(289 days)
For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. The Elecsys HCG STAT immunoassay is intended for use in the early detection of pregnancy. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.
The Elecsys HCG STAT immunoassay makes use of a sandwich test principle using monoclonal antibodies specifically directed against Human Chorionic Gonadotropin (HCG). The antibodies labeled with ruthenium complex consist of a chimeric construct from human and mouse specific components. The Elecsys HCG STAT immunoassay is used for the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma. It is intended for use on the cobas e 601immunoassay analyzer.
The provided text describes the Elecsys HCG STAT immunoassay, its intended use, technological characteristics, and non-clinical performance evaluations conducted to demonstrate its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study information as requested:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly present a table of acceptance criteria with corresponding performance, but rather lists the performance data obtained and states that "All performance specifications were met." We can infer the acceptance criteria from the context of typical FDA 510(k) submissions for in vitro diagnostics, where equivalence to the predicate and meeting standard analytical performance metrics are key.
| Performance Metric | Acceptance Criteria (Implied / Stated) | Reported Device Performance |
|---|---|---|
| Intended Use | Same as predicate device (Elecsys HCG STAT, K002148) | For the in vitro quantitative determination of human chorionic gonadotropin (hCG) in human serum and plasma, for early detection of pregnancy, on the cobas e 601 immunoassay analyzer. (Same as predicate) |
| Assay Method | Same as predicate device | Sandwich Principle (Same as predicate) |
| Detection Method | Same as predicate device | Electrochemiluminescence (Same as predicate) |
| Applications/Test Time | Same as predicate device | 9 minutes (Same as predicate) |
| Instrument Platform | Functionality on cobas e 601 | cobas e 601 (Predicate includes cobas e 411, e 601, e 602, e 801. The updated device is specifically for e 601.) |
| Sample Type/Matrix | Same as predicate device | Human serum, plasma (Same as predicate) |
| Sample Anticoagulants | Same as predicate device | Li-heparin, K2-EDTA and K3-EDTA plasma (Same as predicate) |
| Calibrator | Same as predicate device | HCG STAT CalSet (Same as predicate) |
| Calibration Method | Same as predicate device | Traceability to 4th International Standard for Chorionic Gonadotropin (NIBSC code 75/589); master curve adapted with CalSet. (Same as predicate) |
| Calibration Interval | Same as predicate device | Once per reagent lot (extended based on verification); renewed after 1 month for same lot or 7 days for same kit. (Same as predicate) |
| Controls | Same as predicate device | Run individually at least once every 24 hours, once per reagent kit, after each calibration. (Same as predicate) |
| Traceability/Standardization | Same as predicate device | Standardized against 4th International Standard for Chorionic Gonadotropin (NIBSC code 75/589). (Same as predicate) |
| Reagent Stability | Same as predicate device | Unopened: 2-8 °C up to expiration date; After opening: 2-8 °C for 12 weeks; On analyzer: 4 weeks. (Same as predicate) |
| Measuring Range | Values within clinical requirements and comparable to predicate. | 1.0 - 10000 mIU/mL (Predicate: 0.500-10000 mIU/mL). Note: The lower limit shifted from 0.500 to 1.0 mIU/mL. The document does not explicitly state this as an issue for substantial equivalence, implying it falls within acceptable clinical utility for its indicated use. |
| Precision | Meet CLSI EP05-A3 guidelines. | Evaluated using CLSI EP05-A3, producing Repeatability and Intermediate precision (SD and CV values). Specific values are not provided in the summary but were generated. |
| LoB (Limit of Blank) | Meet CLSI EP17-A2 guidelines. | 0.5 mIU/mL (Predicate: 0.500 mIU/mL as lower detection limit) |
| LoD (Limit of Detection) | Meet CLSI EP17-A2 guidelines. | 1.0 mIU/mL (Predicate: 0.500 mIU/mL as lower detection limit) |
| LoQ (Limit of Quantitation) | Meet CLSI EP17-A2 and EP05-A3 guidelines. | 1.0 mIU/mL (Predicate: 0.500 mIU/mL as lower detection limit) |
| Analytical Specificity/Cross-Reactivity | Acceptable levels of cross-reactivity, comparable to predicate. | FSH 0.007 %, TSH 0.001 % (Predicate: FSH 0.09 %, TSH: no cross-reactivity). This indicates improved specificity for the updated device compared to the predicate's reported FSH cross-reactivity. |
| Biotin Interference | No significant interference at relevant concentrations, comparable to predicate. | No biotin interference in serum concentrations up to 1200 ng/mL (Predicate: ≤ 164 nmol/L or ≤ 40 ng/mL). This indicates a significantly higher tolerance to biotin for the updated device, which is an improvement. |
| Hook Effect | No Hook Effect up to a specified high concentration, comparable to predicate. | No Hook Effect up to ≥ 500,000 mIU/mL (Same as predicate) |
| Method Comparison (vs. Predicate) | Linear regression and Passing/Bablok analysis demonstrating strong correlation and agreement with the predicate device (slope near 1, intercept near 0, high R/T value). | Passing/Bablok: y= 1.012x-0.970, T = 0.996. Linear regression: y = 1.011x + 4.81, r = 1.000. (Predicate's comparison to HCG+ẞ: Passing/Bablok y = 1.0x - 7.38, T = 0.986; Linear regression y = 1.05x - 5.26, r = 0.999). The comparison shows high correlation and close agreement between the updated device and the predicate. |
| Stability | Meet predetermined stability claims (e.g., shelf-life, on-board stability) | Stability studies "reviewed and found to be acceptable," supporting claims in package labeling. (No specific values provided in summary). |
| Linearity | Meet CLSI EP6-A guidelines. | Data analysis determined according to CLSI EP6-A. (Specific data not provided in summary). |
| Endogenous Interferences | Recovery within acceptable limits for various interferents. | Effect on quantitation determined for hemoglobin, intralipid, bilirubin, rheumatoid factor by calculating recovery (absolute deviation or % recovery). (Specific data not provided in summary). |
| Common Drug Interferences | No significant interference for common pharmaceutical compounds. | Determined by comparing values of spiked samples with reference sample for 17 common pharmaceutical compounds. (Specific data not provided in summary). |
| Sample Matrix Comparison | Agreement between different anticoagulant plasma types and serum. | Assessed by Passing/Bablok regression analysis for serum vs. Li-Heparin, K2-EDTA, and K3-EDTA plasma. (Specific data not provided in summary). |
2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
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Precision (21-Day): Five human serum samples (HS1-HS5) and two controls (PreciControl Universal level 1 and 2). Replicated twice per run, two runs per day for 21 days (total 84 replicates per sample/control per lot). 1 lot used.
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Precision (5-Day): Five human serum samples (HS1-HS5) and two controls (PreciControl Universal level 1 and 2). 5 aliquots per run, 1 run per day for 5 days. 3 lots used.
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Reproducibility: Six human serum samples (HSP 1-6) and two controls (CTR 1-2). 5 replicates per run, 1 run per day. 1 lot used.
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LoB (Limit of Blank): Five analyte-free samples, measured in two-fold determinations in 6 runs over ≥ 3 days. 2 different lots. Total 60 measured values per lot.
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LoD (Limit of Detection): Five low-analyte concentration samples (from LoB up to approx. 4x LoB), measured in two-fold determinations in 6 runs over ≥ 3 days. 2 different lots. Total 60 measured values per lot.
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LoQ (Limit of Quantitation): 5 human serum samples covering the range between LoB and 2x LoQ. Measured in 5 replicates, one run per day over 5 days. 2 lots evaluated.
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Linearity/Assay Reportable Range: One human serum sample (high analyte), diluted through 21 steps. Assayed in 3-fold determinations. 1 lot tested.
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High Dose Hook Effect: Three human serum samples spiked with HCG. Dilution series performed. 1 reagent lot.
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Endogenous Interferences: One lot tested on 3 samples of each interfering substance (Hemoglobin, Intralipid, Bilirubin, Rheumatoid Factors). Each HCG sample (low, medium, high) spiked with interferent in 9 dilution steps.
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Biotin Interference: Three serum samples (low, medium, high HCG concentration) spiked with biotin up to 3600 ng/mL in 11 dilution steps.
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Common Drug Interferences: One human serum sample (HCG conc. near 5 mIU/mL and near 50 mIU/mL), spiked with 17 common pharmaceutical compounds.
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Analytical Specificity/Cross-Reactivity: One human serum matrix with HCG level (5 mIU/mL) spiked with LH, FSH, TSH. 1 reagent lot.
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Sample Matrix Comparison: At least 40 serum/plasma pairs were tested in one run.
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Method Comparison to Predicate: 131 samples covering the measuring range. Tested with 1 run per sample.
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Data Provenance (Country of Origin): The document does not explicitly state the country of origin for the data. Given Roche Diagnostics' global presence, the studies could have been conducted in various locations.
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Retrospective or Prospective: These studies appear to be prospective analytical performance studies, specifically designed and executed to evaluate the device characteristics described. The phrases "Precision was evaluated...", "LoB ... was determined...", "A method comparison ... was conducted..." all indicate planned experiments.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
This section is not applicable as the Elecsys HCG STAT is an in vitro diagnostic (IVD) immunoassay, not an AI or imaging device requiring human expert ground truth for interpretation of images or clinical cases. The "ground truth" for its performance is established through quantitative measurements against known standards, spiked samples, and comparison to a legally marketed predicate device.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This section is not applicable for the same reason as point 3. Adjudication methods like 2+1 or 3+1 are typically used for establishing ground truth in clinical evaluations where there is subjective human interpretation (e.g., radiology reads) and disagreement among readers needs resolution.
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
This section is not applicable. The Elecsys HCG STAT is an automated immunoassay for quantitative determination of hCG. It does not involve human readers interpreting output that would be improved or supplemented by AI. It is a standalone diagnostic test.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, a standalone performance evaluation was completed. The studies described (precision, detection limits, linearity, interference, method comparison) are all evaluations of the Elecsys HCG STAT immunoassay system (reagent + instrument) performance without human intervention in the measurement process. The results generated by the device are quantitative values of hCG concentration.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this device's performance evaluation typically involves:
- Known concentrations: For studies like LoD, LoQ, Linearity, Interference, where samples are prepared with known, precise concentrations of hCG or interfering substances.
- Standardized materials: Traceability to the 4th International Standard for Chorionic Gonadotropin from NIBSC code 75/589.
- Quantitative measurements by a predicate device: For method comparison studies, the predicate device's results serve as a reference for comparison, establishing "ground truth" for demonstrating substantial equivalence.
- Reference measurement procedures: Although not explicitly stated, general analytical performance studies rely on highly accurate reference methods or certified reference materials where available.
8. The sample size for the training set
This section is not applicable. The Elecsys HCG STAT is an immunoassay, not an AI or machine learning algorithm that requires a "training set" in the computational sense. The device's parameters are likely established during development and manufacturing through calibration and optimization procedures, not through a 'training set' of cases as understood in AI studies.
9. How the ground truth for the training set was established
This section is not applicable for the same reason as point 8.
§ 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.