(57 days)
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 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 Access Anti-Mullerian Hormone Assay, Access Anti-Mullerian Hormone Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay System for the quantitative determination of Anti-Mullerian Hormone levels in human serum and lithium heparin plasma using the Dxl 9000 Access Immunoassay system.
The provided text describes the performance of the Access AMH assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to a predicate device (Access AMH assay on Access 2 Immunoassay System).
Here's an analysis of the acceptance criteria and study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a single table outlining acceptance criteria for all aspects, but rather describes them within the "Summary of Studies" section. Based on the text, here's a reconstructed table:
| Test Parameter | Acceptance Criteria | Reported Device Performance (Access AMH on Dxl 9000) | Result |
|---|---|---|---|
| Method Comparison | Not explicitly stated (implied to be comparable) | Slope: 1.02 (95% CI: 1.00 - 1.03) Intercept: 0.011 (95% CI: -0.013 - 0.067) Correlation Coefficient (R): 1.00 | Comparable to predicate device; estimated bias at reference limits hasn't changed appreciably. |
| Imprecision | Within-laboratory (total) %CV for AMH concentrations > 0.16 ng/mL | Within-laboratory (total) %CV ranged from 2.2% to 5.4% for AMH concentrations > 0.16 ng/mL. Maximum Total Error (TE) of 16% (meets acceptance criteria) | Meets acceptance criteria for total error and bias. |
| Linearity | Linear throughout the analytical measuring interval. | Linear on the Dxl 9000 Immunoassay System throughout the analytical measuring interval (0.08 - 24 ng/mL (0.57 - 171 pmol/L)). | Meets acceptance criterion. |
| Limit of Blank (LoB) | ≤ 0.01 ng/mL | Determined to be 0.001 ng/mL. | Meets acceptance criterion. |
| Limit of Detection (LoD) | ≤ 0.02 ng/mL | Estimated to be 0.002 ng/mL. | Meets acceptance criterion. |
| Limit of Quantitation (LoQ) | ≤ 0.08 ng/mL (0.57 pmol/L) for 20% within-laboratory (total) CV | The 20% CV LoQ estimate is 0.003 ng/mL (0.02 pmol/L). The LoQ at 20% within-laboratory (total) CV estimate is ≤ 0.08 ng/mL (0.57 pmol/L). | Meets acceptance criterion. |
| Reproducibility | SD ≤ 0.042 ng/mL for values ≤ 0.16 ng/mL CV ≤ 13.0% for values > 0.16 ng/mL | The study (data not explicitly presented in detail beyond the conclusion) shows that the Access AMH assay meets design input requirements for reproducibility on Dxl 9000 with an SD ≤ 0.042 ng/mL for values ≤ 0.16 ng/mL and CV ≤ 13.0% for values > 0.16 ng/mL. | Meets design input requirements. |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison:
- Sample Size: N = 126
- Data Provenance: Not specified (e.g., country of origin, retrospective/prospective). The "Concentration Range" is specified as "Access 2 values," suggesting that these are samples previously run on the predicate device.
- Imprecision:
- Sample Size: 88 for each of the 9 samples tested (total 9 x 88 = 792 individual measurements).
- Data Provenance: Not specified.
- Linearity, LoB, LoD, LoQ, Reproducibility:
- Sample Size: Not explicitly stated for these individual studies, beyond the "N" values in the imprecision table.
- Data Provenance: Not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document describes performance characteristics of an in vitro diagnostic (IVD) assay quantifying AMH levels. Ground truth in this context typically refers to the true concentration of AMH in a sample, often established by a reference method or highly accurate assay.
- The text does not mention the use of human experts (e.g., radiologists) or their qualifications to establish ground truth for the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility).
- For these types of IVD studies, the "ground truth" is often established by comparing the device's results to a recognized reference method or the established predicate device, or by using validated calibrators and controls with known analyte concentrations.
4. Adjudication Method for the Test Set
Given that this is an in vitro diagnostic device assessing analytical performance rather than diagnostic imaging interpretation, an adjudication method (like 2+1 or 3+1) is not applicable and therefore not mentioned. The evaluation relies on quantitative measurements against analytical criteria or a comparative method.
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
- No, an MRMC comparative effectiveness study was not done.
- This device is an in vitro diagnostic test for Anti-Müllerian hormone (AMH) levels, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of improving human reader performance with AI assistance is not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, the provided studies describe standalone performance of the assay.
- The Access AMH assay is an automated chemiluminescent immunoassay run on an analyzer (Dxl 9000 Access Immunoassay Analyzer). The performance metrics (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility) are inherently standalone, reflecting the analytical capabilities of the device itself without direct human interaction in the measurement process (beyond operating the instrument and collecting/inputting samples).
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- For the analytical performance studies (method comparison, imprecision, linearity, LoB, LoD, LoQ, reproducibility), the ground truth is implicitly defined by:
- Reference method/Predicate device comparison: For the method comparison study, the "Access 2 values" (from the predicate device) serve as the reference point for comparison.
- Known concentrations: For imprecision, linearity, LoB, LoD, LoQ studies, ground truth is established using samples (e.g., controls, calibrators, spiked samples) with known or carefully characterized AMH concentrations. This is a common practice in IVD analytical validation.
- It is not based on expert consensus, pathology, or outcomes data, as these are typically used for clinical diagnostic accuracy studies or imaging interpretation.
8. The Sample Size for the Training Set
The document describes performance validation studies, not development studies involving a training set in the context of machine learning.
- Therefore, the concept of a "training set" in this context is not applicable as this is an immunoassay, not an AI/ML algorithm that requires training data.
9. How the Ground Truth for the Training Set was Established
As mentioned above, the concept of a "training set" is not applicable. Therefore, there is no discussion of how ground truth for a training set was established.
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February 3, 2023
Beckman Coulter, Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318
Re: K223679
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: December 8, 2022 Received: December 8, 2022
Dear Kate Oelberg:
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
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) 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
Digitally signed by Paula
Caposino -S
Caposino -S
Date: 2023.02.03 17:08:40
-05'00'
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
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Indications for Use
510(k) Number (if known) K223679
Device Name Access AMH
Indications for Use (Describe)
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 therapy. The Access AMH is not intended to be used for monitoring of women undergoing controlled ovarian stimulation in an Assisted Reproduction Technology program.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Access AMH 510(k) Summary
510(k) Summary
510(k) Number K223679
Date Prepared: February 3, 2023
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92
The assigned 510(k) number is K223679.
Submitted By:
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
Primary Contact:
Kate Oelberg Senior Staff Quality and Regulatory Affairs Phone: (612) 431-7315 Email: kmoelberg@beckman.com
Alternate Contact:
Madhuri Boppana Regulatory Affairs Analyst, Senior Email: mboppana@beckman.com
Device Name:
Common Name: Anti-Müllerian hormone test system Trade Name: Access AMH Classification Name: Anti-Müllerian hormone test system Classification Regulation: (21 CFR 862.1092)
Predicate Device: Device Name: Access AMH 510(k) Numbers: K170524
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Device Description
The Access Anti-Mullerian Hormone Assay, Access Anti-Mullerian Hormone Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay System for the quantitative determination of Anti-Mullerian Hormone levels in human serum and lithium heparin plasma using the Dxl 9000 Access Immunoassay system.
Intended Use
The Access AMH assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of anti-Mullerian 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.
| Parameter | Access AMH Assay on Access2 Immunoassay SystemPredicate - K170524 | Access AMH Assay on Dxl 9000Access Immunoassay Analyzer |
|---|---|---|
| Intended use | The Access AMH assay is aparamagnetic particlechemiluminescent immunoassayfor the quantitative determinationof anti-Müllerian hormone (AMH)levels in human serum andlithium heparin plasma using theAccess Immunoassay Systemsas an aid in the assessment ofovarian reserve in womenpresenting to fertility clinics.This system is intended to | Same |
| Parameter | Access AMH Assay on Access2 Immunoassay SystemPredicate – K170524 | Access AMH Assay on Dxl 9000Access Immunoassay Analyzer |
| distinguish between womenpresenting with AFC (antralfollicle count) values >15 (highovarian reserve) and womenwith AFC values ≤15 (normal ordiminished ovarian reserve). TheAccess AMH is intended to beused in conjunction with otherclinical and laboratory findingssuch as antral follicle count,before starting fertility therapy.The Access AMH is not intendedto be used for monitoring ofwomen undergoing controlledovarian stimulation in anAssisted ReproductionTechnology program. | ||
| AnalyteMeasured | Anti-Müllerian hormone (AMH)levels in human serum andlithium heparin plasma | Same |
| Technology | Two-site immunoenzymatic(sandwich) assay | Same |
| Format | Chemiluminescent | Same |
| Method | Automated | Same |
| Calibration | Utilizes a stored calibrationcurve | Same |
| Sample Type | Serum or plasma | Same |
| Reagent Packformulation andpackaging | Access Reagent Packformulation and packaging. | Same |
| MeasuringRange | 0.08-24 ng/mL (0.57-171pmol/L). | Same |
| ReagentStability | Unopened at 2° to 10°C untilstated expiration date | Same |
| Substrate | Access Substrate | Lumi-Phos PRO Substrate |
| Instrument | Access 2 Immunoassay system | Dxl 9000 Access ImmunoassayAnalyzer |
Comparison of Technological Characteristics to the Predicate
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Summary of Studies
Method Comparison: The results of the Access AMH assay on the Dxl 9000 are comparable to those of the Access AMH assay on Access 2. Further, the estimated bias at concentrations corresponding to reference limits defined on the predicate system suggest that such values have not changed appreciably on the Dxl 9000 system.
| N | ConcentrationRange* (ng/mL) | Slope | Slope95% CI | Intercept | Intercept95% CI | CorrelationCoefficientR |
|---|---|---|---|---|---|---|
| 126 | 0.11 - 22 | 1.02 | 1.00 - 1.03 | 0.011 | -0.013 -0.067 | 1.00 |
*Range is Access 2 values
Imprecision: The within-laboratory (total) % CV ranged from 2.2% to 5.4%, for AMH concentrations > 0.16 ng/mL. Access AMH Advanced assay meets total error and bias acceptance criteria with maximum Total Error (TE) of 16%.
| ng/mL | Repeatability(Within-Run) | Between-Run | Between-Day | Within-Laboratory | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 88 | 0.29 | 0.010 | 3.6 | 0.006 | 2.0 | 0.006 | 2.0 | 0.013 | 4.6 |
| Sample 2 | 88 | 0.80 | 0.030 | 3.7 | 0.000 | 0.0 | 0.000 | 0.0 | 0.030 | 3.7 |
| Sample 3 | 88 | 1.0 | 0.03 | 3.0 | 0.02 | 2.1 | 0.03 | 3.0 | 0.05 | 4.8 |
| Sample 4 | 88 | 2.4 | 0.11 | 4.5 | 0.00 | 0.0 | 0.05 | 2.0 | 0.12 | 5.0 |
| Sample 5 | 88 | 5.1 | 0.18 | 3.4 | 0.03 | 0.7 | 0.09 | 1.7 | 0.20 | 3.9 |
| Sample 6 | 88 | 6.9 | 0.19 | 2.8 | 0.00 | 0.0 | 0.16 | 2.3 | 0.25 | 3.6 |
| Sample 7 | 88 | 13 | 0.4 | 3.1 | 0.3 | 1.9 | 0.3 | 2.6 | 0.6 | 4.5 |
| Sample 8 | 88 | 16 | 0.7 | 4.4 | 0.0 | 0.0 | 0.5 | 3.1 | 0.8 | 5.4 |
| Sample 9 | 88 | 19 | 0.5 | 2.6 | 0.3 | 1.8 | 0.3 | 1.4 | 0.6 | 3.4 |
Linearity: The results of this study met the acceptance criterion and indicate that the Access AMH assay is linear on the Dxl 9000 Immunoassay System throughout the analytical measuring interval (0.08 - 24 ng/mL (0.57 - 171 pmol/L).
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Limit of Blank (LoB): The LoB for AMH was determined to be 0.001 ng/mL on the Dxl 9000 Immunoassay System. The results of this study demonstrate that the AMH assay met the acceptance criterion of ≤ 0.01 ng/mL.
Limit of Detection (LoD): The LoD estimate for the AMH assay is 0.002 ng/mL on the Dxl 9000 Immunoassay System. The results of this study demonstrate that the AMH assay met the acceptance criterion of ≤ 0.02 ng/mL on the Dxl 9000 Access Immunoassay System.
Limit of Quantitation (LoQ): The results provided demonstrate the 20% CV LoQ estimate for the Access AMH assay is 0.003 ng/mL (0.02 pmol/L). The results provided demonstrate the LoQ at 20% within-laboratory (total) CV estimate of the Access AMH assay to be ≤ 0.08 ng/mL (0.57 pmol/L).
Reproducibility: The study shows that the Access AMH assay meets design input requirements for reproducibility on Dxl 9000 with an SD ≤ 0.042 ng/mL for values ≤ 0.16 ng/mL and CV ≤ 13.0% for values > 0.16 ng/mL.
Conclusion: The information provided in this submission demonstrates that the proposed new device is substantially equivalent to the predicate device.
§ 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.