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510(k) Data Aggregation
(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 < 10 pg/mL. | Detection Rate for "at FMP or later": 86.1% (95% CI: 80.4–89.9) of women at FMP or later had a picoAMH level < 10 pg/mL. False Positive Rate for "at FMP or later" (i.e., women misclassified as "at FMP or later" when they are earlier): When picoAMH < 10 pg/mL and True FMP is >5 years FMP: 8.2% (95% CI: 5.0-12.6) When picoAMH < 10 pg/mL and True FMP is <5 years FMP: 38.7% (95% CI: 32.4-45.3) |
| Distinguishing "> 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: 26.5% (95% CI: 20.9-32.7) When picoAMH ≥ 100 pg/mL and True FMP is at FMP or later: 1.7% (95% CI: 0.4-4.4) | |
| Limited Deterministic Value for "10 - 99.9 pg/mL" Range Acknowledgment that AMH values between 10 and 99.9 pg/mL have limited deterministic value and require caution. | The labeling explicitly states: "However, the picoAMH ELISA test result has limited deterministic value when AMH values fall between 10 and 99.9 pg/mL, and test results falling into this range should be interpreted with caution." Detection Rate for "< 5 years from FMP" (i.e., AMH 10-99.9 pg/mL): 34.8% (95% CI: 28.6–41.3) False Positive Rate for "< 5 years from FMP": When picoAMH 10-99.9 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) Positive and Negative Likelihood Ratios (LRs) to aid interpretation for women in the menopausal transition (< 5 years from FMP) compared to adjacent categories. | < 5 years from FMP vs. at FMP or later (AMH 10-99.9 pg/mL): Positive LR: 2.86 (1.94, 4.22) Negative LR: 0.74 (0.67, 0.83) < 5 years from FMP vs. > 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 (< 1.3 pg/mL detected for 600 pg/mL Mature hAMH, which is 0.217%). Pro+Mature hAMH showed expected high reactivity (104.641%). (Details in Section L.1.e) | |
| Hook Effect No hook effect observed up to high AMH concentrations. | No hook effect observed by AMH concentrations in human serum up to 256,000 pg/mL. (Details in Section L.1.e) |
The acceptance criteria are essentially met by the demonstration of these performance characteristics as detailed in the study. The FDA's conclusion that the information is sufficient to classify the device indicates that the submitted data aligned with their requirements for demonstrating safety and effectiveness.
2. Sample Size Used for the Test Set and the Data Provenance
- Sample Size for Test Set: 690 retrospective serum samples.
- Data Provenance: The samples were from 690 apparently healthy women ages 42.9 to 62.4 participating in the Study of Women's Health Across the Nation (SWAN) study. The country of origin of the data is not explicitly stated, but the SWAN study is a well-known multi-site longitudinal study of women in the United States. The data is retrospective, as samples were randomly chosen and assigned from existing collections.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The ground truth for the test set was "Menopausal status for each woman was determined based on time to final menstrual period (FMP)." This is an objective clinical outcome and does not appear to have involved expert interpretation of the samples themselves. Therefore, no experts were used to establish the ground truth for the test set in the sense of a subjective assessment. The FMP is a defined clinical event.
4. Adjudication Method for the Test Set
Since the ground truth was based on the objective clinical outcome of "time to final menstrual period (FMP)," which is a factual event (whether a woman has reached FMP and how long ago), there was no adjudication method required for the ground truth of the test set.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This study evaluated the performance of an in vitro diagnostic (IVD) ELISA kit for measuring AMH levels to aid in determining menopausal status, not a diagnostic imaging or interpretive aid where human readers would typically be involved in AI-assisted vs. non-assisted comparisons.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself, the picoAMH ELISA kit, is a standalone diagnostic test. It measures AMH concentrations quantitatively. The "algorithm" in this context refers to the assay's ability to produce a numerical AMH value, and its performance (e.g., detection rates, likelihood ratios) in discerning menopausal categories is assessed directly from these values against the clinical ground truth. Human-in-the-loop performance is explicitly addressed in the "Indications for Use" and "Special conditions for use statement(s)," which emphasize that the assay "should only be used in conjunction with other clinical and laboratory findings" and "should always be assessed in conjunction with the patient's medical history, clinical examination, and other findings."
7. The Type of Ground Truth Used
The type of ground truth used was outcomes data, specifically:
- "Time to Final Menstrual Period (FMP)"
- Menopausal status categorized into three objective groups: "> 5 years from FMP", "< 5 years from FMP", and "at FMP or later."
8. The Sample Size for the Training Set
The document does not explicitly state a separate training set for the clinical performance evaluation. The 690 samples from the SWAN study were "randomly chosen and assigned to the clinical validation cohort." This suggests these samples were used for validation, not necessarily for training of an algorithm in the traditional sense, as this is an ELISA kit. If any internal models or cut-offs were optimized, this usually occurs during internal development (which is not detailed) rather than presented as a distinct "training set" in this regulatory submission for a laboratory test.
9. How the Ground Truth for the Training Set Was Established
As a separate training set is not explicitly mentioned and this is an ELISA kit, this question is not directly applicable. For the clinical validation set, the ground truth was established by the objective clinical outcome of "time to final menstrual period (FMP)," as described in point 7.
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