The Access Estradiol assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of estradiol levels in human serum, using the Access Immunoassay System.

Device Description

The Access® Estradiol reagents and the Access® Immunoassay Analyzer comprise the Access® Immunoassay System for the quantitative determination of Estradiol levels in human serum.

AI/ML Overview

This document describes the validation of the ACCESS® Estradiol assay, an immunoassay for determining estradiol levels in human serum.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the device are implied by the "Summary of Studies" section, where specific performance metrics are reported. There are no explicit "acceptance criteria" stated as thresholds; rather, the study presents the observed performance and concludes that the device is substantially equivalent to a predicate device.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Precision (Within Run)	CV within acceptable clinical ranges for estradiol measurement	Ranges from 19.7% CV (at 39 pg/ml) to 3.1% CV (at 2167 pg/ml)
Precision (Total)	CV within acceptable clinical ranges for estradiol measurement	Ranges from 20.0% CV (at 39 pg/ml) to 5.0% CV (at 2918 pg/ml)
Accuracy (Spiking Recovery)	Recovery between 80% and 120%	Ranging from 80% to 115%
Accuracy (Dilution Recovery)	Mean recovery close to 100%	Mean recoveries of 108% to 112%. Average dilution recovery at 1:2 was 106%. For samples >500 pg/ml, average % recovery was 107%.
Correlation with Predicate Device	Strong positive correlation (e.g., r > 0.95)	r = 0.98
Analytical Sensitivity (Lowest Detectable Level)	Detectable level at or below clinically relevant thresholds	20 pg/ml
Analytical Specificity (Cross-Reactivity with Estrone Sulfate)	Negligible or no detectable cross-reactivity	Not detectable when spiked at 3600 pg/ml
Analytical Specificity (Cross-Reactivity with Estriol Sulfate)	Low percentage apparent cross-reactivity	Apparent cross-reactivity of 0.004% when spiked at 10,000,000 pg/ml

Study Details

Sample sizes used for the test set and the data provenance:
- Precision studies: The number of samples for precision studies is not explicitly stated, but typically involves multiple replicates of several control levels or patient samples. The data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Accuracy (Spiking recovery): Ten serum samples were used. Data provenance not specified.
- Accuracy (Dilution recovery): 2 patient samples and 2 patient pools were used, along with 10 patient samples with estradiol >500 pg/ml. Data provenance not specified.
- Correlation: 103 samples were run. Data provenance not specified.
- Analytical Sensitivity: Implies samples were used to determine the lowest detectable level. Number of samples not specified.
- Analytical Specificity: S0 calibrator was spiked with estriol sulfate and estrone sulfate. Number of samples/spiked conditions not explicitly detailed beyond the two substances.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is an in vitro diagnostic (IVD) device (immunoassay). The "accuracy" and "sensitivity" of such devices are typically established against reference methods or through spiked samples with known concentrations, rather than through expert consensus on images or clinical conditions. Therefore, the concept of "experts establishing ground truth for the test set" in the context of interpretation of results (like in image analysis) does not directly apply here. The "ground truth" for quantitative measurements like estradiol is the actual concentration determined by highly accurate methods (e.g., mass spectrometry, or certified reference materials) or by the known concentration of spiked analytes. The document does not specify details about these reference methods or expert panel for ground truth.
Adjudication method for the test set:
Not applicable (N/A) for this type of quantitative immunoassay study. Adjudication methods like 2+1 or 3+1 are typically used for qualitative or interpretive assessments, such as in image reading where multiple experts might disagree on findings. Here, results are quantitative values compared to known or reference values.
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 (N/A). This is an immunoassay, not an AI-assisted diagnostic tool involving human readers interpreting cases.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, this is implicitly a standalone study. The performance characteristics (precision, accuracy, sensitivity, specificity, correlation) are reported for the ACCESS® Estradiol assay system itself (reagents + analyzer) as a device, independent of human interpretation or intervention in the measurement process beyond operating the instrument and following procedures.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth used here consists of:
- Known concentrations: For spiking recovery studies (estradiol spiked into serum samples) and analytical specificity studies (estrone sulfate, estriol sulfate spiked into calibrator).
- Reference measurements: The Abbott IMx® Estradiol Kit served as a comparator for the correlation study, implying it was considered a widely accepted and validated method for measuring estradiol. For precision and dilution recovery, the ground truth is the inherent concentration of estradiol in the samples, measured multiple times or diluted to known proportions.
The sample size for the training set:
Not applicable (N/A) as this is a traditional immunoassay validation report, not one describing a machine learning or AI-driven device that requires a distinct "training set." The development of the assay itself involves optimization and characterization over many samples, but these are not formally called "training sets" in the context of this type of document.
How the ground truth for the training set was established:
Not applicable (N/A). See point 7.

Summary

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APPENDIX 4

K973743

Summary of Safety and Effectiveness Information

September 30, 1997

1. General Information		OCT 31 1997
Device Generic Name:	Enzyme Immunoassay, Estradiol
Device Trade Name:	ACCESS® Estradiol assay
Applicant's Name and Address:	Beckman Instruments, Inc.1000 Lake Hazeltine DriveChaska, MN 55318	Contact: Robert McCormack, Ph.D.612-368-1384

Predicate Device 2.

Abbott IMx® Estradiol Kit Abbott Laboratories Diagnostics Division Abbott Park, IL 94547

3. Device Description

The Access® Estradiol reagents and the Access® Immunoassay Analyzer comprise the Access® Immunoassay System for the quantitative determination of Estradiol levels in human serum.

4. Indications for Use

The Access® Estradiol assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of Estradiol levels in human serum using the Access® Immunoassay System.

Comparison of Technological Characteristics 5.

The Access® Estradiol assay and the Abbott IMx® Estradiol Kit are for the measurement of estradiol in human serum. Both tests utilize polyclonal rabbit antibodies for capture and an alkaline phosphatase conjugate. Both tests use multi-point liquid calibrators. The Access® Estradiol assay uses a dioxetane based chemiluminescent substrate while the Abbott IMx® Estradiol Kit uses 4methylumbelliferyl phosphate as the substrate. The Access® Estradiol assay measures light production from a chemiluminescent reaction, while the Abbott IMx® Estradiol Kit measures a fluorescent product. The Access® Estradiol assay uses calibrators prepared in a human serum matrix while the Abbott IMx® Estradiol Kit uses calibrators prepared in Tris buffer with protein stabilizers. The Access® Estradiol assay uses a competitive assay format with a delayed conjugate addition while the Abbott IMx® Estradiol Kit uses a sequential assay format.

6. Summary of Studies

Precision studies: Within run precision ranges from 19.7% CV (39 pg/ml) to 3.1% CV (2167 pd/ml). Total imprecision ranges from 20.0% CV (39 pg/ml) to 5.0% CV (2918 pg/ml).

Accuracy: Spiking recovery studies performed by spiking estradiol into ten serum samples results in recovery ranging from 80% to 115%. Dilution recovery studies performed by diluting 2 patient samples and 2 patient pools from 1:2 to 1:8 with Estradiol Calibrator S0 results in a mean recoveries of 108% to 112%. The average dilution recovery at 1:2 was 106%. In addition, 10 patient samples with estradiol >500 pg/ml were diluted 1:2 with S0 with an average % recovery of 107%.

Correlation: A comparison of estradiol values from 103 samples run in both the Access® Estradiol assay and the Abbott IMx® Estradiol Kit test gives the following statistical data: r= 0.98.

Analytical Sensitivity: The data supports the lowest detectable level of estradiol distinquishable from zero (Estradiol Calibrator S0) as 20 pq/ml.

Analytical Specificity: Estrone sulfate is not detectable when spiked into the S0 calibrator at 3600 pg/ml. Estriol sulfate gives an apparent cross reactivity of 0.004% when spiked into the S0 calibrator at 10,000,000 pg/ml.

7. Conclusion

The Access® Estradiol reagents when used with the Access® Immunoassay Analyzer are substantially equivalent to another test for the measurement of estradiol levels now in commercial distribution.

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Image /page/1/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the circle is an abstract symbol that resembles a stylized human figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 3 1 1997

Michele Z. Burtness Regulatory Specialist Beckman Instruments, Inc. 100 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

Re: K973743 ACCESS® Estradiol Assay Regulatory Class: I, II Product Code: CHP, JIS September 30, 1997 Dated: Received: October 1, 1997

Dear Ms. Burtness:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate abe beat 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diaqnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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R 1: i

INDICATIONS FOR USE STATEMENT

510(k) Number ( if known): ___________________________________________________________________________________________________________________________________________________ K973743

Device Name: ACCESS® Estradiol Reagents on the ACCESS® Immunoassay Analyzer

indications For Use:

The Access Estradiol assay is a paramagnetic particle, chemiluminescent immunoassay for the oventuative determination of estradiol levels in human serum, using the Access Immunoassay System.

SUMMARY AND EXPLANATION

Estradiol (17b - estradiol, 1,3,5 (10) - Estratrien - 3,17b - diol) is a natural estrogen with a motecular mass of 272.3 daltons. Most circulating estradiol is bound to protein. It is estimated that one 1-3% of serum estradiol is free (unbound). In non-pregnant women, estradiol is secreted by overy and the corpus luteum. The adrenals and testes (in men) are also believed to secrete minute amounts of estradiol (1). Estradiol levels are lowest at menses and into the early follicular phase and rise in the late follicular phase to a peak just prior to the hLH (human Luteinizing Hornone) surge, initiating ovulation. As the hLH peaks, the levels of estradiol decrease before nong again in the luteal phase. Endometrial growth is stimulated by estradiol and progesterone ( croted by the corpus luteum) in preparation for implantation of a fertilized egg. If conception doos not occur, the secretion of estradiol and progesterone by the corpus luteum decreases, intisting menses (2).

Lovels of estradiol are useful in monitoring ovulatory status. Because estradiol levels reflect folicular maturation, the measurement of estradiol is a valuable tool in the assessment of sexual development, etiology of amenorrhea, causes of infertility and menopause (3,4). Abnormally high levels in males are indicative of feminizing syndromes such as gynecomastia (5).

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Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory evices
510(k) Number. K973743

110 - 1 - M3/M5

Regulation Number and Section

§ 862.1260 Estradiol test system.

(a)
Identification. An estradiol test system is a device intended to measure estradiol, an estrogenic steroid, in plasma. Estradiol measurements are used in the diagnosis and treatment of various hormonal sexual disorders and in assessing placental function in complicated pregnancy.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.