(346 days)
Not Found
No
The summary describes a standard immunoassay technology and data analysis based on a pre-defined master curve and 2-point calibration. There is no mention of AI, ML, or any algorithms that learn from data.
No
This device is an in vitro diagnostic (IVD) assay used to quantitatively determine anti-Müllerian hormone (AMH) levels, aiding in the assessment of ovarian reserve. It provides diagnostic information and explicitly states it is "not intended to be used for monitoring women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program" nor is it directly involved in treatment or therapy.
Yes
The document explicitly states that the "ADVIA Centaur Anti-Müllerian Hormone (AMH) assay is for in vitro diagnostic use." It also describes its use as an aid in assessing ovarian reserve, which is a diagnostic purpose.
No
The device is an in vitro diagnostic assay that uses chemical reagents and is performed on a specific hardware system (ADVIA Centaur® XP system). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is "for in vitro diagnostic use".
- Sample Type: It measures AMH in "human serum and plasma", which are biological samples taken from the body.
- Purpose: The measurement of AMH is used as an "aid in the assessment of the ovarian reserve in women presenting to fertility clinics", which is a diagnostic purpose.
- Device Description: The description details a "sandwich immunoassay using direct acridinium ester-based chemiluminometric technology", which is a common method for in vitro diagnostic tests.
- Materials: The materials listed are reagents and calibrators used to perform the test on the biological sample outside of the body.
- Performance Studies: The document includes detailed performance studies (Detection Capability, Precision, Linearity, Assay Comparison, etc.) which are typical for IVD devices to demonstrate their analytical and clinical performance.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K170524; Access AMH) indicates that this device is being compared to a previously cleared IVD device, a standard process for regulatory submission of IVDs.
All of these points strongly indicate that the ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay is for in vitro diagnostic use in the quantitative determination of anti-Müllerian hormone (AMH) in human serum and plasma (lithium heparin) using the ADVIA Centaur® XP system.
The measurement of AMH is used as an aid in the assessment of the ovarian reserve in women presenting to fertility clinics. This assay is intended to distinguish between women with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve).
This assay is intended to be used in conjunction with other clinical and laboratory findings, such as AFC, before starting fertility therapy. This assay is not intended to be used for monitoring women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
Product codes (comma separated list FDA assigned to the subject device)
PQO
Device Description
The ADVIA Centaur AMH assay is a sandwich immunoassay using direct acridinium ester-based chemiluminometric technology. Two monoclonal anti-AMH antibodies are employed in the assay. The first antibody in the Lite Reagent is a mouse monoclonal anti-AMH antibody labeled with acridinium ester. The second antibody is a biotinylated mouse monoclonal anti-AMH antibody coupled to streptavidin-coated magnetic particles in the Solid Phase.
A direct relationship exists between the amount of AMH present in the patient sample and the amount of relative light units detected by the system. Dose concentration results (ng/mL) are calculated based on a 2-point calibration from a pre-defined master curve.
Material Description:
ADVIA Centaur AMH ReadyPack® primary reagent pack
Solid Phase
22.0 mL/reagent pack
Streptavidin-coated paramagnetic microparticles (~0.15 mg/mL) with biotinylated mouse monoclonal anti-human AMH antibody (~2 µg/mL) in buffer; sodium azide (
§ 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.
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June 2, 2023
Siemens Healthcare Diagnostics Inc. Mey Vasquez Regulatory Affairs Professional 511 Benedict Avenue Tarrytown, NY 10591
Re: K221801
Trade/Device Name: ADVIA Centaur® Anti-Müllerian Hormone (AMH) Regulation Number: 21 CFR 862.1092 Regulation Name: Anti-Müllerian Hormone Test System Regulatory Class: Class II Product Code: PQO Dated: March 4, 2023 Received: March 7, 2023
Dear Mey Vasquez:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
1
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Paula V. Caposino -S
Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K221801
Device Name
ADVIA Centaur® Anti-Müllerian Hormone (AMH)
Indications for Use (Describe)
The ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay is for in vitro diagnostic use in the quantitative determination of anti-Müllerian hormone (AMH) in human serum and plasma (lithium heparin) using the ADVIA Centaur® XP system.
The measurement of AMH is used as an aid in the assessment of the ovarian reserve in women presenting to fertility clinics. This assay is intended to distinguish between women with AFC (antral follicle count) values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve).
This assay is intended to be used in conjunction with other clinical and laboratory findings, such as AFC, before starting fertility therapy. This assay is not intended to be used for monitoring women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
Type of Use (Select one or both, as applicable)
| ☒ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) Summary
510(k) Summary of Safety and Effectiveness
Introduction: According to the requirements of SMDA 1990 and 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number:
1. Date Prepared
June 1, 2023
2. Applicant Information
Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue, Tarrytown, NY 10591 USA
| Contact: | Mey Vasquez
Regulatory Affairs Professional |
|----------|------------------------------------------------|
| Phone : | (862) 213-8409 |
| E-mail : | mey.vasquez@siemens-healthineers.com |
3. Regulatory Information
Assay
| Full Product Name | ADVIA Centaur Anti-Müllerian Hormone (AMH) |
|---|---|
| Abbreviated Product Name | ADVIA Centaur AMH |
| Trade Name | ADVIA Centaur® Anti-Müllerian Hormone (AMH) |
| Common Name | Anti-Müllerian Hormone Test System |
| Classification Name | Anti-Müllerian Hormone Test System |
| Definition | An Anti-Müllerian hormone test system is an in vitro diagnostic |
| device intended to measure anti-Müllerian hormone in human | |
| serum and plasma. The test is intended to be used as an aid of | |
| assessing ovarian reserve in women. | |
| FDA Classification | Class II |
Siemens Healthcare Diagnostics, Inc. Unrestricted
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510(k) Summary
| Review Panel | Toxicology |
|---|---|
| Product Code | PQO |
| Regulation Number | 21 CFR 862.1092 |
PREDICATE DEVICE 4.
Name of Device: Access AMH
510(k): K170524
5. ASSAY PRINCIPLE
The ADVIA Centaur AMH assay is a sandwich immunoassay using direct acridinium ester-based chemiluminometric technology. Two monoclonal anti-AMH antibodies are employed in the assay. The first antibody in the Lite Reagent is a mouse monoclonal anti-AMH antibody labeled with acridinium ester. The second antibody is a biotinylated mouse monoclonal anti-AMH antibody coupled to streptavidin-coated magnetic particles in the Solid Phase.
A direct relationship exists between the amount of AMH present in the patient sample and the amount of relative light units detected by the system. Dose concentration results (ng/mL) are calculated based on a 2-point calibration from a pre-defined master curve.
DEVICE DESCRIPTION 6.
| Material Description |
|---|
| ADVIA Centaur AMH ReadyPack® primary reagent pack |
| Solid Phase |
| 22.0 mL/reagent pack |
| Streptavidin-coated paramagnetic microparticles (~0.15 mg/mL) with biotinylated |
| mouse monoclonal |
| anti-human AMH antibody (~2 µg/mL) in buffer; sodium azide (ADVIA Centaur AMH ReadyPack® ancillary reagent pack |
| Ancillary Reagent |
| 10.0 mL/reagent pack |
| Mouse monoclonal anti-human AMH antibody labeled with acridinium ester in buffer |
| (~0.6 µg/mL); sodium azide ( 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve). |
This assay is intended to be used in coniunction with other clinical and laboratory findings. such as AFC, before starting fertility therapy. This assay is not intended to be used for monitoring women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
Special Conditions for Use Statement 8.
For Prescription Use
COMPARISION OF TECHNOLOGICAL CHARACTERISTICS WITH THE 9. PREDICATE DEVICE
| Item | Candidate Device
ADVIA Centaur® Anti-Müllerian
Hormone (AMH) | Predicate
Beckman Coulter Access
AMH (K170524) |
|-------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ADVIA Centaur®
Anti-Müllerian Hormone (AMH)
assay is for in vitro diagnostic use
in the quantitative determination of
anti-Müllerian hormone (AMH) in
human serum and plasma (lithium) | The Access AMH assay is a
paramagnetic particle
chemiluminescent immunoassay
for the quantitative
determination of anti-Müllerian
hormone (AMH) levels in human
serum and lithium heparin |
| Item | Candidate Device | Predicate |
| | ADVIA Centaur® Anti-Müllerian
Hormone (AMH) | Beckman Coulter Access
AMH (K170524) |
| | heparin) using the ADVIA
Centaur® XP system.
The measurement of AMH is used
as an aid in the assessment of the
ovarian reserve in women
presenting to fertility clinics. This
assay is intended to distinguish
between women with AFC (antral
follicle count) values > 15 (high
ovarian reserve) and women with
AFC values ≤ 15 (normal or
diminished ovarian reserve).
This assay is intended to be used
in conjunction with other clinical
and laboratory findings,
such as AFC, before starting
fertility therapy. This assay is not
intended to be used for
monitoring women undergoing
controlled ovarian stimulation in an
Assisted Reproduction
Technology program. | plasma using the Access
Immunoassay Systems as an
aid in 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).
The Access AMH is intended to
be used in conjunction with
other clinical and laboratory
findings such as antral follicle
count, before starting fertility
therapy. The Access AMH is not
intended to be used for
monitoring of women
undergoing controlled ovarian
stimulation in an Assisted
Reproduction Technology
program. |
| Indications for
Use | Same as Intended Use (Candidate) | Same (for Predicate) |
| | Similarities | |
| LoB | 0.010 ng/mL | ≤ 0.01 ng/mL |
| LoD | 0.020 ng/mL | ≤ 0.02 ng/mL |
| Item | Candidate Device | Predicate |
| | ADVIA Centaur® Anti-Müllerian
Hormone (AMH) | Beckman Coulter Access
AMH (K170524) |
| LoQ | 0.043 ng/mL | ≤ 0.08 ng/mL |
| Measurement | Quantitative | Same |
| Technology | Chemiluminescence | Same |
| Operating
Principle | 1-Step Sandwich immunoassay | Same |
| Sample type | Plasma (lithium heparin) and
Serum | Same |
| Standardization | Traceable to an internal standard
manufactured using highly purified
material | Same |
| Clinical Cut-Off | 1.77 ng/mL to distinguish women
with an antral follicle count (AFC)
15 or ≤ 15. | Same |
| Intended Use
Population(s) | Women presenting to fertility clinics | Same |
| | Differences | |
| Calibration | 2 levels | 6 levels |
| Assay Range | 0.043–24.0 ng/mL | 0.08 – 24 ng/mL |
| Hook Effect | No hook effect up to 1151 ng/mL | No hook effect up to 1000 ng/mL |
| Sample Volume | 100 µL | 20 µL |
| Detection
Antibody | Mouse monoclonal anti-human
AMH antibody labeled with
acridinium ester in buffer | Mouse monoclonal anti-AMH
antibody conjugated to alkaline
phosphatase in MES buffer |
| Item | Candidate Device | Predicate |
| | ADVIA Centaur® Anti-Müllerian
Hormone (AMH) | Beckman Coulter Access
AMH (K170524) |
| Capture
Antibody | Monoclonal mouse anti-human
AMH antibody (~2 µg/mL)
labeled with biotin bound to
streptavidin magnetic particles
(~0.15 mg/mL) in buffer | Mouse monoclonal anti-AMH
antibody bound to para
magnetic particles in buffer |
| Precision (Total
CV) | ≤ 10% CV for concentration ≥0.100
ng/mL | ≤ 10% CV for concentration ≥
0.16 ng/mL |
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510(k) Summary
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510(k) Summary
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510(k) Summary
PERFORMANCE CHARACTERISTICS DATA 10.
10.1. Detection Capability
The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI protocol EP17-A2.
The ADVIA Centaur AMH assay has an LoB of 0.010 ng/mL (0.071 pmol/L), an LoD of 0.020 ng/mL (0.143 pmol/L), and an LoQ of 0.043 ng/mL (0.307 pmol/L).
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510(k) Summary
10.2. Precision
Precision was determined in accordance with CLSI Document EP05-A3.22 Testing was performed using 2 instruments and 3 reagent lots. Samples were assayed in replicates of 2 with 2 runs per day using a 20-day protocol.
The following results are representative of the performance of the assay:
| | | | Repeatability | | Within-Laboratory Precision | | Reproducibility
(Total Imprecision) | |
|-----------|-----|-----------------|----------------|------------|-----------------------------|-----------|----------------------------------------|-----------|
| Sample | Na | Mean
(ng/mL) | SDb
(ng/mL) | CVc
(%) | SD
(ng/mL) | CV
(%) | SD
(ng/mL) | CV
(%) |
| Serum A | 480 | 0.112 | 0.0032 | 2.9 | 0.0036 | 3.2 | 0.0049 | 4.4 |
| Serum B | 480 | 0.193 | 0.0046 | 2.4 | 0.0053 | 2.7 | 0.0066 | 3.4 |
| Serum C | 480 | 0.969 | 0.0205 | 2.1 | 0.0236 | 2.4 | 0.0240 | 2.5 |
| Serum D | 480 | 3.60 | 0.092 | 2.6 | 0.107 | 3.0 | 0.115 | 3.2 |
| Serum E | 480 | 6.71 | 0.156 | 2.3 | 0.198 | 3.0 | 0.224 | 3.3 |
| Serum F | 480 | 6.93 | 0.158 | 2.3 | 0.177 | 2.6 | 0.206 | 3.0 |
| Serum G | 480 | 16.2 | 0.34 | 2.1 | 0.40 | 2.5 | 0.52 | 3.2 |
| Serum H | 480 | 16.4 | 0.37 | 2.3 | 0.42 | 2.6 | 0.47 | 2.9 |
| Control 1 | 480 | 0.955 | 0.0252 | 2.6 | 0.0284 | 3.0 | 0.0312 | 3.3 |
| Control 2 | 480 | 4.75 | 0.120 | 2.5 | 0.135 | 2.8 | 0.140 | 2.9 |
| Control 3 | 480 | 14.1 | 0.33 | 2.3 | 0.37 | 2.6 | 0.41 | 2.9 |
a Number of measurements.
b Standard deviation.
Coefficient of variation.
Siemens Healthcare Diagnostics, Inc. Unrestricted
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510(k) Summary
10.3. Reproducibility
Reproducibility was determined in accordance with CLSI Document EP05-A3. Samples were assayed in triplicate in 2 runs per day for 5 days using 3 sites and 1 reagent lot. The following results are representative of the performance of the assay:
| Repeatability | Between-Run | Between-Day | Between-Site | Reproducibility | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| Sample | Na | (ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | (ng/mL) | ||||||
| Serum A | 90 | 0.199 | 0.0041 | 2.1 | 0.0027 | 1.4 | 0.0000 | 0.0 | 0.0025 | 1.3 | 0.0055 | 2.8 | |
| Serum B | 90 | 1.01 | 0.025 | 2.5 | 0.000 | 0.0 | 0.016 | 1.6 | 0.007 | 0.7 | 0.031 | 3.1 | |
| Serum C | 90 | 3.73 | 0.058 | 1.6 | 0.039 | 1.0 | 0.000 | 0.0 | 0.033 | 0.9 | 0.077 | 2.1 | |
| Serum D | 90 | 6.96 | 0.105 | 1.5 | 0.158 | 2.3 | 0.000 | 0.0 | 0.071 | 1.0 | 0.203 | 2.9 | |
| Serum E | 90 | 17.0 | 0.31 | 1.8 | 0.31 | 1.8 | 0.00 | 0.0 | 0.06 | 0.4 | 0.44 | 2.6 | |
| Control 1 | 90 | 1.01 | 0.022 | 2.2 | 0.017 | 1.7 | 0.005 | 0.5 | 0.008 | 0.8 | 0.029 | 2.9 | |
| Control 2 | 90 | 4.87 | 0.080 | 1.6 | 0.046 | 0.9 | 0.090 | 1.8 | 0.034 | 0.7 | 0.134 | 2.8 | |
| Control 3 | 90 | 14.4 | 0.30 | 2.1 | 0.17 | 1.2 | 0.17 | 1.2 | 0.00 | 0.0 | 0.38 | 2.6 |
a Number of measurements.
10.4. Linearity
Linearity testing was performed in accordance with CLSI Document EP06-A. The ADVIA Centaur AMH assay is linear for the measuring interval of 0.043-24.0 ng/mL (0.307-171 pmol/L).
Assay Comparison 10.5.
Assay comparison was determined with the Passing-Bablok regression model in accordance with CLSI Document EP09c-ed3.
The assay is designed to have a correlation coefficient of ≥ 0.950, a slope of 1.00 ± 0.10, and an intercept of ± 0.035 ng/mL
| Specimen Type | Comparative Assay (x) | Regression Equation | Sample Interval | Na | rb |
|---|---|---|---|---|---|
| Serum | commercial AMH assay | $y = 1.04x - 0.032 ng/mL$ | |||
| ( $y = 1.04x - 0.228 pmol/L$ ) | 0.080–22.0 ng/mL | ||||
| (0.571–157 pmol/L) | 120 | 0.994 |
a Number of samples tested.
b Correlation coefficient.
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510(k) Summary
10.6. Specimen Equivalence
Specimen equivalency was determined with the weighted Deming regression model in accordance with CLSI Document EP09c-ed3.
The assay is designed to have a correlation coefficient of ≥ 0.950, a slope of 0.90-1.10, and an intercept of ± 0.035 ng/mL.
| Tube (y) vs. Serum (x) | Regression Equation | Sample Interval | Na | rb |
|---|---|---|---|---|
| Gel-barrier tube (serum) | $y = 1.00x + 0.003$ ng/mL | |||
| ( $y = 1.00x + 0.021$ pmol/L) | 0.110–19.7 ng/mL | |||
| (0.785-141 pmol/L) | 88 | 0.997 | ||
| Plasma, lithium heparin | $y = 1.08x - 0.004$ ng/mL | |||
| ( $y = 1.08x - 0.029$ pmol/L) | 0.110–19.7 ng/mL | |||
| (0.785-141 pmol/L) | 88 | 0.997 |
Number of samples tested.
b Correlation coefficient.
10.7. Interferences
Hemolysis, Icterus, Lipemia (HIL)
Interference testing was performed in accordance with CLSI Document EP07-ed3. The following substances do not interfere with the assay when present in serum at the concentrations indicated.
Bias due to these substances does not exceed 10% at an AMH concentration of 0.719-0.944 ng/mL (5.13-6.74 pmol/L) and 6.13-6.68 ng/mL (43.8-47.7 pmol/L).
| Substance | Substance Test Concentration |
|---|---|
| Hemoglobin | 1000 mg/dL (10.0 g/L) |
| Bilirubin, conjugated | 66.0 mg/dL (783 µmol/L) |
| Bilirubin, unconjugated | 39.0 mg/dL (667 µmol/L) a |
| Lipemia (Intralipid) | 2000 mg/dL (20.0 g/L) |
a At concentrations ≥ 40 mg/dL, there is statistically significant (>10% bias) interference for unconjugated bilirubin. At 40 mg/dL, the following bias was observed: 10.6% bias at 6.79 ng/mL AMH and 11.4% bias at 0.936 ng/mL AMH.
Other Substances
Interference testing was performed in accordance with CLSI Document EP07-ed3 and EP37-ed1. The following substances do not interfere with the assay when present in serum at the concentrations indicated.
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510(k) Summary
Bias due to these substances does not exceed 10% at an AMH concentration of 0.782–1.38 ng/mL (5.58-9.85 pmol/L) and 5.86-7.49 ng/mL (41.8-53.5 pmol/L).
| Substance | Substance Test Concentration | Substance | Substance Test Concentration |
|---|---|---|---|
| Acetaminophen | 20 mg/dL (1324 µmol/L) | Human IgG | 2500 mg/dL (25.0 g/L) |
| Acetylcysteine | 15.0 mg/dL (920 µmol/L) | Human IgM | 500 mg/dL (5.0 g/L) |
| Acetylsalicylic | |||
| Acid (Aspirin) | 65.0 mg/dL | ||
| (3608 µmol/L) | Ibuprofen | 50.0 mg/dL (2425 µmol/L) | |
| Ampicillin sodium | 100 mg/dL (2693 µmol/L) | Levodopa | 2.00 mg/dL (101 µmol/L) |
| L-Ascorbic acid | 3.00 mg/dL (170 µmol/L) | Levothyroxine | 0.020 mg/dL |
| (0.258 µmol/L) | |||
| Biotin | 0.350 mg/dL | ||
| (14.3 µmol/L) | Metformin | ||
| hydrochloride | 200 mg/dL | ||
| (12,076 µmol/L) | |||
| Cefoxitin sodium salt | 250 mg/dL (5563 µmol/L) | Methyldopa | 2.00 mg/dL (83.9 µmol/L) |
| Cholesterol | 500 mg/dL (13.0 mmol/L) | Metronidazole | 20.0 mg/dL (1168 µmol/L) |
| Cyclosporine | 0.500 mg/dL | ||
| (4.16 µmol/L) | Phenylbutazone | 40.0 mg/dL (1296 µmol/L) | |
| Doxycycline hyclate | 5.00 mg/dL (48.7 µmol/L) | Rheumatoid Factor | 1000 IU/mL |
| Folic acid | 0.040 mg/dL | ||
| (0.906 µmol/L) | Rifampicin | 6.00 mg/dL (73.2 µmol/L) | |
| Gonapeptyl | |||
| (Triptorelin acetate) | 0.010 mg/dL | ||
| (0.073 µmol/L) | Theophylline | 10.0 mg/dL (555 µmol/L) | |
| Heparin | 500 U/dL | Total Protein | 12.0 g/dL (120 g/L) |
| Human IgA | 1800 mg/dL (18.0 g/L) | Uric acid | 25.0 mg/dL (1487 µmol/L) |
10.8. Cross-Reactivity
Cross-reactivity was determined in accordance with CLSI Document EP07-ed3. Crossreactants were tested at anti-Müllerian hormone concentrations of 0 ng/mL (0 pmol/L) and 0.924–1.05 ng/mL (6.60–7.50 pmol/L).
| Cross-reactant | Cross-reactant Concentration | Cross-reactivity (%) |
|---|---|---|
| Activin A | 100 ng/mL (7.69 nmol/L) | ≤0.1 |
| ≤0.1 |
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510(k) Summary
| Cross-reactant | Cross-reactant Concentration | Cross-reactivity (%) |
|---|---|---|
| Activin B | 50.0 ng/mL (3.91 nmol/L) | ≤ 0.1 |
| ≤ 0.1 | ||
| Activin AB | 50.0 ng/mL (1.94 nmol/L) | ≤ 0.1 |
| ≤ 0.1 | ||
| Follicle stimulating hormone | 500 mlU/mL | Not Detectable a |
| 0.2 | ||
| Inhibin A | 100 ng/mL (3.57 nmol/L) | ≤ 0.1 |
| ≤ 0.1 | ||
| Inhibin B | 100 ng/mL (3.08 nmol/L) | ≤ 0.1 |
| ≤ 0.1 | ||
| Luteinizing hormone | 500 mlU/mL | Not Detectable a |
| 2.9 | ||
| TGF b-1 | 65.0 ng/mL (5.08 nmol/L) | ≤ 0.1 |
| ≤ 0.1 |
a FSH and LH were expressed in biological activity units (mIU/mL). The observed analyte dose change was reported as percent dose bias to control sample. Bias does not exceed 10%, and is therefore considered insignificant.
10.9. Stability
The on-board stability of the ADVIA Centaur AMH reagents was determined to be 70 days with a calibration interval of 28 days.
The ADVIA Centaur AMH calibrators when reconstituted were determined to be stable at 2-8°C and ≤ -20°C for 90 days.
10.10. High Dose Hook
High AMH concentrations can cause a paradoxical decrease in the RLUs (high-dose hook effect). In this assay, no hook effect was observed up to 1151 ng/mL (8218 pmo//L).
10.11. Expected Values
Samples were collected prospectively from apparently healthy subjects. The 90th reference interval was determined by calculating the 5th and 95th percentiles of the distribution of values.
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510(k) Summary
The 95th reference interval was determined by calculating the 2.5th and 97.5th percentiles of the distribution of values.
| Group | Na | Median
ng/mL
(pmol/L) | 90% Reference Interval
ng/mL (pmol/L) | 95% Reference Interval ng/mL
(pmol/L) |
|------------------------------------|-----|-----------------------------|------------------------------------------|------------------------------------------|
| Females
(18–25
years) | 209 | 4.70
(33.6) | 1.28–11.8 (9.14–84.3) | 1.02–15.6 (7.28–111) |
| Females
(26–30
years) | 122 | 3.80
(27.1) | 0.843–8.81 (6.02–62.9) | 0.520–10.0 (3.71–71.4) |
| Females
(31–35
years) | 123 | 2.70
(19.3) | 0.772–8.07 (5.51–57.6) | 0.676–10.2 (4.83–72.8) |
| Females
(36–40
years) | 126 | 1.59
(11.4) | 0.156–6.13 (1.11–43.8) | 0.079–8.66 (0.564–61.8) |
| Females
(41–45
years) | 152 | 0.493
(3.52) | 35 years of age) using results of the clinical data (n=533) was performed. The clinical study had 270 subjects evaluated who were 35 years of age. The likelihood of a subject with a result > 1.77 ng/mL having high ovarian reserve was higher in subjects 35 years of age.
| | Females 15) | 67.4% | 38.4% |
| PPV | 73.6% (67.47, 78.88) | 59.7% (51.71, 67.27) |
| NPV | 65.1% (50.17, 77.58) | 89.5% (82.50, 93.88) |
*PPV and NPV are dependent on prevalence
11. CONCLUSION
Comparative testing of the ADVIA Centaur® Anti-Müllerian Hormone (AMH) assay is substantially equivalent in principle and performance to the Predicate Device - Access AMH assay cleared under 510(k) K170524.