(43 days)
The quantitative determination of follicle stimulating hormone (FSH) concentration in human serum and plasma by a microplate enzymeimmunoassay.Measurements of follicle-stimulating hormone are used in the diagnosis of pituitary gland and gonadotropin disorders.
Monobind Inc., registration number 2020726, plans to introduce Into commercial distribution an enzymeimmunoassay (ELISA) kit for the determination of folliclestimulating hormone (FSH) in human serum and plasma.
The Monobind ELISA method is based on two-site immunoassay (sandwich) technology utilizing the streptavidin-blotin reaction to effect separation. Upon mixing monoclonal blotinylated anti-FSH antibody, the enzyme-labeled anti-FSH antibody and a serum containing the native antigen (FSH), reaction results between the native antigen (FSH) and the antibodies, without competition or steric hindrance, to form a soluble sandwich complex. Simultaneously, the complex is deposited to the well through the high affinity reaction of streptavidin and biotinylated antibody. After incubation is complete, decantation or aspiration separates the bound fraction. The enzyme activity on the well Is directly proportional to the native antigen (FSH) concentration. By utilizing several different serum references of known antigen values, a dose response curve can be generated from which the antigen concentration of an unknown can be ascertained.
The provided document describes the Monobind Inc. Follicle-stimulating hormone (FSH) ELISA kit and its submission for 510(k) clearance. The focus of the acceptance criteria and study is on demonstrating substantial equivalence to a predicate device.
Here's an analysis based on the document:
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance and Outcome |
|---|---|---|
| Substantial Equivalence (Clinical Comparison) | Correlation Coefficient: The new device's results should have a strong correlation with the predicate device's results. This implies a high R-value (typically close to 1). |
Linear Regression: The relationship between the new device and the predicate device should be linear, allowing for predictable conversion or direct comparison, expressed as y = mx + b.
Mean Values: The mean values of the new device should be comparable to the predicate device, indicating a similar central tendency in measurements. | Correlation Coefficient: 0.994, indicating very good method agreement.
Linear Regression Equation: y = 0.93(x) - 1.5, showing a strong linear relationship.
Mean Values: Predicate device (ICMA) mean = 21.0 mIU/ml; New device (ELISA) mean = 18.0 mIU/ml. |
| Analytical Recovery | Average Recovery Rate: When exogenous FSH is added to human serum specimens, the device should accurately recover the added amount, reflecting minimal interference or loss. | Average recovery of 99.9% when exogenous added FSH was introduced into human serum specimens. |
| Linearity (Dilution Studies) | Average Linearity: When specimens with varying FSH concentrations are diluted and compared to the dose response curve, the device should maintain accurate and proportional readings, demonstrating linearity across its measurement range. | Average linearity of 93.8% when specimens were diluted and compared to the dose response curve. |
Study Proving Device Meets Acceptance Criteria:
The study proving the device meets the acceptance criteria is a clinical comparison study (sometimes referred to as a method comparison study) specifically designed to demonstrate substantial equivalence to the predicate device, the Ciba Corning ACS 180 chemiluminescence (ICMA) test.
2. Sample Size and Data Provenance:
- Sample Size for Test Set: 128 specimens.
- Data Provenance: The document does not explicitly state the country of origin. However, the manufacturer is Monobind Inc., located in Costa Mesa, CA (USA), and the submission is to the FDA. It is highly probable the data is from the USA. The study used specimens "from low to elevated populations," indicating a range of clinical samples.
- Retrospective or Prospective: Not explicitly stated, but clinical comparison studies for 510(k) submissions are typically prospective or involve retrospectively collected samples that are then prospectively tested with both devices. The phrase "clinical comparison... using 128 specimens" suggests these were real-world samples tested with both methods.
3. Number of Experts and Qualifications:
Not applicable for this type of device and study. The ground truth itself is established by the predicate device's measurement, not by expert consensus on visual assessment or interpretation. For an in vitro diagnostic (IVD) device like an ELISA kit, the "ground truth" for the comparison study is the result from the established, legally marketed predicate device.
4. Adjudication Method:
Not applicable. This is a quantitative measurement device comparison, not an interpretation task requiring adjudication. The "ground truth" is the numerical result from the predicate device.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study:
Not applicable. This is an in vitro diagnostic (IVD) device that provides a quantitative measurement of a biomarker in a sample, not an imaging or diagnostic interpretation device where human readers are involved. Therefore, there is no "human reader" component to improve in this context.
6. Standalone Performance:
Yes, a standalone performance study was done in the sense that the Monobind ELISA kit generated its own quantitative results independent of human interpretation. The study then compared these standalone results to those of the predicate device. The performance characteristics reported (mean values, recovery, linearity) are standalone performance metrics of the Monobind ELISA.
7. Type of Ground Truth Used:
The ground truth for the comparison was the measurement obtained from the legally marketed predicate device, the Ciba Corning ACS 180 chemiluminescence (ICMA) test. This is an accepted method for demonstrating substantial equivalence for IVDs.
8. Sample Size for the Training Set:
The document does not explicitly mention a "training set" in the context of an algorithm or machine learning. For an ELISA kit, "training" might refer to assay development and optimization rather than a separate dataset for an algorithm. The reported 128 specimens were used for the clinical comparison/validation study. There is no indication of a separate training set for a machine learning model.
9. How the Ground Truth for the Training Set was Established:
As there is no explicit mention of a "training set" for an algorithm, this question is not directly applicable. If one considers the process of developing and optimizing the ELISA kit itself (which could be loosely termed "training" for a traditional assay), the "ground truth" would be established by various biochemical and analytical methods to ensure the assay accurately detected and quantified FSH in reference materials and spiked samples. This would precede the formal clinical comparison study.
§ 862.1300 Follicle-stimulating hormone test system.
(a)
Identification. A follicle-stimulating hormone test system is a device intended to measure follicle-stimulating hormone (FSH) in plasma, serum, and urine. FSH measurements are used in the diagnosis and treatment of pituitary gland and gonadal disorders.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.