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 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.

Device Description

The Access AMH assay, Access AMH Calibrators, Access AMH QC, along with the Access 2 Immunoassay System analyzer comprise the Access Immunoassay System for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and plasma.

AI/ML Overview

This document describes the Beckman Coulter Access AMH assay, a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels. It is intended as an aid in assessing ovarian reserve in women presenting to fertility clinics 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). The document outlines various analytical and clinical studies to demonstrate the device's performance.

Here's an analysis of the provided information, structured according to your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for each parameter, but it implies performance goals based on its design and comparisons. I will present the stated design goals/expectations as acceptance criteria and the reported performance.

Acceptance Criteria (Design Goal / Expectation)	Reported Device Performance
Limit of Blank (LoB): ≤ 0.01 ng/mL (0.07 pmol/L)	LoB: 0.0040 ng/mL (0.029 pmol/L)
Limit of Detection (LoD): ≤ 0.02 ng/mL (0.14 pmol/L)	LoD: 0.0098 ng/mL (0.07 pmol/L)
Imprecision: Total imprecision ≤ 10% CV for concentrations ≥ 0.16 ng/mL; Total SD ≤ 0.032 ng/mL at concentrations < 0.16 ng/mL	Precision Summary (Access 2 - three lots combined): - Sample 1 (0.09 ng/mL): Total SD = 0.005, %CV = 5.5 - Sample 2 (2.61 ng/mL): Total SD = 0.075, %CV = 2.9 - Sample 3 (8.56 ng/mL): Total SD = 0.282, %CV = 3.3 - Sample 4 (17.16 ng/mL): Total SD = 0.502, %CV = 2.9
Reproducibility: (Implied to be within acceptable clinical performance for multi-site use)	Reproducibility Summary (Access 2, N=320): - Samples (0.48 to 16.16 ng/mL): Total Imprecision (SD and %CV) are provided, ranging from 2.2% to 3.2% CV. - QCs (1.00 to 15.22 ng/mL): Total Imprecision (SD and %CV) are provided, ranging from 2.3% to 3.2% CV.
High-dose Hook Effect: No high-dose hook effect	No high-dose hook effect observed up to 1,000 ng/mL.
Dilution Recovery: Average recovery of 100 ± 10% for 10-fold dilution across the assay range (0-24 ng/mL)	Demonstrated to dilute recover across the range (0-24 ng/mL) with average recovery of 100 ± 10%.
Limit of Quantitation (LoQ): ≤ 0.08 ng/mL (0.57 pmol/L)	LoQ: 0.013 ng/mL (0.093 pmol/L)
Linearity: Maximum deviation from linearity ≤ 5% for samples > 0.16 ng/mL, and ≤ 0.04 ng/mL for samples ≤ 0.16 ng/mL	Maximum deviation from linearity of 4.8% for samples > 0.16 ng/mL. (Statement implies also met for samples ≤ 0.16 ng/mL)
Analytical Specificity: No significant interference (exceeding 10% shift in dose) from listed substances at indicated concentrations	No significant interference observed for tested substances at indicated concentrations.
Cross-reactivity: No significant cross-reactivity (exceeding 5% cross reactivity) from listed substances at indicated concentrations	No significant cross-reactivity observed for tested substances at indicated concentrations.
Matrix Comparison: Slope equal to 1.00 ± 0.10 for different sample types (Lithium Heparin vs. Serum No Gel, Lithium Heparin vs. Serum Gel, Serum Gel vs. Serum No Gel)	Slopes: 1.03 (Lithium Heparin vs. Serum No Gel), 1.05 (Lithium Heparin vs. Serum Gel), 0.99 (Serum Gel vs. Serum No Gel). All within ± 0.10 of 1.00.
Method Comparison (vs. commercially available immunoassay): Strong correlation	Intercept = 0.04 ng/mL, Slope = 1.03 (1.01 – 1.06), Correlation Coefficient (r) = 0.99
Clinical Study (correlation of AMH to AFC): Correlation between AMH values and AFC results (r)	r = 0.77, p < 0.0001
Clinical Study (distinguishing AFC groups): Ability to distinguish women with AFC values > 15 vs. ≤ 15	For AFC > 15 group, with AMH cutoff 1.77 ng/mL: Sensitivity = 88.9%, Specificity = 59.1%. Study supports distinguishing these groups.

2. Sample sizes used for the test set and the data provenance

Clinical Study Test Set:
- Sample Size: 164 women.
- Data Provenance: Prospective, multi-center, conducted at 13 geographically diverse sites in the US.
- Inclusion Criteria: ≥ 21 and < 46 years of age (mean 34.9, range 23-45), in first cycle of ovarian stimulation for IVF or IVF/ICSI, both ovaries present, regular menstrual cycle, no confirmed PCOS. The mean BMI was 25.1 ± 5.3.
- Measurements: AFC and AMH determined on days 2-4 of the same spontaneous menstrual cycle.
Analytical Performance Test Sets (Various):
- Imprecision: N/A (samples were artificial/controls for statistical analysis of variability).
- Reproducibility: N=320 (calculated from 4 instruments, 4 replicates, 2 runs/day, 10 days for 6 samples and 3 QC samples).
- High-dose Hook Effect: N/A (spiked normal human serum).
- Dilution Recovery: N/A (serum and plasma samples across the range).
- Analytical Specificity / Cross-reactivity: N/A (serum samples spiked with interfering/cross-reacting substances).
- Matrix Comparison: 57 matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples.
- Method Comparison: 121 values (samples) across the range of the assay.
- Expected Reference Intervals: Prospectively procured from apparently healthy, non-pregnant females at five (5) geographically diverse sites. Sample sizes per age group: 120 (18-25), 131 (26-30), 120 (31-35), 123 (36-40), 126 (41-45). Subjects had regular menstrual cycles, both ovaries present, and proven fertility.

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 clinical study was Antral Follicle Count (AFC), determined by transvaginal ultrasonography. The document does not specify the number of experts (e.g., sonographers or radiologists) who performed or interpreted these ultrasounds, nor their specific qualifications. It only states an "AFC result was determined by transvaginal ultrasonography, which measured follicles of 2 to 10 mm in diameter."

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable. The ground truth (AFC) was an objective measurement performed via ultrasonography, not a subjective interpretation requiring adjudication among human readers.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is an in-vitro diagnostic (IVD) immunoassay, not an AI-powered image analysis or diagnostic aid for human readers. It provides a quantitative AMH value.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the device's performance is standalone. It's an automated immunoassay system that provides a quantitative AMH measurement directly. The results of the analytical and clinical studies demonstrate this standalone performance. The clinical study correlates the AMH values from the device with AFC, which is a separate clinical measurement, to demonstrate its utility as an "aid in the assessment." The device itself produces a direct, quantitative output.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The primary ground truth for the clinical utility study was Antral Follicle Count (AFC), determined by transvaginal ultrasonography. This is a direct clinical measurement used to assess ovarian reserve.

8. The sample size for the training set

This is an immunoassay technology, not a machine learning algorithm that requires a "training set" in the conventional sense (e.g., for AI model development). The development and calibration of the assay would typically involve extensive analytical studies and optimization using various reagent lots, calibrators, and QC materials, rather than a distinct "training set" of patient data for model learning. The described studies are primarily validation and verification studies.

9. How the ground truth for the training set was established

Not applicable, as this is an immunoassay rather than a machine learning model requiring a "training set" with ground truth in the AI context. The assay itself measures AMH levels directly, and its analytical performance is established through rigorous laboratory testing and comparative studies against predicate devices and clinical parameters like AFC.

Summary

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November 13, 2017

Beckman Coulter, Inc. Debbie Kidder Senior Staff, Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

Re: K170524

Trade/Device Name: Access AMH Regulation Number: 21 CFR 862.1092 Regulation Name: Anti-Mullerian hormone test system Regulatory Class: Class II Product Code: PQO Dated: October 5, 2017 Received: October 6, 2017

Dear Debbie Kidder:

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. 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 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Silver Spring, MD 20993 www.fda.gov_

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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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Courtney)H. Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K170524

Device Name Access AMH

Indications for Use (Describe)

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 K170524

Date Prepared: November 9, 2017

This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92.

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Primary Contact: Debbie Kidder (612)475-6022 (952) 368-7610 (fax)

Alternate Contact:	Angela Kilian
	(952) 368-1330
	(952) 368-7610 (fax)

Device Name

Proprietary / Trade Name: Access AMH Anti-Müllerian hormone test system Common Name: Classification Name: Anti-Müllerian hormone test system Product Code PQO (21 CFR 862.1092)

Predicate Device

Roche Elecsys® AMH System (DEN150057) Manufactured by Roche Diagnostics GmbH

Beckman Coulter Inc. Access AMH Assay Traditional 510(k) Page 1 of 11

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System Description

Intended Use

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Table 1: Comparison of Technological Characteristics to the AMH Assay Predicate

Parameter	Access AMH Assay	PredicateRoche Elecsys® AMH
Indication for Use	The Access AMH assay is a paramagnetic particlechemiluminescent immunoassay for the quantitative determination of anti-Müllerian hormone (AMH) levels in human serum and lithium heparin 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 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 any 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.	The Elecsys AMH system is intended for use for 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. The Elecsys AMH system is intended for use on Cobas e 411 analyzer This system 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 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.
AnalyteMeasured	anti-Müllerian hormone (AMH)	anti-Müllerian hormone (AMH)
Sample Type	Serum or plasma	Serum or plasma
Technology	Sandwich immunoassay	Sandwich immunoassay
Format	Chemiluminescent	Electrochemiluminescence
Method	Automated	Automated
MeasuringRange	0.08 – 24 ng/mL(0.57– 171 pmol/L)	0.01 – 23 ng/mL(0.071 – 164.2 pmol/L)
ReagentStability	Unopened at 2° to 10°C until stated expiration date.	Unopened at 2° to 8°C up to stated expiration date.

Beckman Coulter Inc. Access AMH Assay Traditional 510(k) Page 3 of 11

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Limit of Blank (LoB): Access AMH was designed to have a Limit of Blank of ≤ 0.01 ng/mL (0.07 pmol/L). In one study, LoB testing determined the LoB for Access AMH to be 0.0040 ng/mL (0.029 pmol/L).

Limit of Detection (LoD): The Access AMH assay was designed to have a Limit of Detection (LOD) of ≤ 0.02 ng/mL (0.14 pmol/L). In one study, LoD testing determined the LoD for Access AMH to be 0.0098 ng/mL (0.07 pmol/L).

Imprecision: The AMH assay exhibits total imprecision of less than or equal to 10% CV for concentrations greater than or equal to 0.16 ng/mL, and total standard deviation (SD) ≤0.032 ng/mL at concentrations < 0.16 ng/mL.

	AMH(ng/mL)n=240	Within-run		Between-run		Intra-study(Within Lab)		Inter-study		TotalImprecision
Sample	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	0.09	0.002	2.8	0.001	1.7	0.003	3.3	0.004	4.4	0.005	5.5
Sample 2	2.61	0.052	2.0	0.041	1.6	0.066	2.5	0.035	1.3	0.075	2.9
Sample 3	8.56	0.161	1.9	0.175	2.0	0.238	2.8	0.152	1.8	0.282	3.3
Sample 4	17.16	0.380	2.2	0.289	1.7	0.478	2.8	0.155	0.9	0.502	2.9

Precision Summary of Access 2 - three lots combined

Reproducibility was evaluated at four sites. Six samples spanning the analytical measuring range and three quality control samples were tested. Samples were evaluated on four Access 2 instruments in four replicates with two runs per day for 10 days.

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	ΑΜΗ(ng/mL)N=320	Within Run(Repeatability)		Within Day		BetweenDay		Between Site		Reproducibility(TotalImprecision)
	Mean	SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV
Sample 1	0.48	0.010	2.1	0.003	0.6	0*	NA	0.010	2.1	0.015	3.1
Sample 2	0.94	0.017	2.1	0.001	0.1	0.005	0.5	0.024	2.5	0.030	3.2
Sample 3	2.58	0.049	1.9	0.010	0.4	0.018	0.7	0.055	2.1	0.076	2.9
Sample 4	5.14	0.100	1.9	0.050	1.0	0*	NA	0.094	1.8	0.146	2.8
Sample 5	10.21	0.182	1.8	0.060	0.6	0.051	0.5	0.158	1.5	0.253	2.5
Sample 6	16.16	0.292	1.8	0.107	0.7	0*	NA	0.181	1.1	0.360	2.2
QC1	1.00	0.023	2.0	0.002	0.2	0.004	0.4	0.021	2.1	0.032	3.2
QC2	5.04	0.106	2.2	0.015	0.3	0.035	0.7	0.086	1.7	0.141	2.8
QC3	15.22	0.345	2.3	0.054	0.4	0.051	0.3	0.006	0.0	0.353	2.3

Reproducibility Summary of Access 2

*Default value when estimated variance was negative.

High-dose Hook Effect: The Access AMH assay demonstrated no high-dose hook effect up to 1,000 ng/mL in normal human serum spiked with recombinant AMH.

Dilution Recovery: The Access AMH assay has been demonstrated to dilute recover across the range of the assay (0 to 24 ng/mL) in plasma and serum samples. Samples containing AMH concentrations from approximately

0 - 24 ng/mL can be diluted 10-fold with an average recovery of 100 ± 10%.

Limit of Quantitation (LoQ): The Access AMH assay was designed to have a Limit of Quantitation (LOQ) of ≤ 0.08 ng/mL (0.57 pmol/L). In one study, the LoQ for Access AMH was determined to be 0.013 ng/mL (0.093 pmol/L).

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The Access AMH was designed to be linear, with a maximum deviation from linearity of ≤ 5% for samples > 0.16 Linearity: ng/mL, and ≤ 0.04 ng/mL for samples ≤ 0.16 ng/mL. One study analyzed using a polynominal regression method demonstrated a maximum deviation from linearity of 4.8% for samples > 0.16 ng/mL for samples ≤0.16 ng/mL.

		Reagent Lot470103Calibrator Lot P2Access 2 #504310		Reagent Lot470116Calibrator Lot P3Access 2 #504310		Reagent Lot470103Calibrator Lot P2Access 2 #506902		Reagent Lot470116Calibrator Lot P2Access 2 #506902		Reagent Lot470098Calibrator Lot P1Access 2 #501022		Reagent Lot470098Calibrator Lot P2Access 2 #509403
Sample	ExpectedResult(ng/mL)	ObservedResult(ng/mL)	ExpectedResult(ng/mL)	ObservedResult(ng/mL)	ExpectedResult(ng/mL)	ObservedResult(ng/mL)	ExpectedResult(ng/mL)	ObservedResult(ng/mL)	ExpectedResult(ng/mL)	ObservedResult(ng/mL)	ExpectedResult(ng/mL)	ObservedResult(ng/mL)
Sample 1	0.00	0.00	0.00	0.0025	0.00	0.00	0.01	0.005	0.004	0.004	0.004	0.004
Sample 2	3.22	3.14	3.26	3.17	2.88	3.08	2.87	3.1	3.02	2.91	3.04	2.93
Sample 3	6.44	6.18	6.51	6.10	5.76	5.82	5.73	5.86	6.04	5.97	6.08	5.93
Sample 4	9.66	9.17	9.76	9.02	8.64	8.99	8.59	9.15	9.06	8.74	9.12	8.80
Sample 5	12.88	12.57	13.02	12.29	11.52	11.86	11.45	11.87	12.08	11.54	12.17	11.92
Sample 6	16.10	15.28	16.27	15.29	14.10	14.23	14.32	14.36	15.10	14.74	15.21	14.79
Sample 7	19.32	18.45	19.52	18.79	17.28	17.39	17.18	17.67	18.12	17.94	18.26	19.30
Sample 8	22.54	21.71	22.77	22.14	20.16	20.81	20.04	20.61	21.14	21.36	21.29	21.22
Sample 9	25.75	25.76	26.03	26.03	23.04	23.30	22.90	22.90	24.16	23.80	24.33	24.46

Linearity – Expected and Observed Concentrations

Beckman Coulter Inc. Access AMH Assay Traditional 510(k) Page 6 of 11

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Analytical Specificity:

Serum samples with AMH concentrations of approximately 2 and 10 ng/mL (14.3 and 71 pmol/L) were spiked with concentrations of the substances below and run on a single Access 2 Immunoassay System. Total Protein (human serum albumin) was tested in serum samples with AMH concentrations of approximately 2 and 7 ng/mL (14.3 and 50 pmol/L). Values were calculated as described in CLSI EP7-A2. Interference was determined by testing controls (no interfering substance added) and matched test samples (with interfering substance added). There was no significant interference (exceeding 10% shift in dose) observed when the following substances were tested at the indicated concentrations.

Substance	Highest Concentration Added
Acetaminophen	20 mg/dL
Acetylsalicylic acid	65 mg/dL
Ampicillin sodium salt	1000 mg/L
Ascorbic acid	170 µmol/L
Bilirubin (Conjugated)	43 mg/dL
Bilirubin (Unconjugated)	40 mg/dL
Biotin	179 ng/mL
Cefoxitin sodium salt	2500mg/L
Cyclosporin A	5 mg/L
Doxycycline hyclate	50 mg/L
Folic acid	0.4 mg/L
Gamma Globulin	60 mg/L
Hemoglobin	1 g/dL
Heparin (low molecular weight)	3000 U/L
lbuprofen	50 mg/dL
lgA	1.8 g/dL
lgG	2.5 g/dL
IgM	0.5 g/dL
Intralipids	37 mmol/L
Levodopa	20 mg/L

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Levothyroxine sodium hydrate	0.2 mg/L
Metformin	2000 mg/L
Methyldopa	20 mg/L
Metronidazole	200 mg/L
N-Acetyl-L-cysteine	150 mg/L
Phenylbutazone	400 mg/L
Rheumatoid Factor	1000 IU/mL
Rifampicin	60 mg/L
Theophylline	100 mg/L
Triptoréline (Gonapeptyl)	0.1 mg/L
Total protein (human serum albumin)	12 g/dL
Uric Acid	1.4 mmol/L

Cross-reactivity:

Serum samples with AMH concentrations of approximately 2 and 10 ng/mL (14.3 and 71 pmol/L) spiked with concentrations of the substances below and run on a single Access 2 Immunoassay System. Activin A was tested in serum samples with AMH concentrations of approximately 1 and 5 ng/mL (7.1 and 36 pmol/L). Values were calculated per CLSI EP7-A2. There was no significant cross reactivity (exceeding 5% cross reactivity) observed when the following substances were tested at the indicated concentrations:

Cross-reactant Substance	Highest Concentration Added
Inhibin A	100 ng/mL
Activin A	16.32 $ μ $ g/L
hLH	100 mlU/mL
hFSH	115 mlU/mL
TGF β-1	65 ng/mL

Matrix Comparison: A comparison of fifty-seven (57) matched sets of serum (gel and no gel) and plasma (lithium-heparin) samples with AMH concentrations spanning as much of the assay range as practicably possible. All sample type combinations pass the specification of slope equal to 1.00 ± 0.10.

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Sample type comparison	Slope	Sample Range(ng/mL)	N
Lithium Heparin vs.SerumNo Gel	1.03	0.20 to 13.75	57
Lithium Heparin vs. SerumGel	1.05	0.19 to 13.71	57
Serum Gel vs. Serum No Gel	0.99	0.20 to 13.75	57

Method Comparison: A comparison of 121 values across the range of the assay using the Access AMH assay on the Access 2 Immunoassay system and a commercially available immunoassay kit gave the following statistical data using Passing Bablok regression and Spearman correlation for the r calculation:

N	Range ofObservations (ng/mL)	Intercept(ng/mL)	Slope(95% CI)	CorrelationCoefficient (r)
121	0.070 to 22.80	0.04	1.03 (1.01 – 1.06)	0.99

Access AMH Clinical Study: A multicenter, clinical study of 164 women was used to correlate AMH values to the antral follicle count (AFC) in women presenting to fertility clinics for evaluation. The trial enrolled women at 13 geographically diverse sites in the US who were between ≥ 21 and < 46 years of age (mean age 34.9 years, range of 23 to 45 years). The women were in their first cycle of ovarian stimulation for IVF or IVF/ICSI, with both ovaries present and a reqular menstrual cycle, and without confirmed polycystic ovary syndrome (PCOS). The mean body mass index (BMI) of all participating women averaged 25.1 with a standard deviation of ± 5.3. The AFC result was determined by transvaginal ultrasonography, which measured follicles of 2 to 10 mm in diameter. The AFC and AMH were determined on days 2 - 4 of the same spontaneous menstrual cycle. The trial demonstrated that the AMH levels measured for these subjects (N) correlate well with the AFC results (r = 0.77, p < 0.0001).

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The AFC results were sorted into 2 groups: ≤ 15 (67%) or > 15 (33%). For the > 15 AFC group the AMH cutoff is 1.77 ng/mL. The corresponding sensitivity and specificity were 88.9% and 59.1%, respectively. For patients with an AMH concentration that was > 1.77 ng/mL, 52% were in the > 15 AFC group and 48% were in the ≤ 15 AFC group. The study results support the system can distinguish between women with AFC values > 15 (high ovarian reserve) and women with AFC values ≤ 15 (normal or diminished ovarian reserve).

Expected Reference Intervals: The serum and plasma samples were prospectively procured from apparently healthy, non-pregnant females at five (5) geographically diverse sites. Subjects were required to have regular menstrual cycles between 21 and 35 days, both ovaries present, and proven fertility. Populations studied are described by group in the table below.

Serum AMH
Group (years)	Sample Size	Median ng/mL(pmol/L)	95% Reference Intervalng/mL (pmol/L)
18-25	120	3.6(25.70)	1.02 - 14.63(7.28 - 104.46)
26-30	131	3.82(27.27)	0.69 - 13.39(4.93 - 95.60)
31-35	120	2.47(17.64)	0.36 - 10.07(2.57 - 71.90)
36-40	123	1.71(12.21)	0.18 - 5.68(1.29 - 40.56)
41-45	126	0.54(3.86)	0.01 - 2.99(0.07 - 21.35)

{14}------------------------------------------------

Plasma AMH
Group (years)	Sample Size	Median ng/mL(pmol/L)	95% Reference Intervalng/mL (pmol/L)
18-25	120	3.75(26.78)	1.04 - 15.25(7.43 - 108.89)
26-30	131	4.06(28.99)	0.74 - 13.81(5.28 - 98.60)
31-35	120	2.56(18.28)	0.38 - 10.50(2.71 - 74.97)
36-40	123	1.78(12.71)	0.19 - 6.06(1.36 - 43.27)
41-45	126	0.56(4.00)	0.01 - 3.17(0.07 - 22.63)

Conclusion:

The conclusions drawn from the nonclinical and clinical testing demonstrate that the Access AMH assay for use on the Access Immunoassay Systems, are as safe, as effective, and performs as well as the predicate.

Regulation Number and Section

§ 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.