FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

AFIAS TSH-SP, for use in conjunction with the AFIAS-6/SP Analyzer, is an immunofluorometric test system intended for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites for the quantitative measurement of thyroid stimulating hormone (TSH) levels in serum, sodium-heparinized plasma samples. The test system is intended for use as an aid in the diagnosis of thyroid or pituitary disorders.

AFIAS-6/SP Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Pointof-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in serum or plasma samples.

AFIAS TSH-VB, for use in conjunction with the AFIAS-6/VB Analyzer, is an immunofluorometric test system intended for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites for the quantitative measurement of thyroid stimulating hormone (TSH) levels in sodium-heparinized or EDTA venous whole blood samples. The test system is intended for the monitoring of TSH levels in euthyroid and hypothyroid individuals.

AFIAS-6/VB Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Pointof-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in venous whole blood samples.

Device Description

AFIAS TSH-SP as well as AFIAS TSH-VB Test Cartridge is a plastic structure molded in the form of a disposable, self-contained, unitized device which houses the 'lyophilized detection buffer', the 'diluent i.e. reconstitution buffer' as well as the 'test strip'; all of which are integral components of the test. The test cartridge is an elongated structure having 140 mm length. 17 mm width and 17 mm height.

'AFIAS TSH-SP ID Chip' as well as 'AFIAS TSH-VB ID Chip' is a flat, rectangular device with its main body measuring 24 mm × 20 mm × 3 mm. Another rectangular portion measuring 12 mm × 10 mm × 2 mm protrudes out from the apical side of the main body. The ID Chip is an electronic memory device fitted into a plastic matrix. Lot-specific 'ID Chip' is an integral component of the test.

AFIAS-6/SP as well as AFIAS-6/VB analyzer is a compact, bench-top, automated, fluorometric analyzer measuring 42 cm (L) x 33.6 cm (W) x 29.3 cm (H). AFIAS-6 weighs 15.1 kg. Either analyzer is a flourometer instrument of closed-system analyzer type.

AI/ML Overview

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the AFIAS TSH devices:

Acceptance Criteria and Device Performance for AFIAS TSH-SP and AFIAS TSH-VB

Note: The document presents acceptance criteria implicitly through performance study results and comparisons to a predicate device. Specific numerical acceptance criteria (e.g., "CV must be 0.95 or higher). | 0.9998 (Serum vs. Sodium heparin plasma), 0.9997 (Serum vs. Di-Potassium EDTA plasma) | 0.9998 (Sodium heparin venous whole blood vs. Di-Potassium EDTA venous whole blood) |
| Clinical Method Comparison (Correlation Coefficient) | High correlation (e.g., >0.95 or higher) with predicate device. | 0.9994 | 0.9999 |
| Clinical Method Comparison (Weighted Deming Regression Slope) | Close to 1 (e.g., 0.9-1.1) to indicate agreement with predicate. | 0.976 | 0.909 |
| Clinical Method Comparison (Weighted Deming Regression Y-intercept) | Close to 0 to indicate agreement with predicate. | -0.003 | 0.012 |

2. Sample Size and Data Provenance

Limit of Blank (LoB):
- Test Set Sample Size: 5 unique blank/TSH-depleted human serum samples (for TSH-SP) and 5 unique blank/TSH-depleted whole blood samples (for TSH-VB). Each tested in 5 replicates, with 3 lots on 3 analyzers for 3 days, leading to 75 replicates per lot/analyzer.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-depleted).
Limit of Detection (LoD):
- Test Set Sample Size: 5 unique low TSH-spiked human serum samples (for TSH-SP) and 5 unique low TSH-spiked whole blood samples (for TSH-VB). Each tested in 5 replicates, with 3 lots on 3 analyzers for 3 days, leading to 75 replicates per lot/analyzer.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-spiked).
Limit of Quantitation (LoQ):
- Test Set Sample Size:
  - TSH-SP: 5 low TSH-spiked serum samples, tested in 2 replicates daily in two runs, for 21 successive days (total 210 measurements per sample per lot/analyzer combination).
  - TSH-VB: 4 low TSH-spiked venous whole blood samples, tested in 5 replicates daily in two runs, for 5 successive days (total 200 measurements per sample per lot/analyzer combination).
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-spiked).
Linearity and Reportable Range:
- Test Set Sample Size: 22 test samples each for TSH-SP (serum) and TSH-VB (whole blood), prepared by mixing high and TSH-depleted samples. Each tested in triplicate.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Susceptibility to High-dose Hook Effect:
- Test Set Sample Size: 12 spiked samples (TSH concentrations 25 to 3000 µIU/ml). Tested in triplicate.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Analytical Specificity:
- Test Set Sample Size: Samples spiked with various interferants/cross-reactants. Specific number of samples not detailed, but substances and concentrations are listed.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Site-to-Site Precision/Reproducibility:
- Test Set Sample Size:
  - TSH-SP: 4 serum samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml). Each tested in 5 replicates, with 3 lots on 3 analyzers (1 per site) by 9 operators (3 per site). Total 15 replicates per sample per site, 45 replicates per sample combined.
  - TSH-VB: 4 whole blood samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml). Each tested in 5 replicates, with 3 lots on 3 analyzers (1 per site) by 9 operators (3 per site). Total 15 replicates per sample per site, 45 replicates per sample combined.
- Data Provenance: External point-of-care sites. Not explicitly stated (e.g., country). Uses clinical samples (Clinical Serum Sample 1, 2, Clinical Venous Whole Blood Sample 1, 2) and spiked samples (Spiked Serum Sample 3, 4, Spiked Venous Whole Blood Sample 3, 4).
Matrix Comparison:
- Test Set Sample Size:
  - TSH-SP: 81 matched serum vs. sodium heparin plasma samples; 79 matched serum vs. Di-Potassium EDTA plasma samples.
  - TSH-VB: 63 matched sodium heparin venous whole blood vs. Di-Potassium EDTA venous whole blood samples.
- Data Provenance: Clinical samples from same study subjects. Not explicitly stated (e.g., country).
Adult Reference Interval:
- Test Set Sample Size:
  - TSH-SP: 128 apparently healthy adults (65 males, 63 females, age 21-70 years) for serum samples.
  - TSH-VB: 133 apparently healthy adults (69 males, 64 females, age 21-70 years) for sodium heparin venous whole blood samples.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be prospective collection of healthy adult samples.
Clinical Method Comparison:
- Test Set Sample Size:
  - TSH-SP: 183 serum samples (including 22 spiked).
  - TSH-VB: 157 sodium heparinized venous whole blood samples (including 22 spiked).
- Data Provenance: Clinical sites (three point-of-care sites). Samples collected from across the three study sites. Not explicitly stated (e.g., country).

3. Number of Experts and Qualifications for Ground Truth

The document describes in vitro diagnostic devices for measuring TSH levels. The performance studies for these types of devices primarily rely on established analytical methods and reference standards rather than expert human interpretation of images or clinical cases.
No "experts" were used to establish ground truth in the typical sense of a diagnostic imaging study (e.g., radiologists interpreting images). Instead, ground truth is established by:
- Reference testing (e.g., predicate device, or other established laboratory methods) for method comparison studies.
- Known concentrations for spiked samples (LoD, LoQ, Linearity, Hook Effect, Analytical Specificity).
- Large cohorts of 'apparently healthy adults' for reference intervals.

4. Adjudication Method

None specified. For in vitro diagnostic assays, ground truth is typically analytical (known concentrations, reference method results) rather than requiring adjudication of human interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is an in vitro diagnostic (IVD) test, not an imaging device that requires human interpretation. Therefore, an MRMC study comparing human readers with and without AI assistance is not applicable. The precision study did involve multiple operators at POC sites using the device, but this is different from an MRMC study for diagnostic interpretation.

6. Standalone Performance Study

Yes. All the analytical and clinical studies described (LoB, LoD, LoQ, Linearity, Hook Effect, Analytical Specificity, Site-to-Site Precision, Matrix Comparison, and Reference Interval determination) assess the algorithm/device performance in a standalone manner. The "human-in-the-loop" aspect is limited to the operator performing the test according to instructions, not interpreting results in a diagnostic imaging sense.
The Clinical Method Comparison study also implicitly evaluates standalone performance by comparing the device's results to a predicate device.

7. Type of Ground Truth Used

Known concentrations: For LoB, LoD, LoQ, Linearity, Hook Effect, and Analytical Specificity, ground truth is established by preparing samples with known or precisely characterized TSH concentrations (e.g., TSH-depleted, TSH-spiked samples).
Predicate device results: For Clinical Method Comparison, the results from the Access Fast hTSH (on the Access 2 system) are used as the reference/ground truth for comparison.
Statistically derived from healthy population: For Adult Reference Interval determination, ground truth is derived from the statistical distribution (2.5th and 97.5th percentiles) of TSH levels in a large cohort of apparently healthy adults.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning or AI models, as this is an IVD device and the performance studies focus on analytical validation.
However, the calibration process for the device (Lot-specific master calibration curve encoded in an ID chip) implies that a set of characterized samples would have been used by the manufacturer to establish these curves. The size of this internal calibration data set is not provided in this document.

9. How the Ground Truth for the Training Set Was Established

As above, due to this being an IVD device and not an AI/ML model with a distinct "training set" in the conventional sense, this information is not explicitly provided.
The calibration curves provided on the ID chips would have been established by the manufacturer using a reference method and a range of TSH standards/samples with known concentrations. This would involve a comprehensive analytical process to ensure accuracy and precision across the measuring range.

Summary

Regulation Number and Section

§ 862.1690 Thyroid stimulating hormone test system.

(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.