(275 days)
The picoAMH ELISA is an enzyme-linked immunosorbent assay (ELISA) for the in vitro quantitative measurement of anti-Müllerian hormone (AMH), also known as Müllerian Inhibiting Substance (MIS), concentrations in human serum. It is intended to be used as an aid in the determination of menopausal status in women between 42 and 62 years of age. This assay should only be used in conjunction with other clinical and laboratory findings and results from this test alone should not be used to make diagnostic or treatment decisions. It is intended for in vitro diagnostic use and for prescription use only.
The picoAMH ELISA device is supplied as a reagent kit containing the following components in buffer with preservatives:
- AMH/MIS (Müllerian Inhibiting Substance) Coated Microtitration strips: one strip-● holder, containing 12 strips and 96 microtitration wells with mouse monoclonal AMH antibody immobilized to the inside wall of each well.
- AMH/MIS Assay Buffer: one 12 mL bottle containing protein-based buffer with preservative.
- picoAMH Biotin Conjugate Ready-To-Use: one 12 mL bottle containing biotinylated ● mouse anti-AMH antibody in protein-based buffer with preservative.
- picoAMH Streptavidin-Enzyme Conjugate Ready-To-Use: one 12 mL bottle containing streptavidin-HRP (horseradish peroxidase) in a protein-based buffer and preservative.
- . TMB Chromogen Solution: one 12 mL bottle containing a solution of tetramethylbenzidine (TMB) in buffer with hydrogen peroxide.
- Stopping Solution: one 12 mL bottle containing 0.2 M sulfuric acid. ●
- Wash Concentrate A: one 60 mL bottle containing buffered saline with a nonionic ● detergent that requires a 25-fold dilution with deionized water prior to use.
Acceptance Criteria and Device Performance for picoAMH ELISA
This document details the acceptance criteria for the picoAMH ELISA and the results of the clinical study conducted to demonstrate the device meets these criteria.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes the clinical performance of the picoAMH ELISA in distinguishing menopausal categories. The acceptance criteria are implicitly derived from these reported performance metrics, particularly the detection rates and likelihood ratios for specific AMH cut-offs.
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Clinical Performance | Distinguishing "at FMP or later" | |
| High detection rate for women at FMP or later having picoAMH 5 years FMP: 8.2% (95% CI: 5.0-12.6) | ||
| When picoAMH 5 years from FMP"** | ||
| High detection rate for women > 5 years from FMP having picoAMH > 100 pg/mL. | Detection Rate for "> 5 years from FMP": 82.2% (95% CI: 76.6–86.9) of women > 5 years from FMP had a picoAMH level > 100 pg/mL. | |
| False Positive Rate for "> 5 years from FMP" (i.e., women misclassified as "> 5 years from FMP" when they are closer): | ||
| When picoAMH ≥ 100 pg/mL and True FMP is 5 years FMP: 9.6% (95% CI: 6.1-14.1) | ||
| When picoAMH 10-99.9 pg/mL and True FMP is at FMP or later: 12.2% (95% CI: 8.2, 17.1) | ||
| Likelihood Ratios for Menopausal Transition ( 5 years from FMP (AMH 10-99.9 pg/mL): | ||
| Positive LR: 3.64 (2.35, 5.62) | ||
| Negative LR: 0.72 (0.65, 0.80) | ||
| Analytical Performance | Precision/Reproducibility | |
| Low coefficient of variations (CV%) for repeatability and intermediate precision across different AMH concentrations and reagent lots. | Repeatability %CV ranged from 2.5% to 5.5%. Intermediate Precision %CV ranged from 3.7% to 8.1%. (Details in Section L.1.a) | |
| Linearity/Assay Reportable Range | ||
| Data supports a claimed measuring range. | The data supports the claimed measuring range of 6.0 to 1150 pg/mL. (Details in Section L.1.b) | |
| Dilution | ||
| Data supports dilution instructions for samples above the measuring range. | The data support measurements up to 23,000 pg/mL when diluted up to 20-fold. (Details in Section L.1.b) | |
| Detection Limit | ||
| Established Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ). | LoB = 0.5 pg/mL, LoD = 1.3 pg/mL, LoQ = 3.2 pg/mL. (Details in Section L.1.d) | |
| Analytical Specificity (Interference) | ||
| No significant interference from common endogenous and exogenous substances at specified concentrations. | The table in Section L.1.e lists numerous substances and their highest concentrations tested without significant interference (>10% difference). Biotin specifically showed no interference up to 10,000 ng/mL. | |
| Analytical Specificity (Cross-reactivity) | ||
| Low cross-reactivity with structurally related and other relevant compounds. | None of the potential cross-reactants (e.g., Activin B, Inhibin A, Inhibin B, Follistatin, Myostatin, FSH, TSH, LH, Prolactin, Testosterone, Estrone Sulphate, DHEA, Progesterone, Estradiol) showed > 0.5% cross-reactivity. Mature hAMH also showed low cross-reactivity ( 5 years from FMP", " |
§ 862.1093 Menopause test system.
(a)
Identification. A menopause test system is an in vitro diagnostic device intended to measure hormones or other analytes in human clinical specimens as an aid in the determination of menopausal status in women.(b)
Classification. Class II (special controls). A menopause test system must comply with the following special controls:(1) Design verification and validation must include the following:
(i) An appropriate traceability plan to minimize the risk of drift in the menopause test system results over time.
(ii) Detailed documentation of a clinical study to demonstrate clinical performance or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(A) Results must demonstrate appropriate clinical performance relative to a well-accepted and appropriate comparator.
(B) Data must demonstrate accuracy of device output for each indicated specimen type throughout the device measuring range as appropriate for the intended use population.
(2) The labeling required under § 809.10 of this chapter must include the following:
(i) A statement in the indications for use that the device is intended to be used for the determination of menopausal status only in conjunction with other clinical and laboratory findings prior to any diagnostic or treatment decisions.
(ii) A limiting statement that the device is intended to be used for the determination of menopausal status only in conjunction with other clinical and laboratory findings prior to any diagnostic or treatment decisions.
(iii) A limiting statement appropriately describing the risks of false test results and that test results should not be relied upon in clinical decision making (
e.g., to discontinue contraceptive use and/or to evaluate patients for the presence of endometrial cancer) without other clinical and laboratory findings.