(209 days)
TSH: The IOS™ TSH Test Cartridge is to be used for the quantitative determination of thyroid stimulating hormone (TSH, thyrotropin) levels in serum using the Biocircuits IOS™ system.
Thyroid Controls: The IOS™ Thyroid Controls Kit is to be used to assist in monitoring accuracy and precision in the IOS™ thyroid assays.
Thyroid stimulating hormone (TSH) is a glycoprotein with a molecular weight of about 28,000 daltons that is secreted by the anterior pituitary gland. TSH interacts with a specific receptor on the thyroid gland cell surface, stimulating production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Secretion of TSH is regulated by two factors: 1) a hormone secreted by the hypothalamus called thyrotropin releasing hormone (TRH) which stimulates the pituitary to produce and release TSH; and 2) the concentration of unbound thyroid hormones T4 and T3 in the interstitial fluid of the brain. An increase of the concentrations of T4 and T3 inhibits the production and secretion of TSH, while a decrease in T4 and T3 levels stimulates production and secretion of TSH, forming a negative feedback mechanism. Failure at any level of regulation of the hypothalamic-pituitary-thyroid axis will result in either under-production (hypothyroidism) or over-production (hyperthyroidism) of T4 and/or T3.
Primary hypothyroidism is associated with low thyroid hormone levels and elevated TSH levels, while secondary (pituitary) and tertiary (hypothalamic) forms of hypothyroidism are associated with both low levels of T4 and/or T3 and low-to-undetectable levels of TSH. All three forms of hypothyroidism can be differentiated by the patient's TSH response to TRH.
Primary hyperthyroidism is associated with high levels of thyroid hormones and very low or undetectable levels of TSH. The TRH challenge test has been used to confirm primary hyperthyroidism. More recently, sensitive TSH assays have been developed which can differentiate overtly thyrotoxic patients from euthyroid individuals.
TSH is composed of two noncovalently linked subunits, designated "alpha" and "beta". The alpha portion is essentially identical to the alpha subunits of human luteinizing hormone (hLH), human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG), differing only in carbohydrate moieties. The beta subunits of each of these hormones is structurally unique and contains the biologic and immunologic specificity. Both subunits are needed for biological activity.
The Biocircuits IOS™ TSH assay uses a monoclonal antibody against the beta subunit of TSH to specifically capture the patient TSH, and a polyclonal antibody also against the beta subunit for the enzyme conjugate. This allows specific determination of the concentration of TSH without cross-reactivity with other glycoprotein hormones.
Principle of the Test:
TSH: The IOS™ TSH test is a two-site sandwich immunoassay. TSH in the patient sample binds to monoclonal anti-TSH antibody in the test cartridge. After a short incubation time, excess sample is washed away and enzyme-labeled polyclonal anti-TSH antibody (conjugate) is added, which binds to any antibody-bound TSH, forming an antibody-antigen-labeled antibody sandwich. After another short incubation time, excess conjugate is washed away and substrate is added. The rate of the enzyme-substrate reaction is directly proportional to the amount of conjugate bound, which is directly proportional to the amount of TSH present in the patient sample. All reagents necessary to perform the test are dried in the IOSTM cartridge, and are rehydrated by the addition of patient sample by the operator, or by the addition of buffer by the instrument.
To perform a test, the operator inserts an IOS™ TSH cartridge into the IOS™ instrument. When prompted, the operator adds sample to the sample well and starts the test sequence. The instrument draws the cartridge inside to be incubated. Patient sample flows into the incubation/reaction chamber where patient TSH binds to anti-TSH antibody. At the end of the sample incubation time, excess patient sample is washed away using buffer added by the instrument. Buffer is also added by the instrument to rehydrate dried conjugate in a separate reagent chamber for the next step; the rehydrated conjugate is then allowed to enter the incubation/reaction chamber and bind to antibody-bound TSH. At the end of the conjugate incubation time, excess conjugate is washed away by buffer. Buffer is used to rehydrate the substrate necessary for signal generation and quantitation of TSH in a second reagent chamber; rehydrated substrate is then allowed to enter the incubation/reaction chamber. The fluorescent signal produced is read as a rate by front-surface fluorometry, compared to the rates produced by a series of calibrators stored in instrument memory, and the amount of TSH present in the patient sample is calculated from the stored calibration curve.
Thyroid Controls: The use of materials derived from human blood to monitor quality control of clinical chemistry testing in the clinical laboratory has been widely established over the past several years. (1) The Biocircuits IOS™ Thyroid Controls are two levels of blood-based material for use with Biocircuits IOSTM thyroid assays test cartridges (T4/TU, T4, or TSH),
To run a control, the operator inserts the Thyroid Control Cartridge (packaged with the controls) into the IOS™ instrument. The instrument reads the lot number and ranges of acceptable values for the control solutions from the Control Cartridge barcode, and then ejects the Control Cartridge. The operator then inserts a test cartridge and follows the instrument prompts to identify the control level, apply control solutions, and begin the test sequence. The IOS™ instrument performs the required buffer additions to rehydrate assay reagents and perform wash steps as necessary, reads the fluorescence signal generated, and calculates and prints the control result just as it would if the cartridge were used to test a patient sample.
This looks like a 510(k) premarket notification for a TSH assay rather than an AI/ML powered device. While it contains performance data and a comparison to a predicate device, it does not involve the typical elements of an AI/ML study such as training sets, ground truth establishment by experts, or MRMC comparative effectiveness studies. Therefore, many of the requested fields cannot be filled.
Here's an analysis based on the provided text, focusing on the available information:
Acceptance Criteria and Device Performance for Biocircuits IOS™ TSH Test Cartridges
Device Name: Biocircuits IOS™ TSH Test Cartridges
Predicate Device: Stratus ultra-sensitive hTSH test (Dade International)
Intended Use: Quantitative determination of thyroid stimulating hormone (TSH, thyrotropin) levels in serum using the Biocircuits IOS™ system.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. Instead, the study aims to demonstrate substantial equivalence to the predicate device and acceptable precision and accuracy for diagnostic use. The reported performance is as follows:
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Biocircuits IOS™ TSH Assay) |
|---|---|---|
| Accuracy (Correlation with Predicate Device - Manufacturer Lab) | High correlation (e.g., r > 0.95) and regression line close to y=x when compared to a commercially available fluorescent enzyme immunoassay (implied predicate or well-established method). | Correlation coefficient (r): 0.98 |
| Line of regression: y = 0.141 + 1.07x | ||
| Sample Range: ≤ 0.173 uIU/mL to 26.30 uIU/mL | ||
| Accuracy (Correlation with Predicate Device - Physician's Office Lab) | High correlation (e.g., r > 0.95) and regression line close to y=x when compared to the predicate method. | Correlation coefficient (r): 0.978 |
| Line of regression: y = 0.255 + 0.922x | ||
| Sample Range: ≤ 0.173 uIU/mL to 23.06 uIU/mL | ||
| Precision (Manufacturer Lab - Within-day) | Acceptable within-day variability (e.g., %CV |
§ 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.