ACCESS ESTRADIOL REAGENTS ON THE ACCESS IMMUNOASSAY ANALYZER

K973743 · Beckman Instruments, Inc. · CHP · Oct 31, 1997 · Clinical Chemistry

Device Facts

• Record ID: K973743
• Device Name: ACCESS ESTRADIOL REAGENTS ON THE ACCESS IMMUNOASSAY ANALYZER
• Applicant: Beckman Instruments, Inc.
• Product Code: CHP · Clinical Chemistry
• Decision Date: Oct 31, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1260
• Device Class: Class 1

Intended 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.

Device Story

The Access Estradiol assay is a paramagnetic particle chemiluminescent immunoassay used with the Access Immunoassay System to quantify estradiol in human serum. The device utilizes polyclonal rabbit antibodies for capture and an alkaline phosphatase conjugate in a competitive assay format with delayed conjugate addition. The system measures light production from a chemiluminescent reaction using a dioxetane-based substrate. It is intended for use in clinical laboratory settings by trained personnel. By providing quantitative estradiol measurements, the device assists clinicians in assessing follicular maturation, ovulatory status, and various endocrine conditions, thereby supporting clinical decision-making regarding fertility, menopause, and hormonal disorders.

Clinical Evidence

Bench testing only. Precision studies showed within-run CVs of 3.1% to 19.7% and total imprecision of 5.0% to 20.0%. Accuracy was validated via spiking recovery (80-115%) and dilution recovery (106-112%). Correlation with the predicate device (n=103) yielded r=0.98. Analytical sensitivity (lowest detectable level) is 20 pg/ml. Analytical specificity testing showed negligible cross-reactivity with estrone sulfate and estriol sulfate.

Technological Characteristics

Paramagnetic particle chemiluminescent immunoassay. Uses polyclonal rabbit antibodies and alkaline phosphatase conjugate. Competitive assay format. Dioxetane-based chemiluminescent substrate. Multi-point liquid calibrators in human serum matrix. Automated system (Access Immunoassay System).

Indications for Use

Indicated for the quantitative determination of estradiol levels in human serum to monitor ovulatory status, assess sexual development, investigate etiology of amenorrhea, evaluate causes of infertility and menopause, and identify feminizing syndromes in males.

Regulatory Classification

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.

Predicate Devices

• Abbott IMx® Estradiol Kit

Submission Summary (Full Text)

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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.<br>1000 Lake Hazeltine Drive<br>Chaska, MN 55318 | Contact: Robert McCormack, Ph.D.<br>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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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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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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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# 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

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