K Number
K040181
Date Cleared
2004-03-24

(57 days)

Product Code
Regulation Number
862.1245
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Access DHEA-S assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative measurement of dehydroepiandrosterone sulfate levels in human serum and plasma using the Access Immunoassay Systems.

Measurement of dehydroepiandrosterone sulfate may be used in the differential diagnosis of Cushing's syndrome as well as in the evaluation of adrenocortical diseases, congenital adrenal hyperplasia, and adrenal tumors. In hirsute female patients, increased DHEA-S levels have been associated with virilizing adrenal tumors. Patients with polycystic ovary syndrome have often demonstrated elevated levels of DHEA-S, with persons overall androgen contribution to the defect in this disorder.

The Access DHEA-S Calibrators are intended to calibrate the Access DHEA-S assay for the quantitative determination of Dehydroepiandrosterone sulfate levels in human serum and plasma using the Access Immunoassay Systems.

Device Description

The Access® DHEA-S Reagent is designed for optimal performance on the Access family of Immunoassay Systems, including the Access 2, UniCel Dxl and UniCel DxC Systems. The Access Immunoassay Systems utilize a competitive binding immunoassay for quantitative analyte measurement. The Access DHEA-S Reagent is packaged in two 50-test reagent packs and is packaged separately from the associated calibrators. The Access DHEA-S Calibrators are designed for use with the Access DHEA-S Reagent for generation of the Access calibration curve on Access Immunoassay Systems. The Access calibrators are packaged in 5.0 mL bottles, one for each of six calibrator levels.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access® DHEA-S Reagent and Calibrators, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly state formal "acceptance criteria" with numerical targets for each performance parameter. Instead, it presents performance data and implies that these results were considered sufficient for substantial equivalence. The comparison is made against a legally marketed predicate device (Immulite DHEA-SO4 Reagent).

Performance MeasureAcceptance Criteria (Implied)Reported Device Performance (Access DHEA-S)Predicate Device (Immulite DHEA-SO4)
Method ComparisonStrong correlation with predicate (r close to 1) and a slope close to 1 with minimal intercept.Slope: 1.028N/A (predicate for comparison)
Intercept: 6.6N/A (predicate for comparison)
r (correlation coefficient): 0.993N/A (predicate for comparison)
Analytical SensitivityPerformance comparable to or better than predicate.2 µg/dL3 µg/dL
Reportable RangePerformance comparable to or better than predicate.2 - 1000 µg/dL15-1000 µg/dL
Within-Run ImprecisionLow coefficient of variation (%C.V.) across different concentration levels.Level 1 (10.3 µg/dL): 8.3% C.V.Not explicitly stated for predicate in summary
Level 2 (34.4 µg/dL): 3.2% C.V.
Level 3 (123.9 µg/dL): 4.8% C.V.
Level 4 (347.3 µg/dL): 2.6% C.V.
Level 5 (736.1 µg/dL): 1.6% C.V.
Total ImprecisionLow coefficient of variation (%C.V.) across different concentration levels.Level 1 (10.3 µg/dL): 11.3% C.V.Not explicitly stated for predicate in summary
Level 2 (34.4 µg/dL): 5.1% C.V.
Level 3 (123.9 µg/dL): 6.4% C.V.
Level 4 (347.3 µg/dL): 4.4% C.V.
Level 5 (736.1 µg/dL): 3.7% C.V.

2. Sample Size Used for the Test Set and Data Provenance

  • Sample Size (Method Comparison): 263
  • Data Provenance: Not explicitly stated in the summary (e.g., country of origin, retrospective or prospective). It is generally assumed that such studies for 510(k) submissions use prospectively collected samples or well-characterized retrospective samples.
  • Sample Size (Imprecision): 80 for each of the 5 levels tested, for both within-run and total imprecision. The "N" column likely refers to the number of replicates or measurements performed for each level.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not applicable to this type of device (in vitro diagnostic for quantitative analyte measurement). The "ground truth" for chemical assays like this is typically established by reference methods or validated laboratory measurements, not by expert consensus or review of images.

4. Adjudication Method for the Test Set

This information is not applicable for this type of device. Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective interpretation, such as imaging studies, to resolve discrepancies between readers. This device measures a quantitative biochemical marker.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

This information is not applicable to this device. This is an in vitro diagnostic assay, not an AI-based interpretation tool for human readers. Therefore, there are no "human readers" to improve with AI assistance in the context of this submission.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This information is not applicable in the AI sense. The device itself is a standalone assay system (reagent and calibrators used with an automated analyzer). Its performance is evaluated independently of human interpretation, but it's not an "algorithm" in the modern AI sense.

7. The Type of Ground Truth Used

For method comparison, the "ground truth" or reference values were generated by the predicate device (Immulite DHEA-SO4 Assay). For imprecision, the "ground truth" is derived from statistical analysis of repeated measurements of known concentration levels. It is based on analytical measurements of DHEA-S levels.

8. The Sample Size for the Training Set

The 510(k) summary does not specify a separate "training set" sample size. For an IVD like this, validation studies typically involve a single test set to demonstrate performance characteristics such as method comparison, linearity, and imprecision. While reagent formulation and assay development would involve internal optimization, it is not referred to as a "training set" in the context of this regulatory submission, nor are its details typically provided for the public summary.

9. How the Ground Truth for the Training Set Was Established

Since a "training set" is not explicitly mentioned or relevant in the context of this 510(k) summary for an IVD, the ground truth establishment for it is not described. For the performance evaluation that is reported, the ground truth is established by either the predicate device (for method comparison) or by repeated measurements of known samples (for imprecision).

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KO40181

510(k) Summary

Submitted By: 1.0

Mary Beth Tang Staff Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kraemer Blvd. W-104 Brea, CA 92822-8000 Telephone: (714) 961-3777 FAX: (714) 961-4123

Date Submitted 2.0

January 26, 2004

Device Name(s): 3.0

Proprietary Names 3.1 Access® DHEA-S Reagent Access® DHEA-S Calibrators

Classification Names 3.2 3.2 Calibrator (21 CFR § 862.1150)

Legally Marketed Device 4.0

Candidate(s)PredicateManufacturerDocketNumber
Access DHEA-S ReagentImmulite DHEA-SO4ReagentDiagnostic Products,Corp.*K935806
Access DHEA-SCalibratorsAccess Ultrasensitive hGHCalibratorsBeckman Coulter, Inc.K003098

*Diagnostic Products, Corp., Los Angeles, CA

** Beckman Coulter, Inc., Chaska, MN

Device Description 5.0

The Access® DHEA-S Reagent is designed for optimal performance on the Access family of The Access® DriEA-S Reagent is dosigned or op. Access 2, Unicel Parties Comments Createms utilize a ന്നീധിരക്ടാം Systems, Indusing The Access Immunoassay Systems utilize and SYNCHRON EX® T25 Gilnoar andiyEstor the for quantitative analyte measurement. compellive biriding inimalloonizments two 50-test reagent packs and is packaged The Access DHEA-S Calibrators are separately from the associated calibrators. separately "Iron" the "disociation" call:a.ler" of the DHEA-S Reagent for generation of the Access designed for use with the Access Britiz's Access Immunoassay Systems. The Access callbration curve 'or 'Bookman' '60 mL bottles, one for each of six calibrator levels.

Intended Use 6.0

The Access DHEA-S assay is a paramagnetic particle, chemiluminescent inhumor The Access DrilLA-0 assay is a paramaghotic parantosterone sulfate levels in human serum and plasma using the Access Immunoassay Systems. The Access DHEA-S Selum and prasma using the Access DHEA-S assay for the quantitative Calibrators are intended to oalbrate the Research in human serum and plasma using the Access Immunoassay Systems.

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Comparison to the Predicate 7.0

The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary:

Access DHEA-SReagentSimilarities
Intended UseSame as Diagnostic Products
MethodologyImmulite DHEA-SO4 Reagent
Antibody source (rabbit)
Chemiluminescent substrate
Liquid-stable reagents
Differences
Sample TypeDHEA-S: Serum, PlasmaDHEA-SO4: Serum
Sample VolumeDHEA-S: 10 µLDHEA-SO4: 5 µL
Reportable RangeDHEA-S: 2 - 1000 µg/dLDHEA-SO4: 15-1000 µg/dL
Analytical SensitivityDHEA-S: 2 µg/dLDHEA-SO4: 3 µg/dL
Calibrator MatrixDHEA-S: Liquid-stableDHEA-SO4: Lyophillized
Calibration SchemeDHEA-S: 6-point curveDHEA-SO4: 2-point adjustment

The Access DHEA-S Calibrators and the predicate calibrator utilize the same test methodology specific to Access Immunoassay Systems. Each calibrator is intended for use in a different analyte test system. Both calibrators are derived from a stabilized bovine serum albumin preparation. The Access DHEA-S Calibrators are liquid stable while the predicate calibrator is lyophilized and requires preparation.

8.0 Summary of Performance Data

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Assay equivalence is demonstrated through method comparison, linearity, and imprecision experiments.

Access DHEA-S Method Comparison Study Results
Candidate MethodSlopeInterceptrnPredicate Method
Access DHEA-S Assay1.0286.60.993263Immulite DHEA-SO4 Assay
SampleMean (µg/dL)S.D. (µg/dL)%C.V.N
Within-Run Imprecision
Level 110.30.868.380
Level 234.41.103.280
Level 3123.95.904.880
Level 4347.38.922.680
Level 5736.112.101.680
Total Imprecision
Level 110.31.1611.380
Level 234.41.765.180
Level 3123.97.996.480
Level 4347.315.404.480
Level 5736.127.203.780

Access DHEA-S Estimated Imprecision

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/2/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of three human figures.

MAR 2 4 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Mary Beth Tang Staff Regulatory Affairs Specialist Beckman Coulter, Inc. 200 S. Kaemer Blvd., W-104 P.O. Box 8000 Brea, California 92822-8000

Re: K040181

Trade/Device Name: Access® DHEA-S Reagent and Calibrators Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIT: JKC Dated: January 26, 2004 Received: January 27, 2004

Dear Ms. Tang:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the . Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K040181

Device Name: Access® DHEA-S Reagent and Calibrators

Indications For Use:

The Access DHEA-S assay is a paramagnetic particle, chemiluminescent immunoassay The Access DFIEA O doody is a para. Regiveroepiandrosterone sulfate levels in human serum and plasma using the Access Immunoassay Systems.

Measurement of dehydroepiandrosterone sulfate may be used in the differential Measurement of "donyarooplanars well as in the evaluation of adrenocortical diseases, diagnosis of Ouoning o cynaremer as ia and adrenal tumors. In hirsute female patients, increased DHEA-S levels have been associated with virilizing adrenal tumors. PHEA with polycystic ovary syndrome have often demonstrated elevated levels of DHEA-S, with persons overal androgen contribution to the defect in this disorder.

The Access DHEA-S Calibrators are intended to calibrate the Access DHEA-S assay The Accoss Drill F O commination of Dehydroepiandrosterone sulfate levels in human serum and plasma using the Access Immunoassay Systems.

Prescription Use

AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 Subpart C)

(Please Do NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Albert C. G.

Page 1 of

Division Sign-Qff

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K040181

§ 862.1245 Dehydroepiandrosterone (free and sulfate) test system.

(a)
Identification. A dehydroepiandrosterone (free and sulfate) test system is a device intended to measure dehydroepiandrosterone (DHEA) and its sulfate in urine, serum, plasma, and amniotic fluid. Dehydroepiandrosterone measurements are used in the diagnosis and treatment of DHEA-secreting adrenal carcinomas.(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.