description: The image shows the number 4760000 at the top. Below that is a logo for Boehringer Mannheim. The logo is a black square with a white circle in the middle. The words "boehringer" are written in the center of the circle, and the words "mannheim" are written vertically on the left side of the square.
AUG | 5 1996
510(k) Summary, Continued
| 4) DeviceDescription(cont.) | • The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed with ProCell. Application of avoltage to the electrode then induces chemiluminescent emission which ismeasured by a photomultiplier.• Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve providedvia the reagent bar code. |
|---|---|
| 5) Intended use | For the in vitro quantitative determination of total triiodothyronine (T3) inhuman serum and plasma. |
| 5) Indicationsfor use | Triiodothyronine (T3) is the hormone principally responsible for thedevelopment of the effects of the thyroid hormones on the various targetorgans. |
| T3 (3.5,3' Triiodothyronine) is mainly formed extra-thyroidally, particularlyin the liver, by enzymatic 5'-deiodination of T4. Accordingly, the T3concentration in serum is more a reflection of the functional state of theperipheral tissue than the secretory performance of the thyroid gland. | |
| A reduction in the conversion of T4 to T3 results in a fall in the T3concentration. It occurs under the influence of medications such aspropanolol, glucocorticoids or amiodarone and in severe non-thyroidalgeneral diseases - "non-thyroidal illness" (NTI) - and is referred to as the"low T3 syndrome." Like T4, over 99% of T3 is bound to transport proteins,but its affinity to them is around 10-fold lower.1-3,7 | |
| Continued on next page |
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510(k) Summary, Continued
| 5) Indicationsfor use | The determination of T3 is utilized in the diagnosis of T3-hyperthyroidism,the detection of early stages of hyperthyroidism and for indicating a diagnosisof thyrotoxicosis factitia.4-6 | ||||
|---|---|---|---|---|---|
| References1 Wheeler MH, Lazarus JH. Diseases of the Thyroid. Chapman and HallMedical. London Glasgow Weinheim New York Tokyo Melbourne Madras1994;107-115.2 Pfannenstiel P, Saller B. Schilddrüsenkrankheiten Diagnose und Therapie.Berliner Medizinische Verlagsanstalt GmbH 1995; 2:30-32,60-62.3 Fisher DA. Physiological variations in thyroid hormones physiological andpathophysiological considerations. Clinical Chemistry 1996;42:135-139.4 Klee GG. Clinical usage recommendations and analytic performance goals fortotal and free triiodothyronine measurements. Clinical Chemistry 1996;42:155-159.5 Surks MI, Chopra IJ, Mariash CN, Nicoloff JT, Solomon DH. AmericanThyroid Association guidelines for use of laboratory tests in thyroid disorders.JAMA 1990;63:1529-1532.6 Becker DV, Bigos ST, Gaitan E, Morris JC, Rallison ML, Spencer CA, et at.Optimal use of blood tests for assessment of thyroid function (letter). JAMA1993. 269:273.7. Wild D. The Immunoassay Handbook. Stockton Press 1994; 338. | |||||
| 6) Comparisonto predicatedevice | The Boehringer Mannheim Elecsys T3 is substantially equivalent to otherproducts in commercial distribution intended for similar use. Most notably itis substantially equivalent to the currently marketed Enzymun-Test® T3.Similarities: Intended use: immunoassay for the in vitro quantitative determination ofTotal Triiodothyronine (T3) Competitive test principle Sample type: serum and plasma Antibody: sheep anti-T3 polyclonal Capture principle: streptavidin / biotin |
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510(k) Summary, Continued
- Comparison to predicate device (cont.)
Differences:
| Feature | Elecsys T3 | Enzymun-Test T3 |
|---|---|---|
| Reaction testprinciple | streptavidin microparticles andelectrochemiluminescencetechnology | streptavidin-coated tubes andenzyme immunoassaytechnology |
| Samplevolume | 30 µl | 100 µl |
| Instrumentrequired | Elecsys 2010 | ES 300 |
| Calibration | a two point calibration renewalis recommended every 7 daysor 1 month if the same reagentlot is used and the reagent packis consumed within 7 days | a full calibration curve run isrecommended every 2 weeks |
Performance Characteristics:
| Feature | Elecsys T3 | Enzymun-Test® T3 | ||||||
|---|---|---|---|---|---|---|---|---|
| Precision: | NCCLS (modified) (EP5-T2): | Modified NCCLS “Midi” (EP3-T) | ||||||
| Sample | PC U1 | PC U2 | HS1 | HS2 | HS3 | 1 | 2 | 3 |
| N | 60 | 60 | 60 | 60 | 60 | 118 | 120 | 117 |
| Mean (nmol/l) | 2.12 | 6.31 | 1.22 | 2.87 | 5.09 | 0.95 | 2.56 | 4.26 |
| wi/in run % CV | 4.1 | 3.5 | 3.6 | 4.2 | 5.3 | 2.9 | 1.6 | 1.7 |
| total run % CV | 4.8 | 4.1 | 5.4 | 4.7 | 5.4 | 4.7 | 2.2 | 2.8 |
| Sensitivity | Lower Detection Limit:0.3 nmol/l0.19 ng/ml | Lower Detection Limit:0.46 nmol/l0.3 ng/ml | ||||||
| Assay range(LDL to high std.) | 0.3 - 10.00 nmol/l0.19 - 6.51 ng/ml | 0.46 - 9.22 nmol/l0.3 - 6.0 ng/ml |
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T
510(k) Summary, Continued
Performance Characteristics: F. Substantial
equivalence,
(cont.)
| MethodComparison | vs. Enzymun-Test T3 (Cat. # 1360868)Least Squares:N = 300$y = -0.35 + 1.18x$r = 0.957 | vs. Enzymun-Test T3 (Cat. # 1135287)Least Squares:N = 55$y = 1.13x + 0.02$r = 0.994 |
|---|---|---|
| Passing/BablokN = 300$y = -0.56 + 1.26x$r = 0.957 | ||
| Interfering | No interference up to: | No interference up to: |
| substance:HemoglobinLipemiaBilirubinBiotin | 1 g/dl1500 mg/dl25 mg/dl20 ng/ml | 1 g/dl1250 mg/dl65 mg/dl50 ng/ml |
| Specificity | % cross reaction | % cross reaction |
| D-T3L-T4D-T4L-rT3L-T2 | 98.90.1150.1150.0070.998 | 1000.160.070.041.0 |
| 3,3',5-tri-iodothyroacetic acid3,3',5,5'-tetra-iodothyroacetic acid | 106.40.007 | 7.50.01 |
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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized image of a human figure embracing a bird, which is a symbol of care and protection.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
AUG 1 5 1996
LeeAnn Chambers, RAC Program Manager, Regulatory Affairs Boehringer Mannheim Corporation Quality System & Compliance 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457
Re : K962508 Elecsys T3 II Requlatory Class: Product Code: CDP, JIS Dated: July 25, 1996 Received: July 26, 1996
Dear Ms. Chambers:
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 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 provisions The general controls provisions of the Act 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 (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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification 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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Page 2
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 at (301) 443-6597.
Sincerely yours,
Steven Sutman
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
V
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510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________ Device Name: _________________________________________________________________________________________________________________________________________________________________ Indications for Use:
Triiodothyronine (T3) is the hormone principally responsible for the development of the effects of the thyroid hormones on the various target organs.
T3 (3,5,3' Triiodothyronine) is mainly formed extra-thyroidally, particularly in the liver, by enzymatic 5'-deiodination of T4. Accordingly, the T3 concentration in serum is more a reflection of the functional state of the peripheral tissue than the secretory performance of the thyroid gland.
A reduction in the conversion of T4 to T3 results in a fall in the T3 concentration. It occurs under the influence of medications such as propanolol, glucocorticoids or amiodarone and in severe non-thyroidal general diseases - "non-thyroidal illness" (NTI) - and is referred to as the "low T3 syndrome." Like T4, over 99% of T3 is bound to transport proteins, but its affinity to them is around 10-fold lower.1-3,7
The determination of T3 is utilized in the diagnosis of T3-hyperthyroidism, the detection of early stages of hyperthyroidism and for indicating a diagnosis of thyrotoxicosis factitia. 4-6
References
- Wheeler MH, Lazarus JH. Diseases of the Thyroid. Chapman and Hall Medical. London l Glasgow Weinheim New York Tokyo Melbourne Madras 1994;107-115.
- Pfannenstiel P, Saller B. Schilddrüsenkrankheiten Diagnose und Therapie. Berliner 2 Medizinische Verlagsanstalt GmbH 1995; 2:30-32,60-62.
- ﻟﻠﺴﺎ Fisher DA. Physiological variations in thyroid hormones physiological and pathophysiological considerations. Clinical Chemistry 1996;42:135-139.
Continued on next page
นบุ๊กวอ
1
പറവാക
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Ala Peitrs
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number 5962508
Prescription Use
(Per 21 CFR 801.109) ✓
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 862.1710 Total triiodothyronine test system.
(a)
Identification. A total triiodothyronine test system is a device intended to measure the hormone triiodothyronine in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases such as hyperthyroidism.(b)
Classification. Class II. This device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.