(275 days)
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No
The device description and performance summary describe a standard ELISA assay kit and its performance metrics, with no mention of AI or ML algorithms used in the analysis or interpretation of results.
No
The device is an in vitro diagnostic (IVD) test, specifically an ELISA, intended for quantitative measurement of AMH to aid in determining menopausal status. It is explicitly stated that it should not be used to make treatment decisions, which is a characteristic of a diagnostic device, not a therapeutic one. Therapeutic devices are used for treatment or prevention of disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended to be used as an aid in the determination of menopausal status in women between 42 and 62 years of age" and "It is intended for in vitro diagnostic use". While it states "results from this test alone should not be used to make diagnostic or treatment decisions," it is still an aid in diagnosis, fitting the definition of a diagnostic device.
No
The device description clearly outlines a reagent kit containing various chemical components and physical elements like microtitration strips, which are hardware components necessary for performing the ELISA assay. This is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use Statement: The "Intended Use / Indications for Use" section explicitly states: "It is intended for in vitro diagnostic use and for prescription use only." This is a clear declaration of its intended purpose as an IVD.
- Measurement of Analyte in Human Sample: The device measures the concentration of anti-Müllerian hormone (AMH) in human serum. IVDs are designed to perform tests on samples taken from the human body.
- Aid in Determination of Medical Condition: The intended use is "as an aid in the determination of menopausal status". While not a standalone diagnostic, it provides information used in the diagnostic process.
- Device Description: The description details a reagent kit used for an ELISA, which is a common laboratory technique for measuring substances in biological samples. This aligns with the nature of IVD devices.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
QDH
Device Description
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.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
42 and 62 years of age
Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
A clinical study was performed to evaluate the clinical performance of the device. 690 retrospective serum samples from 690 apparently healthy women ages 42.9 to 62.4 (no history of ovarian surgery, no diagnosis of PCOS, no oral contraceptive intake) participating in the Study of Women's Health Across the Nation (SWAN) study were randomly chosen and assigned to the clinical validation cohort. Each woman contributed one sample and one outcome to the study. The sponsor provided data supporting the stability of the frozen serum specimens used in the clinical validation study for the length and conditions of storage of SWAN study specimens. Menopausal status for each woman was determined based on time to final menstrual period (FMP). The sponsor defined three menopausal status categories: "> 5 years from FMP", "=100 pg/mL, >5 years from FMP: 82.2% (76.6–86.9)
For =100 pg/mL, Classified >5 years from FMP, True =100 pg/mL, Classified >5 years from FMP, True at FMP or later: 1.7% (0.4-4.4)
For 5 years from FMP: 8.2% (5.0-12.6)
Likelihood Ratios for comparison of women 5 years from FMP: Positive Likelihood Ratio: 3.64 (2.35, 5.62), Negative Likelihood Ratio: 0.72 (0.65, 0.80)
The picoAMH ELISA performs reasonably well in distinguishing women at FMP or later and women > 5 years from FMP.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
LoB = 0.5 pg/mL
LoD = 1.3 pg/mL
LoQ = 3.2 pg/mL
Detection Rate (%):
For >=100 pg/mL, >5 years from FMP: 82.2% (76.6–86.9)
For =100 pg/mL, Classified >5 years from FMP, True =100 pg/mL, Classified >5 years from FMP, True at FMP or later: 1.7% (0.4-4.4)
For 5 years from FMP: 8.2% (5.0-12.6)
Positive Likelihood Ratio ( 5 years from FMP): 3.64 (2.35, 5.62)
Negative Likelihood Ratio ( 5 years from FMP): 0.72 (0.65, 0.80)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
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Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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N/A
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EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR picoAMH ELISA
DECISION SUMMARY
A. DEN Number:
B. Purpose for Submission:
New device
C. Measurand:
Anti-Müllerian Hormone (AMH)
D. Type of Test:
Quantitative enzyme-linked immunosorbent assay (ELISA)
E. Applicant:
Ansh Labs
F. Proprietary and Established Names:
picoAMH ELISA
G. Regulatory Information:
| Regulation | Name | Product Code | Panel |
|---|---|---|---|
| 21 CFR 862.1093 | Menopause test system | QDH | Chemistry (75) |
H. Indications for Use:
-
- Indication(s) for use:
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.
- Indication(s) for use:
1
-
- Special conditions for use statement(s):
For prescription use only.
- Special conditions for use statement(s):
picoAMH results should always be assessed in conjunction with the patient's medical history, clinical examination, and other findings when being interpreted for diagnostic purposes.
picoAMH test results 10 pg/mL should be carefully evaluated in the context of a full clinical work up to ensure that uterine bleeding due to endometrial cancer is not dismissed as a potential diagnosis.
This test should not be used to assess a woman's fertility status or for use in monitoring or predicting the ovarian response in women undergoing or planning to undergo fertility treatments.
3. Special instrument requirements:
Microplate reader capable for absorbance measurement at 450 nm, 405 nm, and 630 nm.
I. Device Description:
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.
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J. Standard/Guidance Document Referenced (if applicable):
CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Methods, 3rd Edition
CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approach, 2nd Edition
CLSI EP07-A2: Interference Testing in Clinical Chemistry, 2nd Edition
CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures, 2nd Edition
CLSI EP25-A: Evaluation of Stability of In Vitro Diagnostic Reagents, 1st Edition
CLSI CP28-A3c: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, Third Edition
K. Test Principle:
The picoAMH ELISA is a quantitative three-step sandwich type immunoassay that is designed to measure human AMH. In the first step, calibrators, controls, and unknown samples are added to AMH antibody-coated microtiter wells. After an incubation and washing, biotinylated AMH antibody solution is added. After a second incubation and washing, the wells are incubated with streptavidin horseradish peroxidase conjugate (SHRP) solution. Finally, after a third incubation and washing step, the wells are incubated with substrate solution (TMB) followed by an acidic stopping solution.
The AMH antibody-biotin conjugate binds to the solid phase antibody-antigen complex, which in turn binds to the streptavidin-enzyme conjugate. The antibody-antigen-biotin conjugate-SHRP (streptavidin horseradish peroxidase conjugate solution) complex bound to the well is detected by enzyme-substrate reaction. The degree of enzymatic turnover of the substrate is determined by dual wavelength absorbance measurement at 450 nm as the primary test filter and 630 nm as the reference filter. The absorbance measured is directly proportional to the concentration of AMH in the calibrators, controls, and specimens tested.
L. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision was evaluated using four human serum specimens containing AMH concentrations ranging from about 15 pg/mL to about 930 pg/mL. Samples were tested at one site in replicates of four, in two runs per day, for 20 days with three reagent lots (n = 160 per lot).
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| Sample | Lot | N | Mean
pg/mL | Repeatability
SD (pg/mL) | Repeatability
% CV | Intermediate
Precision
SD (pg/mL) | Intermediate
Precision
%CV |
|---------|-----|-----|---------------|-----------------------------|-----------------------|-----------------------------------------|----------------------------------|
| Serum 1 | 1 | 160 | 14.6 | 0.8 | 5.5% | 1.2 | 8.1% |
| | 2 | 160 | 14.2 | 0.6 | 4.2% | 0.8 | 5.9% |
| | 3 | 160 | 15.5 | 0.7 | 4.5% | 1.0 | 6.7% |
| Serum 2 | 1 | 160 | 80.1 | 2.2 | 2.8% | 3.6 | 4.5% |
| | 2 | 160 | 80.0 | 2.0 | 2.5% | 3.4 | 4.2% |
| | 3 | 160 | 80.8 | 2.8 | 3.5% | 3.4 | 4.2% |
| Serum 3 | 1 | 160 | 620.3 | 17.4 | 2.8% | 22.9 | 3.7% |
| | 2 | 160 | 609.6 | 16.8 | 2.8% | 24.2 | 4.0% |
| | 3 | 160 | 643.2 | 19.2 | 3.0% | 24.0 | 3.7% |
| Serum 5 | 1 | 160 | 942.8 | 28.9 | 3.1% | 51.3 | 5.4% |
| | 2 | 160 | 924.1 | 23.7 | 2.6% | 48.5 | 5.3% |
| | 3 | 160 | 935.2 | 36.8 | 3.9% | 47.4 | 5.1% |
Results for within-lab imprecision are as follows:
b. Linearity/assay reportable range:
Linearity
Linearity was evaluated based on CLSI EP06-A. A high analyte (1200 pg/mL) concentration specimen ("High Pool") was prepared by adding recombinant human AMH to low-analyte pooled human serum. 14 intermediate levels were prepared by mixing low-analyte serum with the High Pool for a total of 16 level (b) (4) Each level was measured in triplicate with three lots and the allowable nonlinearity was calculated for each lot. Representative data for one reagent lot is shown below:
y =(b) (4)
The data supports the sponsor's claimed measuring range of 6.0 to 1150 pg/mL.
Dilution
A dilution study was performed using nine human serum samples spiked with recombinant AMH (ranging from (b) (4) pg/mL). Samples were manually diluted 20-fold with picoAMH Calibrator A/Sample diluent and tested in triplicate using four reagent lots. The data support the sponsor's instructions for use stating that samples containing AMH concentrations above the claimed measuring range (6 to 1150 pg/mL) and up to 23,000 pg/mL can be measured with the picoAMH ELISA assay when diluted up to 20-fold.
- c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The picoAMH ELISA assay is traceable to an internal recombinant AMH standard
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manufactured at Ansh Labs. The applicant submitted a detailed traceability assurance plan which was reviewed and found to be acceptable.
The picoAMH Calibrators consist of a picoAMH Calibrator A/Sample Diluent containing AMH in equine serum with preservative. The target values for the calibrators are shown below:
| Calibrator | AMH Concentration
(pg/mL) |
|------------|------------------------------|
| CAL A | 0 |
| CAL B | 8 |
| CAL C | 31 |
| CAL D | 105 |
| CAL E | 360 |
| CAL F | 1091 |
The picoAMH Controls consist of two vials, labeled Levels I and II, containing low and high AMH concentrations in serum with preservative. Controls are reconstituted with 1 mL of deionized water.
- d. Detection limit:
Detection limits were evaluated based on CLSI EP17-A2.
The Limit of Blank (LoB) was evaluated using 18 independent human serum pools containing no detectable AMH. Samples were tested with four reagent lots for a total of 73 replicates per specimen. The overall LoB (n = 324) was calculated using a nonparametric analysis.
The Limit of Detection (LoD) and Limit of Quantitation (LoQ) were evaluated using 12 low-level serum pools (containing between 2.76 and 9.95 pg/mL AMH) measured over four reagent lots (n = 144 per lot). The LoD was calculated as the Mean LoB + 1.645*SDL (SDL = standard deviation ofpooled low level specimens). The sponsor defined the LoQ as the lowest amount of analyte in a sample that can be quantified reliably with an intra-assay coefficient of variance (CV) of 20% based on precision profiling.
The data supports the following claims:
LoB = 0.5 pg/mL
LoD = 1.3 pg/mL
LoQ = 3.2 pg/mL
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e. Analytical specificity:
Endogenous and exogenous interference
Endogenous and exogenous interference was evaluated according to CLSI EP07-A2 using low (27 pg/mL) and high (300 pg/mL) serum samples spiked with possible interferents. High samples were tested in replicates of six and low samples were tested in replicates of four. Test samples were compared to control samples without interferent. The sponsor considered a percent difference between test samples and control samples of >10% to be significant interference.
The highest concentrations of endogenous and exogenous substances tested that show non-significant interference are summarized in the table below:
| Substance | Highest Concentration Tested
Without Significant Interference |
|-------------------------------------------|------------------------------------------------------------------|
| Acetaminophen | 0.2 mg/mL |
| Acetylcysteine | 0.15 mg/mL |
| Acetylsalicylic acid | 1 mg/mL |
| Ampicillin-Na | 1 mg/mL |
| Ascorbic acid | 0.3 mg/mL |
| Bazedoxifene | 1 µg/mL |
| Bilirubin | 0.66 mg/mL |
| Biotin* | 10,000 ng/mL |
| Bisphosphonate
(Alendronate (Fosamax)) | 0.02 mg/mL |
| Cefoxitin Na | 2.5 mg/mL |
| Cholesterol | 5 mg/mL |
| Citalopram | 0.01 mg/mL |
| Cyclosporine | 5 µg/mL |
| Cyproterone acetate | 0.3 mg/mL |
| Doxycycline Hyclate | 50 µg/mL |
| Escitalopram Oxalate | 0.1 mg/mL |
| Estradiol (beta) | 1 ng/mL |
| Estrone sulfate | 1 ng/mL |
| Estropipate | 0.015 mg/mL |
| Fluoxetine HCl | 3.5 µg/mL |
| Folic Acid | 0.4 µg/mL |
| Gabapentin | 0.09 mg/mL |
| Hemoglobin (Human) | 10 mg/mL |
| Heparin | 30 U/mg |
| Ibuprofen | 0.5 mg/mL |
| Levodopa | 30 µg/mL |
| Levonorgestrel | 3 µg/mL |
| Levothyroxine | 0.2 µg/mL |
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| Substance | Highest Concentration Tested
Without Significant Interference |
|-----------------------------|------------------------------------------------------------------|
| Medroxyprogesterone acetate | 1 µg/mL |
| Metformin | 2 mg/mL |
| Methyldopa | 0.02 mg/mL |
| Metronidazole | 0.2 mg/mL |
| Norethindrone | 0.03 mg/mL |
| Paroxetine HCl | 1 µg/mL |
| Phenylbutazone | 0.1 mg/mL |
| Pregabalin | 0.01 mg/mL |
| Progesterone | 0.4 mg/mL |
| Raloxifene HCl | 0.12 mg/mL |
| Rifampicin | 60 µg/mL |
| Theophylline | 0.1 mg/mL |
| Intralipid 20% | 20 mg/mL |
| Triptorelin acetate | 15 µg/mL |
| Venlafaxine HCl | 15 µg/mL |
- Though this assay uses biotin-streptavidin binding technology, no interference is observed in specimens containing up to 10,000 ng/mL biotin.
Cross-reactivity
The cross reactivity of the picoAMH ELISA assay was evaluated using pooled serum samples containing undetectable concentrations of AMH spiked with potential crossreacting compounds. Pro+Mature recombinant human AMH was included as a positive control. All samples were tested in duplicate with a single reagent lot. The AMH measured as pg/mL after addition was used to calculate a percent cross reactivity based on the mass of potential cross reactant tested as follows:
% cross reactivity = (2.5 pg/mL divided by pg/mL cross-reactant tested) x 100
For cross-reactants yielding detectable AMH concentrations, the formula for calculating percent cross reactivity was:
% cross-reactivity = ((measured value - true value)/concentration of cross-reactant tested)*100)
| Cross-Reactant | Concentration Tested
(pg/mL) | AMH Value
(pg/mL) | % Cross-
reactivity |
|----------------|---------------------------------|----------------------|------------------------|
| Activin B | 50,000 | 0.5% cross-reactivity.
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| Cross-Reactant | Concentration Tested
(pg/mL) | AMH Value
(pg/mL) | % Cross-
reactivity |
|------------------|---------------------------------|----------------------|------------------------|
| alpha-2 | 65.000 | 5 years from FMP", " 5 years", " 5 years from FMP | 5 years from FMP | 5 years from FMP | 82.2
(76.6–86.9) | ≥100 pg/mL | >5 years from FMP | 5 years from FMP | at FMP or later | 1.7
(0.4-4.4) |
| 10-99.9 pg/mL | 5 years from FMP | 8.2
(5.0-12.6) |
| 5 years from FMP | 9.6
(6.1-14.1) | | | |
| 10-99.9 pg/mL | 5 years from FMP. Specifically, 86.1% of women who were at FMP or later also had a picoAMH level 5 years from FMP also had a picoAMH level > 100 pg/mL.
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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."
To aid in the interpretation of picoAMH ELISA test results obtained for women in the menopausal transition (i.e., 5 years from FMP | 3.64
(2.35, 5.62) | 0.72
(0.65, 0.80) |
The results above show that, comparing to any woman with an unknown AMH level who has reached her FMP or is 5 years away from her FMP, a woman with an AMH test result between 10 and 99.9 pg/mL is 3.64 times more likely to be 5 years away from her FMP.
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a. Clinical Sensitivity:
Not applicable. -
b. Clinical specificity:
Not applicable. -
c. Other clinical supportive data (when a. and b are not applicable):
Not applicable. -
- Clinical cut-off:
The sponsor specified two clinical cut-offs for the pico AMH ELISA assay: 100 pg/mL to distinguish women > 5 years from FMP.
- Clinical cut-off:
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5. Expected values/Reference range:
A reference range was determined by analyzing 644 serum samples from 644 apparently healthy women enrolled in the SWAN study. The picoAMH test results for these samples was then stratified into four different age groups and percentiles calculated. The results are as follows:
| Age (years) | N | picoAMH ELISA test result centile | CI for 95th centile | ||||
|---|---|---|---|---|---|---|---|
| 5th | 25th | 50th | 75th | 95th | |||
| 42.9 to 44.9 | 159 |