(55 days)
Immunoassay for the in vitro quantitative determination of human chorionic gonadotropin in human serum and plasma.
The Elecsys® test principle is based on competition principle. Total duration of assay: 18 minutes (37° C). • 1st incubation (9 minutes): Sample (15 µL), a biotinylated HCG specific antibody (75 µL), and a specific anti-HCG antibody labeled with a ruthenium complex (75 µL). •2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (35 µL), the still-free binding sites of the labeled antibody become occupied, with formation of an antibody-hapten complex. The entire complex is bound to the solid phase via interaction of biotin and streptavidin. •The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame). •Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
The provided document is a 510(k) Summary for the Elecsys® HCG Assay. It compares the performance of the proposed device to a predicate device, the Enzymun® HCG Assay (K896901). The document describes various performance characteristics but does not explicitly state specific acceptance criteria that the device must meet, nor does it detail a study designed to test against such criteria with a clear "pass/fail" outcome based on predefined thresholds. Instead, it presents the performance characteristics of both devices side-by-side.
However, based on the information provided, we can infer some "acceptance criteria" from the comparative data, particularly where the proposed device's performance is presented against the predicate or general good laboratory practice.
Here's an analysis based on the provided text, addressing your specific points:
1. Table of Acceptance Criteria and Reported Device Performance
As explicit acceptance criteria are not stated, the table below presents the performance characteristics of the Elecsys® HCG Assay and, where applicable, compares it to the predicate device, implying that performance within a similar range as the predicate would be considered acceptable for substantial equivalence.
| Feature | Inferred "Acceptance Criteria" (often implied by predicate performance or general standards) | Reported Elecsys® HCG Performance |
|---|---|---|
| Precision | Similar or better %CV than predicate | |
| Within-Run %CV | (Control 1: 4.6%, Control 2: 2.9%, Low: 4.6%, Mid: 2.9%, High: 3.1% for predicate) | Control 1: 4.5%, Control 2: 3.3%, 24.80 mIU/mL, 35.39 mIU/mL, 854.30 mIU/mL |
| Total %CV | (Control 1: 5.7%, Control 2: 4.6%, Low: 5.7%, Mid: 4.6%, High: 4.1% for predicate) | Control 1: 5.8%, Control 2: 3.9%, 24.80 mIU/mL, 35.39 mIU/mL, 854.30 mIU/mL |
| Lower Detection Limit | Similar or lower than predicate (1.5 mIU/mL) | 0.5 mIU/mL |
| Linearity | Similar or wider range with acceptable deviation (predicate: 1.5 - 600 mIU/mL with ±10% deviation) | 0.5 - 1,000 mIU/mL (with a deviation from a linear line of ±10%) |
| Method Comparison (vs. Enzymun-Test® HCG) | Strong correlation (r value close to 1), reasonable slope and intercept | Least Squares: y=1.35x - 9.21, r=0.989, SEE=17.50 |
| Passing/Bablok: y=1.29x - 4.05, r=0.989, SEE=17.50 | ||
| Interfering Substances | No interference at physiological or common interfering concentrations | No interference at: Bilirubin 25 mg/dL, Hemoglobin 1 g/dL, Lipemia 1500 mg/dL, Biotin 30 ng/mL |
| Specificity | Low cross-reactivity with related hormones (e.g., LH, FSH, TSH) | LH: 0.07%, FSH: 0.09%, TSH: 0.000% (at specified levels) |
2. Sample Size Used for the Test Set and Data Provenance
The document provides the following sample sizes for performance studies:
- Precision: N=60 for each control level for Elecsys® HCG (assumed to be a composite of within-run and total precision across runs/days).
- Method Comparison: N=64 for the comparison between Elecsys® HCG and Enzymun-Test® HCG using Least Squares and Passing/Bablok regression.
The data provenance is not explicitly stated beyond being "specific data on the performance of the test." The country of origin and whether the data is retrospective or prospective are not mentioned.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided. For an in vitro diagnostic (IVD) like an HCG assay, the "ground truth" for performance studies typically involves reference methods or established standards for measuring HCG concentrations, not expert interpretation of images or clinical cases. The ground truth for HCG assays is often based on:
- Reference materials with known HCG concentrations.
- Comparisons to a highly reliable reference method or a legally marketed predicate device (as done here).
4. Adjudication Method for the Test Set
This is not applicable for an in vitro diagnostic assay measuring a biomarker. Adjudication methods (like 2+1, 3+1) are typically used for studies involving human interpretation (e.g., radiology studies) where disagreement among reviewers needs a resolution process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This is not applicable as the device is an automated in vitro diagnostic assay, not an imaging device requiring human interpretation in a diagnostic workflow. Therefore, "human readers" and "AI assistance" are not relevant concepts in this context, and no such study would be performed.
6. Standalone (Algorithm Only) Performance
Yes, the studies reported are standalone performance studies for the Elecsys® HCG Assay. The results for precision, detection limit, linearity, method comparison, interfering substances, and specificity represent the inherent performance of the assay system (reagent and instrument) without human-in-the-loop performance considerations beyond standard laboratory procedures.
7. Type of Ground Truth Used
The "ground truth" for these performance studies is established through:
- Known concentrations: For precision, linearity, and interfering substance studies, samples with known or precisely prepared concentrations of HCG are used.
- World Health Organization Standard (WHO) 75/537 (1st IRP): Mentioned as the assay standardization method, indicating that the assay results are traceable to international reference standards for HCG.
- Predicate Device (Enzymun-Test® HCG): For method comparison, the results from the Elecsys® HCG assay are compared against the results from the legally marketed predicate device, with the predicate serving as a comparative reference.
8. Sample Size for the Training Set
The document describes the performance characteristics of the device but does not specify a "training set" sample size. This is typical for a traditional IVD assay where performance is characterized through analytical studies (precision, linearity, etc.) rather than machine learning model training. While "calibration" is mentioned, the data used for establishing the calibration curve is distinct from what would be considered a "training set" in an AI/ML context.
9. How the Ground Truth for the Training Set Was Established
Since there is no "training set" in the machine learning sense, this question is not applicable. The "ground truth" for analytical performance, as described in point 7, is established through reference materials and comparison to a predicate device. The calibration curve for the instrument is "instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code," which is established by the manufacturer using their own extensive data and reference standards.
§ 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.