(77 days)
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No
The device description details a standard immunoassay technology with fluorescence detection and calculation based on a stored calibration curve. There is no mention of AI or ML in the intended use, device description, or performance studies.
No.
The device is for the quantitative determination of human chorionic gonadotropin (hCG) in serum for the early detection of pregnancy and diagnostic purposes. It is not designed to treat, prevent, or mitigate any disease or condition.
Yes
Explanation: The device is used for the "quantitative determination of human chorionic gonadotropin (hCG) in serum for the early detection of pregnancy" and can "aid in the determination of ectopic pregnancy and spontaneous abortion". These are diagnostic purposes.
No
The device description clearly outlines a physical instrument (IOS™ instrument) that interacts with physical test cartridges (IOS™ Quantitative hCG Test Cartridges) and controls (IOS™ Immunoassay Controls Kit) to perform a chemical immunoassay and measure a fluorescent signal. This involves hardware components for sample handling, incubation, washing, and fluorescence detection, making it a hardware-based medical device with associated software for control and data processing.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "for the quantitative determination of human chorionic gonadotropin (hCG) in serum for the early detection of pregnancy." This is a diagnostic test performed on a biological sample (serum) to provide information about a patient's health status (pregnancy).
- Device Description: The description details a "two-site sandwich immunoassay" which is a common method used in in vitro diagnostic tests to detect and quantify specific substances in biological samples.
- Sample Type: The test is performed on "serum," which is a biological sample taken from a patient.
- Care Setting: The intended use specifies "clinical laboratories, physicians' office laboratories, and other alternate sites of use close to the point of patient care," which are typical settings where IVD tests are performed.
- Performance Studies: The document describes performance studies using "patient samples," further indicating its use in a diagnostic context.
The device fits the definition of an In Vitro Diagnostic device as it is intended for use in the examination of specimens derived from the human body to provide information for diagnostic purposes.
N/A
Intended Use / Indications for Use
The IOS™ Quantitative hCG Test Cartridges are to be used for the quantitative determination of human chorionic gonadotropin (hCG) in serum for the early detection of pregnancy. They are intended to be used with the IOS™ instrument in clinical laboratories, physicians' office laboratories, and other alternate sites of use close to the point of patient care.
The IOS™ Immunoassay Controls Kit is to be used to assist in monitoring accuracy and precision in the IOS™ immunoassay test cartridges.
Product codes (comma separated list FDA assigned to the subject device)
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Device Description
Quantitative hCG Test Cartridges: Human chorionic gonadotropin is a glycoprotein that is synthesized by the placenta during pregnancy and appears in both serum and urine relatively soon after implantation of the developing embryo. The presence of hCG, and its rapid rise following conception, is thus the basis of pregnancy testing. (1) Quantitation of hCG can aid in the determination of ectopic pregnancy and spontaneous abortion (2, 3). hCG is also secreted by a wide variety of tumors: gestational trophoblastic tumors, testicular and prostatic tumors, and some breast cancers. (4,5).
Human chorionic gonadotropin is composed of two noncovalently linked polypeptides: the alpha and beta subunits. The individual subunits lack biological activity, but become active when combined to form the intact hormone. The alpha subunit of hCG is structurally homologous to the alpha subunits of LH (luteinizing hormone), FSH (follicle stimulating hormone), and TSH (thyroid stimulating hormone). The beta subunit of each of the hormones is structurally unique and confers the biologic and immunologic specificity to each hormone. The beta subunit of hCG contains a unique chain of 30 carboxy-terminal amino acids that confers its specificity (1). Monoclonal antibodies directed against this portion of the beta subunit permit differentiation between hCG and the other pituitary glycoprotein hormones.
Principle of the Test:
Quantitative hCG Test Cartridges: The IOS™ Quantitative hCG test is a two-site sandwich immunoassay which utilizes two antibodies directed against hCG: a polyclonal antibody immobilized on the plastic cartridge surface (capture antibody) and a monoclonal antibody labeled with alkaline phosphatase (detection antibody, conjugate). hCG in the patient sample binds to conjugate in the test cartridge, and this hCG-conjugate complex then binds to the immobilized capture antibody. After a short incubation period, unbound hCG-conjugate complex is washed away. Substrate is added, which reacts with the alkaline phosphatase conjugate-hCG-capture antibody 'sandwich' and produces a fluorescent signal. The level of fluorescence is directly proportional to the amount of bound hCG-conjugate, which is directly proportional to the amount of hCG present in the patient sample. All reagents necessary to perform the test are dried in the IOS™ 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™ Quantitative hCG cartridge in the IOS™ instrument. When prompted, the operator adds sample well. A second portion of patient sample is diluted off-line, using the dilution vial supplied with the kit, and pipetted into the second well of the test cartridge. The operator starts the test sequence when sample addition is complete. Patient sample rehydrates conjugate dried in the sample well; the conjugate binds to hCG present in the patient serum sample. This hCG-conjugate complex then flows into the incubation/reaction chamber where it binds to the immobilized capture antibody. At the end of the incubation time, unbound sample-conjugate is washed away by buffer. Buffer is used to rehydrate the dried substrate necessary for signal generation and quantitation of hCG, and the rehydrated substrate is then delivered to 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 the instrument memory, and the amount of hCG present in the patient sample is calculated from the stored calibration curve. If the signal from the first track (undiluted patient serum) is higher than that of the highest calibrator, the instrument will take a reading from the second track (user-diluted sample) to obtain a quantitative value for the patient sample. This increases the assay range 2500 mIU/mL (undiluted track) to 250,000 mIU/mL (diluted track).
Immunoassay 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. The Biocircuits IOS™ Immunoassay Controls are two levels of bloodbased material for use with Biocircuits IOS™ Test Cartridges.
To run a control, the operator inserts the 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.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
clinical laboratories, physicians' office laboratories, and other alternate sites of use close to the point of patient care.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-clinical testing:
Precision: Control Level 1: Mean 36.8 mIU/mL, SD 4.26, %CV within-day 8.88, %CV between-day 10.89, %CV total 11.57.
Control Level 2: Mean 169.2 mIU/mL, SD 16.39, %CV within-day 8.35, %CV between-day 9.06, %CV total 9.69.
Control Level 3: Mean 339.3 mIU/mL, SD 34.46, %CV within-day 5.76, %CV between-day 10.75, %CV total 10.16.
Accuracy: Comparison of methods using 165 patient samples (2 mIU/mL to 2270 mIU/mL neat sera, n=107) gave a correlation coefficient (r) of 0.981 with y = 5.63 + 0.89x. Diluted samples up to 181,000 mIU/mL (n=58) resulted in a correlation coefficient of 0.986 and y = 0.002 + 0.955x for the entire range.
Clinical testing (physicians' office laboratories):
Precision: Control Level 1: Number of replicates 39, Mean 35.34 mIU/mL, SD 4.08, %CV total 11.54.
Control Level 2: Number of replicates 31, Mean 152.79 mIU/mL, SD 13.72, %CV total 8.98.
Accuracy: Comparison of methods using 121 patient samples (2.0 mIU/mL to 202,598 mIU/mL) tested in three typical physicians' office laboratories and retested at the manufacturer's lab on the predicate device. This gave a correlation coefficient (r) of 0.996 with y = 0.002 + 0.880x.
Immunoassay Controls: Ranges established for Control Level 1 (T4: Mean 8.1 ug/dL, Range 6.48-9.72; T-Uptake: Mean 32.4%, Range 29.25-35.55) and Control Level 2 (T4: Mean 12.9 ug/dL, Range 10.32-15.4; T-Uptake: Mean 39.7%, Range 36.85-42.55). These ranges were determined over several days using several IOS™ instruments, with at least 40 cartridges tested for each control level to establish the ranges for the specific lot.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
The IOS Quantitative hCG Test Cartridges are substantially equivalent to the Dade Stratus Fluorometric Enzyme hCG Immunoassay currently manufactured and distributed by Dade International.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.
0
DEC - 5 1996
Attachment B
Revised Summary of Information Respecting Safety and Effectiveness
Biocircuits IOS™ Quantitative hCG Test Cartridges and IOS™ Immunoassay Controls
1
510(k) Summary of Information Respecting Safety and Effectiveness
- A. Submitter: Biocircuits Corporation 1324 Chesapeake Terrace Sunnyvale, CA 94089 (408) 745-1961 Contact: Sheila Ramerman Date Prepared: November 1, 1996
- Device Names: B. Biocircuits IOS™ Quantitative hCG Test Cartridges Proprietary Name: Biocircuits IOS™ Immunoassay Controls (formerly IOS™ Thyroid Controls) Reagents for hCG (human chorionic gonadotropin) Common Names: Quality control materials (assayed and unassayed) human chorionic gonadotropin (hCG) test system Classification Name: Quality control materials (assayed and unassayed)
C. Legally Marketed Device:
The IOS Quantitative hCG Test Cartridges are substantially equivalent to the Dade Stratus Fluorometric Enzyme hCG Immunoassay currently manufactured and distributed by Dade International.
Device Description: D.
Quantitative hCG Test Cartridges: Human chorionic gonadotropin is a glycoprotein that is synthesized by the placenta during pregnancy and appears in both serum and urine relatively soon after implantation of the developing embryo. The presence of hCG, and its rapid rise following conception, is thus the basis of pregnancy testing. (1) Quantitation of hCG can aid in the determination of ectopic pregnancy and spontaneous abortion (2, 3). hCG is also secreted by a wide variety of tumors: gestational trophoblastic tumors, testicular and prostatic tumors, and some breast cancers. (4,5).
Human chorionic gonadotropin is composed of two noncovalently linked polypeptides: the alpha and beta subunits. The individual subunits lack biological activity, but become active when combined to form the intact hormone. The alpha subunit of hCG is structurally homologous to the alpha subunits of LH (luteinizing hormone), FSH (follicle stimulating hormone), and TSH (thyroid stimulating hormone). The beta subunit of each of the hormones is structurally unique and confers the biologic and immunologic specificity to each hormone. The beta subunit of hCG contains a unique chain of 30 carboxy-terminal amino acids that confers its specificity (1). Monoclonal antibodies directed against this portion of the beta subunit permit differentiation between hCG and the other pituitary glycoprotein hormones.
2
Principle of the Test
Quantitative hCG Test Cartridges: The IOS™ Quantitative hCG test is a two-site sandwich immunoassay which utilizes two antibodies directed against hCG: a polyclonal antibody immobilized on the plastic cartridge surface (capture antibody) and a monoclonal antibody labeled with alkaline phosphatase (detection antibody, conjugate). hCG in the patient sample binds to conjugate in the test cartridge, and this hCG-conjugate complex then binds to the immobilized capture antibody. After a short incubation period, unbound hCG-conjugate complex is washed away. Substrate is added, which reacts with the alkaline phosphatase conjugate-hCG-capture antibody 'sandwich' and produces a fluorescent signal. The level of fluorescence is directly proportional to the amount of bound hCG-conjugate, which is directly proportional to the amount of hCG present in the patient sample. All reagents necessary to perform the test are dried in the IOS™ 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™ Quantitative hCG cartridge in the IOS™ instrument. When prompted, the operator adds sample well. A second portion of patient sample is diluted off-line, using the dilution vial supplied with the kit, and pipetted into the second well of the test cartridge. The operator starts the test sequence when sample addition is complete. Patient sample rehydrates conjugate dried in the sample well; the conjugate binds to hCG present in the patient serum sample. This hCG-conjugate complex then flows into the incubation/reaction chamber where it binds to the immobilized capture antibody. At the end of the incubation time, unbound sample-conjugate is washed away by buffer. Buffer is used to rehydrate the dried substrate necessary for signal generation and quantitation of hCG, and the rehydrated substrate is then delivered to 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 the instrument memory, and the amount of hCG present in the patient sample is calculated from the stored calibration curve. If the signal from the first track (undiluted patient serum) is higher than that of the highest calibrator, the instrument will take a reading from the second track (user-diluted sample) to obtain a quantitative value for the patient sample. This increases the assay range 2500 mIU/mL (undiluted track) to 250,000 mIU/mL (diluted track).
Immunoassay 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. The Biocircuits IOS™ Immunoassay Controls are two levels of bloodbased material for use with Biocircuits IOS™ Test Cartridges.
To run a control, the operator inserts the 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.
- E. Intended Use:
The IOS™ Quantitative hCG Test Cartridges are to be used for the quantitative determination of human chorionic gonadotropin (hCG) in serum for the early detection of pregnancy. They are intended to be used with the IOS™ instrument in clinical laboratories, physicians' office laboratories, and other alternate sites of use close to the point of patient care.
AA
3
The IOS™ Immunoassay Controls Kit is to be used to assist in monitoring accuracy and precision in the IOS™ immunoassay test cartridges.
Comparison with the Predicate Device: F.
Table I summarizes the comparative features of the IOS and Stratus assays.
G. Performance Data:
Quantitative hCG Test Cartridges:
Non-clinical testing performed in the manufacturer's laboratories gave the following results:
| Control Level | 1 | 2 | 3 | |
|---|---|---|---|---|
| Mean, overall (mIU/mL) | 36.8 | 169.2 | 339.3 | |
| SD, overall (mIU/mL) | 4.26 | 16.39 | 34.46 | |
| % CV, within-day (n ≥ 19) | 8.88 | 8.35 | 5.76 | |
| % CV, between-day (n ≥ 60) | 10.89 | 9.06 | 10.75 | |
| % CV, total | 11.57 | 9.69 | 10.16 |
- Accuracy: A comparison of methods was performed by testing a total of 165 patient samples in the manufacturer's laboratories using the IOS™ Quantitative hCG carridges and a commercially available fluorescent enzyme immunoassay. Of the range of hCG concentration from 2 mIU/mL to 2270 mIU/mL (neat sera), 107 samples tested gave a correlation coefficient (r) of 0.981 with the line of regression described by the equation y = 5.63 + 0.89x. Diluted samples with hCG concentrations up to 181,000 mIU/mL (n = 58) were also tested in the study, giving a correlation coefficient of 0.986 and a line of regression of y = 0.002 + 0.955x for the entire range of samples tested (2 - 181,000 mIU/mL hCG).
Clinical testing performed in typical physicians' office laboratories gave the following results:
Precision: l.
| Control Level | 1 | 2 |
|---|---|---|
| Number of replicates | 39 | 31 |
| Mean (mIU/mL) | 35.34 | 152.79 |
| SD, overall (mIU/mL) | 4.08 | 13.72 |
| % CV, total | 11.54 | 8.98 |
Accuracy: A comparison of methods was performed by users in three typical 2. physicians' office laboratories. Sites of testing included an OB/GYN practice, an Internal Medicine practice, and a Reproductive EndocrinologyFerrility practice. Users included medical technologists, medical assistants, and front-office personnel. A total of 121 patient samples were tested using the IOS™ Quantitative hCG carridges in the office laboratories; the samples were split and sent to the manufacturer's laboratory for retesting on the predicate device. These studies gave a correlation coefficient (r) of 0.996 with the line of regression described by the equation y = 0.002 + 0.880x. Samples tested ranged from 2.0 mIU/mL to 202,598 mIU/mL, and included diluted samples.
4
Immunoassay Controls
The following ranges for the IOS™ Immunoassay Controls were determined in studies in the manufacturer's laboratories. To establish the ranges, the controls were tested in at least 40 cartridges each, over several days, using several IOS™ instruments. These values only apply to this lot of IOSTM Immunoassay Controls. Different lots of Immunoassay Controls will likely have slightly different ranges. Your laboratory should establish its own range for these controls over time.
| Analyte | Control Level 1 | Control Level 2 | ||
|---|---|---|---|---|
| Mean | Range | Mean | Range | |
| T4 (ug/dL) | 8.1 | 6.48-9.72 | 12.9 | 10.32-15.4 |
| T-Uptake (%) | 32.4 | 29.25-35.55 | 39.7 | 36.85-42.55 |
| hCG (mIU/mL) |
It is self-evident from the data and information presented here that the Biocircuits IOS™ Quantitative hCG Test Cartridges are as safe, effective, and perform as well as the Dade Stratus hCG Fluorometric Immunoassay manufactured and distributed by Dade International.
Attachment: Table I: Assay Comparison
5
Dade STRATUS vs. Biocircuits IOS™
Dade STRATUS vs. Biocircuits IOS™
Assay Comparison
| ATTRIBUTE | STRATUS hCG | IOS™ hCG | |
|---|---|---|---|
| Technology | Fluorometric enzyme immunoassay | Fluorometric Enzyme immunoassay | |
| Assay format | Sandwich (two-site) | Sandwich (two-site) | |
| Enzyme label | Alkaline phosphatase | Alkaline phosphatase | |
| Substrate | Methylumbelliferyl phosphate | Methylumbelliferyl phosphate | |
| Reagents | Immobilization Medium | ||
| Dry | Reaction tab | ||
| Monoclonal antibody only | Plastic cartridge | ||
| Polyclonal antibody, monoclonal antibody- | |||
| conjugate, substrate | |||
| Wet | 2 (assay-specific), loaded by operator at start | ||
| of each run | 1(used for all assays), continuously on board | ||
| Delivery | Fully automated | Fully automated | |
| Calibration | Calibration | User-generated | Factory-generated |
| Calibration Stability | 14 days (minimum) | 90 days (minimum) | |
| Storage | Refrigerated (2-8°C) | Room Temperature (15-30°C) | |
| Sample | Type | Serum or plasma | Serum |
| Volume | 0.2 ml (minimum) | 0.1 mL | |
| Measurement Needed | Non-precision | Non-precision | |
| Dilution | Manual or programmable | Manual, run at same time as undiluted sera | |
| Operating environment | 22°-32° C | 15°-30° C | |
| Data analysis | Microprocessor-controlled | ||
| Stored standard curves | Microprocessor-controlled | ||
| Stored standard curves | |||
| Data output | LCD display | ||
| Printed alphanumeric hard copy | LCD display | ||
| Printed alphanumeric hard copy |
Ay