(122 days)
MAGLUMI 2000 HCG/S-HCG is an in vitro chemiluminescence immunoassay for the quantitative determination of total beta human chorionic gonadotropin (total ß-hCG) in human serum. The measurement of total ß-hCG is used as an aid in the early detection of pregnancy.
MAGLUMI 2000 HCG/B-HCG kit consists of the following reagents: Magnetic Microbeads- coated with anti-HCG monoclonal antibody, containing BSA, NaN3 (
The provided text describes the performance characteristics of the MAGLUMI 2000 HCG/ß-HCG device, an in vitro chemiluminescence immunoassay for the quantitative determination of total beta human chorionic gonadotropin (total ß-hCG) in human serum. This information is presented as part of a 510(k) summary submitted to the FDA. While the document outlines various analytical performance studies, it does not explicitly define acceptance criteria in a quantitative table or refer to a multi-reader multi-case (MRMC) comparative effectiveness study.
However, we can infer acceptance based on the reported performance results aligning with standard clinical laboratory expectations and the successful substantial equivalence determination by the FDA. The study focuses on analytical performance characteristics rather than diagnostic accuracy involving human interpretation of results.
Here's an attempt to structure the information based on your request, identifying what is and isn't available in the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of acceptance criteria. Instead, it describes performance characteristics and indicates compliance with CLSI guidelines. We can infer the "acceptance" derived from the presented data and the overall conclusion of substantial equivalence.
| Performance Characteristic | Acceptance Criteria (Inferred from CLSI/Clinical Practice) | Reported Device Performance |
|---|---|---|
| Precision | Within-Run CV%: Generally 0.99 for quantitative assays over measurement range. | R² = 0.9932 (between 1.134 and 4680 mIU/mL) |
| Detection Limit (LOB) | Determined by 95th percentile, should be clinically appropriate. | 0.302 mIU/mL (highest of 3 lots) |
| Detection Limit (LOD) | Clinically appropriate for early detection of pregnancy. | 0.471 mIU/mL (highest of 3 lots) |
| Limit of Quantitation (LOQ) | CV% no more than 20%, Bias no more than 15%. | 1.134 mIU/mL (highest of 3 lots) |
| Interference | Recovery ±10% of initial value for various interferents. | No significant interference observed at tested concentrations (details in text for TSH, LH, FSH, hGH, hCG α-subunit, bilirubin, hemoglobin, triglyceride, common drugs, HAMA, RF, total protein). |
| Hook Effect | No hook effect within clinically relevant high concentrations. | No HOOK effect observed within 1,000,000 mIU/mL. |
| Dilution Recovery | Percent differences for diluted specimen versus expected concentration within 10%. | Percent differences for diluted specimen versus expected concentration were within 10%. |
| Method Comparison | Strong correlation (high R²) and acceptable bias (slope near 1, intercept near 0) when compared to predicate device. | Y = 0.988X + 1.995, R² = 0.993 (All three sites) |
| Stability | Reagents/controls stable for specified period at specified conditions. | Accelerated stability showed 12 months at 2-8°C. Real-time stability is ongoing. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study: 80 samples analyzed per level (Control 1, Control 2, Control 3, Calibrator Low, Calibrator High, and 6 Native Serum Pools) on each of three instruments. Total N=240 samples per level across three instruments.
- Linearity Study: Linearity samples prepared by mixing high and low level samples. Each sample was measured in quadruple on 3 lots of reagent. The exact number of distinct linearity samples (different concentrations) is not specified, but the range is 0.3 to 4680 mIU/mL.
- Detection Limit Studies:
- LOB: 80 measurements of HCG/ß-HCG negative serum samples using 3 different lots over 5 days.
- LOD: Four levels of low samples, measured in 80 replicates over 5 days per sample using 3 lots of reagents.
- LOQ: Six low serum samples, in six replicates per run, one run per day, over 5 days, using 3 lots of reagents.
- Interference Study: Two base serum samples (6.0 mIU/mL and 100 mIU/mL HCG/ß-HCG) spiked with various cross-reactants. Also, human serum pools with 6.0 mIU/mL, 100 mIU/mL, and 2000 mIU/mL HCG/ß-HCG for endogenous substances and common drugs. Each tested using 3 lots of reagents. Exact number of distinct interferent samples not specified.
- Hook Effect: Six samples with HCG/ß-HCG concentrations from 5000 to 1,000,000 mIU/mL prepared by spiking. Serial dilutions tested using 3 different lots.
- On-board Dilution Recovery: Twelve serum samples with HCG/ß-HCG concentrations from 4475 to 223750 mIU/mL tested using three reagent lots and three instruments.
- Method Comparison Study: 201 human serum samples with concentrations ranging from 1.1 to 4934 mIU/mL (as determined by the predicate device).
- Expected Values/Reference Range: 431 serum samples from non-pregnant, apparently healthy females (20 years and older).
Data Provenance: The document does not explicitly state the country of origin for the data. Given the submitter's location (Shenzhen, China) and the FDA submission, it's likely the studies were conducted in China or involved samples from that region, but this is not explicitly confirmed. The studies are described in a manner typical of prospective performance evaluation studies for an in vitro diagnostic device, rather than retrospective analysis of pre-existing data.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable to this submission. The device is an in vitro diagnostic immunoassay for quantitative measurement of a biomarker (hCG). Ground truth is established by the reference measurement procedure of the MAGLUMI 2000 instrument itself and validated through analytical performance studies (precision, linearity, detection limits, method comparison to a legally marketed predicate device, etc.) rather than through expert human interpretation of images or clinical findings.
4. Adjudication Method for the Test Set
Not applicable. As the device is an in vitro diagnostic assay providing a quantitative numerical result, there is no human interpretation or subjective assessment that would require an adjudication method. The "ground truth" for method comparison is the value obtained from the predicate device. For analytical performance studies, it's the objectively measured values and their statistical distributions.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No. An MRMC study is typically conducted for image-based diagnostic aids (e.g., AI for radiology) where human readers interpret medical images. This device is a lab-based immunoassay that provides a quantitative numerical result. Therefore, an MRMC study is not relevant or applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the entire study is essentially a standalone performance evaluation. The MAGLUMI 2000 HCG/ß-HCG is an automated chemiluminescence immunoassay system. Its performance characteristics (precision, linearity, detection limits, interference, hook effect, dilution recovery, and method comparison) are evaluated as the direct output of the instrument and its reagents, without explicit human interpretation being part of the device's function or the primary subject of these studies. The quantitative output of the device itself constitutes its "performance."
7. The Type of Ground Truth Used
The ground truth for this device's performance evaluation is established through:
- Reference Measurement Procedures/Known Concentrations: For studies like linearity, detection limits, and interference, known concentrations or "spiked" samples are used as a reference.
- Measurement against a Predicate Device: For the method comparison study, the results from the Beckman Access Total B-HCG (5th IS) Assay (the predicate device) served as the comparative "ground truth" to establish substantial equivalence.
- Statistical Analysis of Replicate Measurements: For precision, the statistical variation around the mean measured value for controls and patient samples provides the "ground truth" of the device's reproducibility.
- Physiological/Clinical Samples: For determining expected values/reference ranges, samples from apparently healthy individuals are used.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of an algorithm or machine learning model. This is an in vitro diagnostic assay, not an AI/ML-based device that typically undergoes a distinct training/validation/test split of data. The studies described are analytical verification and validation studies in a traditional medical device development sense.
9. How the Ground Truth for the Training Set was Established
Not applicable. As there is no defined "training set" for an AI/ML algorithm, this question is not relevant to the described device and its evaluation. The "training" of such a system would involve the manufacturer's internal assay development and optimization, which isn't part of a regulatory submission summary like this.
§ 862.1155 Human chorionic gonadotropin (HCG) test system.
(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.