(376 days)
Not applicable
Not Found
No
The summary describes a standard in vitro diagnostic assay and analyzer, with no mention of AI or ML in the device description, intended use, or performance studies. The performance metrics are based on a fixed cutoff value, not a learned algorithm.
No
This device is an in vitro diagnostic (IVD) system used to measure AMH levels for assessing ovarian reserve, which informs fertility therapy decisions, but it does not directly treat or prevent a disease or condition.
Yes
The device is intended for the quantitative determination of anti-Müllerian hormone (AMH) to assess ovarian reserve and distinguish between different levels of ovarian reserve in women presenting to fertility clinics. This information is used in conjunction with other clinical and laboratory findings before fertility therapy, which constitutes a diagnostic purpose.
No
The device is an in vitro diagnostic system that includes reagents, calibrators, and controls, intended for use on a specific analyzer (cobas e 411). This involves physical components and chemical processes, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "Elecsys AMH system... is intended for use in the in vitro quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma."
This statement clearly indicates that the device is designed to perform tests on samples taken from the human body (in vitro) to measure a specific substance (quantitative determination of AMH). This aligns with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Elecsys AMH system, consisting of the Elecsys AMH CalSet, PreciControl AMH, and AMH CalCheck 5, is intended for use in the in vitro quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. The determination of AMH is used for the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values >15 (high ovarian reserve) and women with AFC values ≤15 (normal or diminished ovarian reserve). This system is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy. The Elecsys AMH system is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
The Elecsys AMH system is intended for use on cobas e 411 analyzer.
AMH CalSet is used for calibrating the quantitative Elecsys AMH assay.
PreciControl AMH is used for quality control of the Elecsys AMH assay.
AMH CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established for the Elecsys AMH assay.
Product codes (comma separated list FDA assigned to the subject device)
POO, JIT, JJX
Device Description
The Elecsys AMH reagent working solutions are packed in Rack Pack (kit placed on analyzer), which include:
- Streptavidin-coated microparticles (transparent cap). 1 bottle. 6.5 mL: Streptavidin-. coated microparticles 0.72 mg/mL; preservative.
- Reagent 1: Anti-AMH-Ab~biotin (gray cap), 1 bottle, 8 mL: Biotinylated monoclonal anti-AMH antibody (mouse) 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5: preservative.
- Reagent 2: Anti-AMH-Ab~Ru(bpy)32+ (black cap), 1 bottle, 8 mL: Monoclonal . anti-AMH antibody (mouse) labeled with ruthenium complex 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5; preservative.
The AMH CalSet is a lyophilized equine serum matrix with endogenous AMH (Cal 1) and a lyophilized equine serum matrix with added bovine AMH (Cal 2). The CalSet includes:
- AMH Cal 1: approximately 0.04 ng/mL endogenous AMH in an equine serum matrix, . preservative.
- AMH Cal 2: approximately 8 ng/mL bovine AMH in an equine serum matrix, preservative.
PreciControl AMH is a lyophilized equine serum matrix with added bovine AMH (male fetal bovine serum) in two concentration ranges. The controls are used for monitoring the accuracy and precision of the Elecsys AMH assay. PreciControl AMH includes:
- PC AMH 1: approximately 1 ng/mL bovine AMH in an equine serum matrix, preservative.
- PC AMH 2: approximately 5 ng/mL bovine AMH in an equine serum matrix, ● preservative.
AMH CalCheck 5 is a (b) (4)
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The clinical study for assessing ovarian reserve included women presenting at fertility clinics for evaluation. The reference range study was conducted on apparently healthy females of reproductive age between 20 and 44 years.
Intended User / Care Setting
Fertility clinics and laboratory settings.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical study:
Sample size: N = 856 women
Data source: Multicenter, prospective, non-interventional study; Patient BMI ranged from 14.76 to 39.99. Clinical serum samples were collected at 13 geographically diverse sites in the United States.
Annotation protocol: AMH values were correlated to the antral follicle count (AFC) of the women. AFC was determined by transvaginal ultrasonography (TVUS), which measures antral follicles (2-10 mm) of the ovary. Both AFC and AMH were determined on days 2-4 of the same menstrual cycle. Samples were tested at 3 laboratory sites in the United States on cobas e 411 analyzers. Two groups were defined based on AFC: AFC ≤ 15 and AFC > 15.
Reference range study:
Sample size: 718 apparently healthy females
Data source: Native serum samples
Annotation protocol: Testing was conducted at two sites to establish age-dependent reference ranges.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Studies:
- Study type: Multicenter, prospective, non-interventional study investigating the use of AMH for assessment of ovarian reserve.
- Sample size: N = 856 women presenting at fertility clinics.
- Standalone performance: The AMH cutoff, intended to predict an antral follicle count (AFC) >15, is 1.77 ng/mL.
- Key results:
- Correlation of AMH (using the 1.77 ng/mL cutoff) and AFC (>15 vs. ≤15):
- AMH ≤ 1.77 ng/mL: 280 (84.3%) with AFC ≤ 15; 52 (15.7%) with AFC > 15
- AMH > 1.77 ng/mL: 130 (24.8%) with AFC ≤ 15; 394 (75.2%) with AFC > 15
- Key Metrics:
- PPV: 75.2% (95% CI: 71.3-78.8%)
- NPV: 84.3% (95% CI: 80.0-88.1%)
- Sensitivity: 88.3% (95% CI: 85.0-91.2%)
- Specificity: 68.3% (95% CI: 63.6-72.8%)
- Correlation of AMH (using the 1.77 ng/mL cutoff) and AFC (>15 vs. ≤15):
Precision/Reproducibility:
- Study type: Internal precision study and external reproducibility study.
- Sample size: Internal: 5 human serum samples and 2 controls (N = 84 for each). External: 5 serum pools and 2 controls (N=90 for each).
- Key results:
- Internal Precision: %CVs for human serum samples ranged from 1.3% to 2.3% (Repeatability) and 1.6% to 2.3% (Intermediate Precision).
- External Reproducibility: %CVs for serum samples ranged from 3.45% to 5.24% (Total) and 1.41% to 1.89% (Repeatability).
Linearity/Assay Reportable Range:
- Study type: Linearity evaluation according to CLSI EP6-A.
- Sample size: Three high level samples diluted to 15 concentration levels.
- Key results: Correlation coefficients (r) were 0.999 for all three sample sets, supporting the claimed measuring range of 0.03 ng/mL - 23 ng/mL.
Detection Limit:
- Study type: Determination of LoB, LoD, and LoQ in accordance with CLSI EP17-A2.
- Key results:
- Limit of Blank (LoB): 0.007 ng/mL
- Limit of Detection (LoD): 0.01 ng/mL
- Limit of Quantitation (LoQ): 0.03 ng/mL
Analytical Specificity (Endogenous and Exogenous Interference, Cross-reactivity, Hook Effect):
- Study type: Interference and cross-reactivity studies.
- Key results: No significant interference for various endogenous and exogenous substances at specified concentrations.
§ 862.1092 Anti-mullerian hormone test system.
(a)
Identification. An anti-mullerian hormone test system is an in vitro diagnostic device intended to measure anti-mullerian hormone in human serum and plasma. An anti-mullerian hormone test system is intended to be used for assessing ovarian reserve in women.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) An adequate traceability plan to minimize the risk of drift in anti-mullerian hormone test system results over time.
(ii) Detailed documentation of a prospective 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 adequate clinical performance relative to a well-accepted comparator.
(B) Clinical sample results must demonstrate consistency of device output throughout the device measuring range that is appropriate for the intended use population.
(C) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the proposed indications for use(s), and results of all statistical analyses.
(iii) Reference intervals generated by testing an adequate number of samples from apparently healthy normal individuals in the intended use population.
(2) The labeling required under § 809.10(b) of this chapter must include a warning statement that the device is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy, and that the device should be used in conjunction with the antral follicle count.
0
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR Elecsys AMH system
DECISION SUMMARY
A. DEN Number:
B. Purpose for Submission:
De Novo request for evaluation of automatic class III designation of the Elecsys AMH system
C. Measurand:
AMH (Anti-Müllerian [Mullerian] Hormone)
D. Type of Test:
Electrochemiluminescence immunoassay
E. Applicant:
Roche Diagnostics
F. Proprietary and Established Names:
Elecsys AMH system including the following: Elecsys AMH assay AMH CalSet PreciControl AMH AMH CalCheck 5
G. Regulatory Information:
-
- Regulation Section:
21 CFR 862.1092. Anti-mullerian hormone test system
- Regulation Section:
2. Classification:
Class II (Special Controls)
1
-
- Product Code(s):
POO JIT JJX
- Product Code(s):
-
- Panel:
91 - Toxicology
- Panel:
H. Indications for use:
-
- Indication(s) for use:
Elecsys AMH system, consisting of the Elecsys AMH CalSet, PreciControl AMH, and AMH CalCheck 5, is intended for use in the in vitro quantitative determination of anti-Müllerian hormone (AMH) in human serum and lithium heparin plasma. The determination of AMH is used for the assessment of ovarian reserve in women presenting to fertility clinics. This system is intended to distinguish between women presenting with AFC (antral follicle count) values >15 (high ovarian reserve) and women with AFC values ≤15 (normal or diminished ovarian reserve). This system is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy. The Elecsys AMH system is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
- Indication(s) for use:
The Elecsys AMH system is intended for use on cobas e 411 analyzer.
AMH CalSet is used for calibrating the quantitative Elecsys AMH assay.
PreciControl AMH is used for quality control of the Elecsys AMH assay.
AMH CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established for the Elecsys AMH assay.
-
- Special conditions for use statement(s):
For Prescription Use Only
- Special conditions for use statement(s):
Samples for AMH levels should be drawn on days 2-4 of the menstrual cycle
The Elecsys AMH assay is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy (including pre-treatment such GnRH agonist down-regulation therapy) and should be used in conjunction with AFC. The Elecsys AMH assay is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
2
3. Special instrument requirements:
For use on the cobas e 411 analyzer
I. Device Description:
The Elecsys AMH reagent working solutions are packed in Rack Pack (kit placed on analyzer), which include:
- Streptavidin-coated microparticles (transparent cap). 1 bottle. 6.5 mL: Streptavidin-. coated microparticles 0.72 mg/mL; preservative.
- . Reagent 1: Anti-AMH-Ab~biotin (gray cap), 1 bottle, 8 mL: Biotinylated monoclonal anti-AMH antibody (mouse) 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5: preservative.
- Reagent 2: Anti-AMH-Ab~Ru(bpy)32+ (black cap), 1 bottle, 8 mL: Monoclonal . anti-AMH antibody (mouse) labeled with ruthenium complex 1.0 mg/L, phosphate buffer 50 mmol/L, pH 7.5; preservative.
The AMH CalSet is a lyophilized equine serum matrix with endogenous AMH (Cal 1) and a lyophilized equine serum matrix with added bovine AMH (Cal 2). The CalSet includes:
- AMH Cal 1: approximately 0.04 ng/mL endogenous AMH in an equine serum matrix, . preservative.
- . AMH Cal 2: approximately 8 ng/mL bovine AMH in an equine serum matrix, preservative.
PreciControl AMH is a lyophilized equine serum matrix with added bovine AMH (male fetal bovine serum) in two concentration ranges. The controls are used for monitoring the accuracy and precision of the Elecsys AMH assay. PreciControl AMH includes:
- . PC AMH 1: approximately 1 ng/mL bovine AMH in an equine serum matrix, preservative.
- PC AMH 2: approximately 5 ng/mL bovine AMH in an equine serum matrix, ● preservative.
| AMH CalCheck 5 is a | (b) (4) |
|---|---|
| (b) (4) | |
| (b) (4) |
3
J. Standard/Guidance Document Referenced:
CLSI EP05-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition
CLSI EP6-A: Evaluation of Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline
CSLI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- Second Edition
K. Test Principle:
The Elecsys AMH assay makes use of a sandwich test principle using monoclonal antibodies that are specifically directed against AMH. Endogenous AMH is bound by both a biotinylated monoclonal AMH-specific antibody and a monoclonal AMH-specific antibody labeled with a ruthenium complex to form a sandwich complex. Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.
L. Performance Characteristics:
-
- Analytical performance:
- a. Precision/Reproducibility:
Precision:
An internal precision study was performed in accordance with CLSI EP05-A2, in which 5 human serum samples and 2 controls were tested in 2 replicates per run x 2 runs per day for 21 days (N = 84) on the cobas e 411 analyzer. The following results were obtained:
| Sample
Material | Mean
(ng/mL) | Repeatability (Within Run) | | Intermediate Precision | |
|--------------------|-----------------|----------------------------|------|------------------------|------|
| | | SD | % CV | SD | % CV |
| Control 1 | 1.14 | 0.017 | 1.4 | 0.018 | 1.6 |
| Control 2 | 5.61 | 0.088 | 1.6 | 0.101 | 1.8 |
| Human Serum 1 | 0.055 | 0.001 | 1.6 | 0.001 | 2.3 |
| Human Serum 2 | 1.05 | 0.014 | 1.3 | 0.019 | 1.8 |
| Human Serum 3 | 3.56 | 0.055 | 1.5 | 0.058 | 1.6 |
| Human Serum 4 | 11.7 | 0.113 | 1.0 | 0.144 | 1.2 |
| Human Serum 5 | 19.0 | 0.265 | 1.4 | 0.281 | 1.5 |
Reproducibility:
At 3 external laboratory sites, 5 serum pools spiked with bovine AMH and 2 levels of PreciControl AMH were tested in triplicates per day for 5 days on the cobas e 411 analyzer. The results are summarized in the table below:
4
| Sample | Precision
Type | N | Mean | SD (95% CI) | %CV (95% CI) |
|-----------|-------------------|----|-------|----------------------|--------------------|
| Control 1 | Total | 90 | 0.93 | 0.049 (0.032, 0.099) | 5.24 (3.46, 10.69) |
| | Repeatability | | | 0.013 (0.011, 0.016) | 1.42 (1.21, 1.73) |
| Control 2 | Total | 90 | 4.87 | 0.228 (0.155, 0.434) | 4.70 (3.18, 8.91) |
| | Repeatability | | | 0.092 (0.078, 0.112) | 1.89 (1.60, 2.30) |
| Serum 1 | Total | 90 | 0.26 | 0.010 (0.007, 0.020) | 3.99 (2.68, 7.77) |
| | Repeatability | | | 0.004 (0.004, 0.005) | 1.58 (1.34, 1.92) |
| Serum 2 | Total | 90 | 1.24 | 0.050 (0.034, 0.092) | 4.05 (2.79, 7.42) |
| | Repeatability | | | 0.022 (0.018, 0.026) | 1.74 (1.48, 2.12) |
| Serum 3 | Total | 90 | 3.55 | 0.123 (0.083, 0.237) | 3.45 (2.33, 6.66) |
| | Repeatability | | | 0.050 (0.042, 0.061) | 1.41 (1.19, 1.71) |
| Serum 4 | Total | 90 | 9.63 | 0.445 (0.290, 0.944) | 4.62 (3.01, 9.80) |
| | Repeatability | | | 0.163 (0.138, 0.198) | 1.69 (1.44, 2.06) |
| Serum 5 | Total | 90 | 20.12 | 0.880 (0.592, 1.707) | 4.38 (2.94, 8.48) |
| | Repeatability | | | 0.340 (0.289, 0.414) | 1.69 (1.43, 2.06) |
b. Linearity/assay reportable range:
Linearity:
Linearity of the Elecsys AMH Assay were evaluated according to CLSI EP6-A. Three high level samples were diluted with postmenopausal female serum for a total of 15 concentration levels. Samples were assayed in triplicate on the cobas e 411 analyzer. The observed values were graphed against the calculated values and a linear regression was performed. Results are summarized in the table below:
| Sample | Sample range (ng/mL) | Slope | Intercept | Correlation (r) |
|---|---|---|---|---|
| Set 1 | 0.004 – 27.5 | 1.0091 | 0.0105 | 0.999 |
| Set 2 | 0.004 - 27.4 | 1.0054 | 0.0205 | 0.999 |
| Set 3 | 0.004 - 25.8 | 1.0063 | 0.0013 | 0.999 |
The linear regression results support the Applicant's claimed measuring range (0.03
5
ng/mL - 23 ng/mL).
Dilution:
A dilution study was performed by diluting six human samples with Diluent Universal in 1:2 ratio both manually and by the analyzer. The data support the following instruction for use:
Samples with AMH concentrations above the measuring range can be diluted automatically with Diluent Universal 2. Manual dilution can be performed with Diluent Universal 2. The recommended dilution is 1:2 (either automatically by the cobas e analyzer or manually). The concentration of the diluted sample must be > 10 ng/mL. After manual dilution, multiply the result by the dilution factor. After dilution by the analyzer, the cobas e software automatically takes the dilution into account when calculating the sample concentration.
- Traceability, Stability, Expected values (controls, calibrators, or methods): C.
Traceability:
The AMH CalSet are traceable to manufacturer's internal reference standards (Master Calibrators), which consist of a panel of well characterized serum reference materials covering the entire measuring range. The Applicant submitted a detailed traceability assurance plan which was reviewed and found to be acceptable. The target values for AMH CalSet are shown below:
| Level | Target Value
(ng/mL) | Target Range
(ng/mL) |
|--------------|-------------------------|-------------------------|
| Calibrator 1 | 5 mg/day)
7
until at least 8 hours following the last biotin administration.
Exogenous interference
Exogenous interference was evaluated by spiking pharmaceutical compounds (at 2 concentrations with the higher concentration corresponding to at least 3 times the maximum recommended daily dose) into two human serum sample pools with low and high AMH levels. Each sample was tested in triplicate. The Applicant states in their submission that interference is considered to be significant if analyte recovery is outside of ± 10% of the initial value.
The highest concentrations of exogenous substances tested that show non-signifficant interference are summarized in the table below:
| Substance | Highest concentration tested with
no significant interference (mg/L) |
|----------------------|-------------------------------------------------------------------------|
| Acetylcysteine | 150 |
| Ampicillin-Na | 1000 |
| Ascorbic acid | 300 |
| Cyclosporine | 5 |
| Cefoxitin | 2500 |
| Heparin | 5000 U |
| Levodopa | 20 |
| Methyldopa +1.5 | 20 |
| Metronidazole | 200 |
| Phenylbutazone | 400 |
| Doxycycline | 50 |
| Acetylsalicylic Acid | 1000 |
| Rifampicin | 60 |
| Acetaminophen | 200 |
| Ibuprofen | 500 |
| Theophylline | 100 |
| Gonapeptyl | 0.1 |
| Metformin | 2000 |
| Folic Acid | 0.4 |
| Levothyroxine | 0.2 |
The labeling for this device states the following limitation:
The following drugs may interfere with this test: Cetrotide, Ovitrelle, Endometrin and Follistatin; do not use this test to analyze samples from patients who have received one or more of these products within one to two weeks of testing.
Cross-reactivity:
The cross reactivity of the Elecsys AMH assay was evaluated using samples composed of Diluent Universal spiked with potential cross-reacting compounds. All
8
| Cross-reactant | Concentration tested |
|---|---|
| Inhibin A | 100 ng/mL |
| Activin A | 100 ng/mL |
| LH | 500 mIU/mL |
| FSH | 500 mIU/mL |
samples were tested in duplicate and 15, is 1.77 ng/mL.
-
- Comparison studies:
- a. Method comparison with predicate device:
Not applicable
- b. Matrix comparaison:
The clinical study used to demonstrate clinical performance of the assay was performed in serum samples (see section L(3)(a) below). To demonstrate that Li-Heparin plasma samples perform equivalently to serum samples, 75 matched serum/Li-Heparin plasma samples with AMH concentrations covering the entire measuring range were tested on the cobas e 411 analyzer, and the results were assessed by Passing/Bablok regression analysis.
| Slope | Intercept | Correlation coefficient (r) |
|---|---|---|
| 1.017 | -0.00186 | 0.999 |
-
- Clinical studies:
- a. Clinical sensitivity and specificity:
Clinical Studies:
The use of AMH for the assessment of ovarian reserve was investigated in a multicenter, prospective, non-interventional study with N = 856 women presenting at fertility clinics for evaluation. Patient BMI included in the study ranged from 14.76 to 39.99, as shown below:
9
| BMI | N |
|---|---|
| 30.00-39.99 | 158 |
AMH values were correlated to the antral follicle count (AFC) of the women. AFC was determined by transvaginal ultrasonography (TVUS), which measures antral follicles (2-10 mm) of the ovary. Both AFC and AMH were determined on days 2-4 of the same menstrual cycle. Clinical serum samples were collected at 13 geographically diverse sites in the United States, and then tested at 3 laboratory sites in the United States on cobas e 411 analyzers.
Based on the AFC, two groups are defined: AFC ≤ 15 and AFC > 15. Correlation of AMH (using the 1.77 ng/mL cutoff) and AFC is presented in the table below (relationship is shown in both absolute numbers and percentages per AMH group):
| AFC ≤ 15 | AFC > 15 | N | |
|---|---|---|---|
| AMH ≤ 1.77 ng/mL | 280 | ||
| (84.3 %) | 52 | ||
| (15.7 %) | 332 | ||
| AMH > 1.77 ng/mL | 130 | ||
| (24.8 %) | 394 | ||
| (75.2 %) | 524 | ||
| N | 410 | 446 | 856 |
The following figure illustrates the Validation Arm AMH results, presented by AFC group/class (AFC 15).
10
Image /page/10/Figure/0 description: The image shows a boxplot comparing AMH levels in ng/mL for two AFC classes, 0-15 and >15. The sample size for the 0-15 class is N=410, while the sample size for the >15 class is N=446. The AMH levels appear to be higher in the >15 AFC class compared to the 0-15 class, as indicated by the position of the boxes and the median values represented by the '+' symbols.
Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity for predicting AFC > 15 (with 95% confidence intervals in parentheses) observed in the study using the 1.77 ng/mL cutoff are summarized in the following table:
| Result | 95% CI | |
|---|---|---|
| PPV | 75.2% | (71.3-78.8%) |
| NPV | 84.3% | (80.0-88.1%) |
| Sensitivity | 88.3% | (85.0-91.2%) |
| Specificity | 68.3% | (63.6-72.8%) |
-
b. Other clinical supportive data (when a. is not applicable):
Not applicable. -
- Clinical cut-off:
The AMH cutoff, intended to predict an antral follicle count (AFC) >15, is 1.77 ng/mL.
- Clinical cut-off:
-
- Expected values/Reference range:
A reference range study was conducted to establish age-dependent reference ranges for AMH in 718 apparently healthy females of reproductive age between 20 and 44 years. Native serum samples were collected and testing was conducted at two sites. The reference range values for different age groups are summarized below:
- Expected values/Reference range:
11
| Healthy
Women
(years) | N | 2.5%-q
ng/mL
(95% CI) | 5%-q
ng/mL
(95% CI) | Median
ng/mL
(95% CI) | 95%-q
ng/mL
(95% CI) | 97.5%-q
ng/mL
(95% CI) |
|-----------------------------|-----|-----------------------------|---------------------------|-----------------------------|----------------------------|------------------------------|
| 20-24 | 150 | 1.22
(0.478-1.67) | 1.52
(0.758-1.81) | 4.00
(3.60-4.44) | 9.95
(7.87-13.6) | 11.7
(9.11-15.7) |
| 25-29 | 150 | 0.890
(0.493-1.21) | 1.20
(0.797-1.75) | 3.31
(3.00-3.89) | 9.05
(7.59-10.3) | 9.85
(8.91-11.3) |
| 30-34 | 138 | 0.576
(0.256-0.958) | 0.711
(0.256-1.12) | 2.81
(2.35-3.47) | 7.59
(6.84-9.52) | 8.13
(7.27-9.72) |
| 35-39 | 138 | 0.147
(0.053-0.474) | 0.405
(0.053-0.496) | 2.00
(1.73-2.36) | 6.96
(5.31-9.37) | 7.49
(6.49-10.9) |
| 40-44 | 142 | 0.030
(0.030-0.063) | 0.059
(0.030-0.119) | 0.882
(0.726-1.13) | 4.44
(2.94-5.56) | 5.47
(3.92-6.76) |
M. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type.
N. Identified Risks and Identified Mitigations:
| Identified Risks to Health | Identified Mitigations |
|---|---|
| Inaccurate test results that provide false positive results | |
| may lead to a modification, delay or cancellation before a | |
| controlled ovarian stimulation procedure is initiated. | General controls and special |
| controls (1) and (2) | |
| Inaccurate test results that provide false negative results | |
| may lead to the development of ovarian hyperstimulation | |
| syndrome in patients incorrectly thought to have normal | |
| and/or diminished ovarian reserve. | General controls and special |
| controls (1) and (2) |
12
O. Benefit/Risk Analysis:
| Summary | |
|---|---|
| Summary of | |
| the Benefit(s) | The primary benefit of the Elecsys AMH system is its use in the prediction (in |
| conjunction with other clinical and laboratory findings) of high ovarian | |
| reserve. The assessment of ovarian reserve prior to performing controlled | |
| ovarian stimulation (COS) can assist in the reduction of risk of patients | |
| developing ovarian hyperstimulation syndrome (OHSS) by identifying those | |
| patients with a higher OHSS risk (i.e., those with high ovarian reserve levels, | |
| which correspond to an antral follicle count (AFC) of >15). | |
| The AMH cut-off corresponding to an AFC > 15 was validated with a | |
| sensitivity and specificity of 88.3% and 68.3%, respectively. | |
| Summary of | |
| the Risk(s) | The primary risks to patients through the use of the device are related to the |
| consequences of clinical decisions based on false positive and the more | |
| clinically significant false negative results. | |
| False positive results may lead to a modification, delay or cancellation before | |
| a controlled ovarian stimulation procedure is initiated. Modifications to a | |
| stimulation regimen may lead to less oocytes for fertilization. False positive | |
| results may result in the need for a repeat procedure and cancelled or delayed | |
| stimulation. | |
| False negative results may lead to the development of ovarian | |
| hyperstimulation syndrome, a potentially life-threatening condition, in | |
| patients incorrectly thought to have normal and/or diminished ovarian reserve. | |
| However, this risk can be mitigated through appropriate labeling indicating | |
| that AMH assay is intended to be used for assessing the ovarian reserve in | |
| conjunction with other clinical and laboratory findings before starting any | |
| fertility therapy, and should be used in conjunction with Antral Follicle Count. | |
| Additional risks to patients and laboratory workers include those that are | |
| associated with routine phlebotomy performed as standard practice in a | |
| clinical setting. | |
| Summary of | |
| Other Factors | There are no additional factors to consider. |
| Summary | |
| Conclusions | |
| Do the | |
| probable | |
| benefits | |
| outweigh the | |
| probable risks? | Given the performance characteristics, applicable general controls, including |
| design controls, and proposed special controls, including labeling | |
| mitigations, the probable benefits outweigh the probable risks for this device. |
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Patient Perspectives:
This submission did not include specific information on patient perspectives for this device.
P. Conclusion:
| Product Code: | PQO, JIT, JJX |
|---|---|
| Device Type: | Anti-mullerian hormone test system |
| Class: | II (special controls) |
| Regulation: | 21 CFR 862.1092 |
- a) Identification. An anti-mullerian hormone test system is an in vitro diagnostic device intended to measure anti-mullerian hormone in human serum and plasma. An antimullerian hormone test system is intended to be used as an aid for assessing ovarian reserve in women.
- b) Classification. Class II (special controls). An anti-mullerian hormone test system must comply with the following special controls:
-
- Premarket notification submissions must include the following information:
- An adequate traceability plan to minimize the risk of drift in anti-1. mullerian hormone test system results over time.
- ii. Detailed documentation of a prospective clinical study to demonstrate clinical performance or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
- Results must demonstrate adequate clinical performance relative to a. a well-accepted comparator.
- b. Clinical sample results must demonstrate consistency of device output throughout the device measuring range that is appropriate for the intended use population.
- c. Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the proposed indications for use(s), and results of all statistical analyses.
- iii. Reference intervals generated by testing an adequate number of samples from apparently healthy normal individuals in the intended use population.
-
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-
- Your 809.10(b) compliant labeling must include a warning statement that the device is intended to be used for assessing the ovarian reserve in conjunction with other clinical and laboratory findings before starting any fertility therapy, and that the device should be used in conjunction with the Antral Follicle Count.